Meningitis Medscape

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com/article/232915-print
emedicine.medscape.com
Meningitis
Updated: Jul 16, 2019
Author: Rodrigo Hasbun, MD, MPH; Chief Editor: Michael Stuart Bronze, MD
Overview
Practice Essentials
Meningitis is a clinical syndrome characterized by inflammation of the meninges. The image below depicts acute bacterial
meningitis.
Acute bacterial meningitis. This axial nonenhanced computed tomography scan shows mild ventriculomegaly and sulcal
effacement.
Signs and symptoms

The classic triad of bacterial meningitis consists of the following:
Fever
Headache
Neck stiffness
Up to 95% of patients with bacterial meningitis have at least two of the four following symptoms: fever, headache, stiff neck,
or altered mental status.
Other symptoms can include nausea, vomiting, photalgia (photophobia), sleepiness, confusion, irritability, delirium, and
coma. Patients with viral meningitis may have a history of preceding systemic symptoms (eg, myalgias, fatigue, or anorexia).
The history should also address the following:
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Epidemiologic factors and predisposing risks such as mosquito bites (West Nile virus in endemic months, June-
October in the United States)
Exposure to a sick contacts (small children with febrile illness)
Previous medical treatment and existing conditions
Geographic location and travel history
Season and temperature (enterovirus and West Nile virus in the summer and fall; herpes simplex virus type 2 year
round)
Acute bacterial meningitis in otherwise healthy patients who are not at the extremes of age presents in a clinically obvious
fashion; however, subacute bacterial meningitis often poses a diagnostic challenge.
General physical findings in viral meningitis are common to all causative agents. Enteroviral infection is suggested by the
following:
Exanthemas
Contact with small children with febrile illnesses
Symptoms of pericarditis, myocarditis, or conjunctivitis
Syndromes of pleurodynia, herpangina, and hand-foot-and-mouth disease
Infants may have the following:
Bulging fontanelle (if euvolemic)
Paradoxic irritability (ie, remaining quiet when stationary and crying when held)
High-pitched cry
Hypotonia
The examination should evaluate the following:
Focal neurologic signs
Signs of meningeal irritation
Systemic and extracranial findings
Level of consciousness
In chronic meningitis, it is essential to perform careful general, systemic, and neurologic examinations, looking especially for
the following:
Lymphadenopathy
Papilledema
Meningismus
Cranial nerve palsies
Other focal neurological signs
Patients with aseptic meningitis syndrome usually appear clinically nontoxic, with no vascular instability. They
characteristically have an acute onset of meningeal symptoms, fever, and CSF pleocytosis that is usually prominently
lymphocytic.
See Clinical Presentation for more detail.
Diagnosis
The diagnostic challenges in patients with clinical findings of meningitis are as follows:
Early identification and treatment of patients with acute bacterial meningitis
Assessing whether a treatable CNS infection is present in those with suspected subacute or chronic meningitis
Identifying the causative organism
Blood studies that may be useful include the following:
Complete blood count (CBC) with differential
Serum electrolytes
Serum glucose (which is compared with the CSF glucose)
Blood urea nitrogen (BUN) or creatinine and liver profile
In addition, the following tests may be ordered:
Blood, nasopharynx, respiratory secretion, urine or skin lesion cultures or antigen/polymerase chain reaction (PCR)
detection assays
Syphilis testing
Serum procalcitonin testing
Lumbar puncture and CSF analysis
Neuroimaging (CT of the head or MRI of the brain)
See Workup for more detail.
Management
Initial measures include the following:
Shock or hypotension – Crystalloids
Altered mental status – Seizure precautions and treatment (if necessary), along with airway protection (if warranted)
Stable with normal vital signs – Oxygen, IV access, and rapid transport to the emergency department (ED)
Treatment of bacterial meningitis includes the following:
Prompt initiation of empiric antibacterial therapy as appropriate for patient age and condition
After identification of the pathogen and determination of susceptibilities, targeted antibiotic therapy as appropriate for
patient age and condition
Steroid (typically, dexamethasone) therapy
In certain patients, consideration of intrathecal antibiotics
The following systemic complications of acute bacterial meningitis must be treated:
Hypotension or shock
Hypoxemia
Hyponatremia
Cardiac arrhythmias and ischemia
Stroke
Exacerbation of chronic diseases
Most cases of viral meningitis are benign and self-limited, but in certain instances, specific antiviral therapy may be
indicated, if available.
Other types of meningitis are treated with specific therapy as appropriate for the causative pathogen, as follows:
Fungal meningitis - Cryptococcal (amphotericin B, flucytosine, fluconazole), Coccidioides immitis (fluconazole,

amphotericin B, itraconazole), Histoplasma capsulatum (liposomal amphotericin B, itraconazole), or Candida
(amphotericin plus 5-flucytosine)
Tuberculous meningitis (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin)
Parasitic meningitis (amebic [Naegleria fowleri] or acanthamebic) - Variable regimens
Lyme meningitis (ceftriaxone; alternatively, penicillin G, doxycycline, chloramphenicol)
See Treatment and Medication for more detail.
Background
Infections of the central nervous system (CNS) can be divided into 2 broad categories: those primarily involving the
meninges (meningitis; see the image below) and those primarily confined to the parenchyma (encephalitis).
Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.
Meningitis is a clinical syndrome characterized by inflammation of the meninges, the 3 layers of membranes that enclose the
brain and spinal cord. These layers consist of the following:
Dura - A tough outer membrane
Arachnoid - A lacy, weblike middle membrane
Subarachnoid space - A delicate, fibrous inner layer that contains many of the blood vessels that feed the brain and
spinal cord
Risk factors for meningitis include the following:
Extremes of age (< 5 or >60 years)
Diabetes mellitus, chronic kidney failure, adrenal insufficiency, hypoparathyroidism, or cystic fibrosis
Immunosuppression, which increases the risk of opportunistic infections and acute bacterial meningitis
HIV infection, which predisposes to bacterial meningitis caused by encapsulated organisms, primarily Streptococcus
pneumoniae, and opportunistic pathogens
Crowding (such as that experienced by military recruits and college dorm residents), which increases the risk of
outbreaks of meningococcal meningitis
Splenectomy and sickle cell disease, which increase the risk of meningitis secondary to encapsulated organisms
Alcoholism and cirrhosis
Recent exposure to others with meningitis, with or without prophylaxis
Contiguous infection (eg, sinusitis)
Dural defect (eg, traumatic, surgical, or congenital)
Thalassemia major
Intravenous (IV) drug abuse
Bacterial endocarditis
Ventriculoperitoneal shunt
Malignancy (increased risk of Listeria infection)
Some cranial congenital deformities
Clinically, meningitis manifests with meningeal symptoms (eg, headache, nuchal rigidity, or photophobia), as well as
pleocytosis (an increased number of white blood cells [WBCs]) in the cerebrospinal fluid (CSF). Depending on the duration
of symptoms, meningitis may be classified as acute or chronic. (See Etiology and Presentation.)
Anatomically, meningitis can be divided into inflammation of the dura (sometimes referred to as pachymeningitis), which is
less common, and leptomeningitis, which is more common and is defined as inflammation of the arachnoid tissue and
subarachnoid space. (See Anatomy.)
Meningitis can also be divided into the following 3 general categories:
Bacterial (pyogenic)
Granulomatous
Aseptic
The most common cause of meningeal inflammation is bacterial or viral infection. The organisms usually enter the meninges
through the bloodstream from other parts of the body. Most cases of bacterial meningitis are localized over the dorsum of the
brain; however, under certain conditions, meningitis may be concentrated at the base of the brain, as with fungal diseases
and tuberculosis. (See Etiology.)
Bacterial meningitis consists of pyogenic inflammation of the meninges and the underlying subarachnoid CSF. If not treated,
it may lead to lifelong disability or death.[1, 2] Before the antimicrobial era, bacterial meningitis was uniformly fatal, but with
the advent of antimicrobial therapy, the overall mortality from this disease has decreased. Nonetheless, it remains alarmingly
high: approximately 25%. (See Epidemiology.)
The emergence of resistant bacterial strains has prompted changes in antibiotic protocols in some countries, including the
United States. Apart from dexamethasone, neuronal cell protectants still hold only future promise as adjunctive therapy. (See
Treatment and Medication.)
The specific infectious agents that are involved in bacterial meningitis vary among different patient age groups, and the
inflammation may evolve into the following conditions:
Ventriculitis
Empyema
Cerebritis
Abscess formation
Meningitis can also be also classified more specifically according to its etiology. Numerous infectious and noninfectious
causes of meningitis have been identified. Examples of common noninfectious causes include medications (eg, nonsteroidal
anti-inflammatory drugs [NSAIDs] and antibiotics) and carcinomatosis. (See Etiology.)
Bacterial meningitis
Acute bacterial meningitis denotes a bacterial cause of this syndrome. This is usually characterized by an acute onset of
meningeal symptoms and neutrophilic pleocytosis. Depending on the specific bacterial cause, the syndrome may be called,
for example, any of the following:
Pneumococcal meningitis
Haemophilus influenzae meningitis
Staphylococcal meningitis
Meningococcal meningitis
Tuberculous meningitis
Pediatric bacterial meningitis
Chronic meningitis is a constellation of signs and symptoms of meningeal irritation associated with CSF pleocytosis that
persists for longer than 4 weeks.
Unlike subacute (developing over 1-7 days) or chronic (>7 days) meningitis, which have myriad infectious and noninfectious
etiologies, acute meningitis (< 1 day) is almost always a bacterial infection caused by 1 of several organisms. Depending on
age and general condition, these gravely ill patients present acutely with signs and symptoms of meningeal inflammation and
systemic infection of less than 24 hours’ (and usually >12 hours’) duration.
Patients with acute bacterial meningitis may decompensate very quickly. Consequently, they require emergency care,
including the administration of appropriate antimicrobial therapy as soon as possible once bacterial meningitis is suspected
or proven.
Nonbacterial meningitis
Fungal and parasitic forms of meningitis are also named according to their specific etiologic agent (eg, cryptococcal
meningitis, Histoplasma meningitis, and amebic meningoencephalitis).
In many cases, a cause of meningitis is not apparent after initial evaluation, and the disease is therefore classified as aseptic
meningitis. These patients characteristically have an acute onset of meningeal symptoms, fever, and CSF pleocytosis that is
usually prominently lymphocytic.
When the cause of aseptic meningitis is discovered, the disease can be reclassified according to its etiology. If appropriate
diagnostic methods are performed, a specific viral etiology is identified in 55-70% of cases of aseptic meningitis. However,
the condition can also be caused by bacterial, fungal, mycobacterial, and parasitic agents.
If, after an extensive workup, aseptic meningitis is found to have a viral etiology, it can be reclassified as a form of acute viral
meningitis (eg, enteroviral meningitis or herpes simplex virus [HSV] meningitis).
Pathophysiology
Most cases of meningitis are caused by an infectious agent that has colonized or established a localized infection elsewhere
in the host. Potential sites of colonization or infection include the skin, the nasopharynx, the respiratory tract, the
gastrointestinal (GI) tract, and the genitourinary tract. The organism invades the submucosa at these sites by circumventing
host defenses (eg, physical barriers, local immunity, and phagocytes or macrophages).
An infectious agent (ie, a bacterium, virus, fungus, or parasite) can gain access to the CNS and cause meningeal disease
via any of the 3 following major pathways:
Invasion of the bloodstream (ie, bacteremia, viremia, fungemia, or parasitemia) and subsequent hematogenous
seeding of the CNS
A retrograde neuronal (eg, olfactory and peripheral nerves) pathway (eg, Naegleria fowleri or Gnathostoma
spinigerum)
Direct contiguous spread (eg, sinusitis, otitis media, congenital malformations, trauma, or direct inoculation during
intracranial manipulation)
Invasion of the bloodstream and subsequent seeding is the most common mode of spread for most agents. This pathway is
characteristic of meningococcal, cryptococcal, syphilitic, and pneumococcal meningitis.
Rarely, meningitis arises from invasion via septic thrombi or osteomyelitic erosion from infected contiguous structures.
Meningeal seeding may also occur with a direct bacterial inoculate during trauma, neurosurgery, or instrumentation.
Meningitis in the newborn may be transmitted vertically, involving pathogens that have colonized the maternal intestinal or
genital tract, or horizontally, from nursery personnel or caregivers at home.
Local extension from contiguous extracerebral infection (eg, otitis media, mastoiditis, or sinusitis) is a common cause.
Possible pathways for the migration of pathogens from the middle ear to the meninges include the following:
The bloodstream
Preformed tissue planes (eg, posterior fossa)
Temporal bone fractures
The oval or round window membranes of the labyrinths
The brain is naturally protected from the body’s immune system by the barrier that the meninges create between the
bloodstream and the brain. Normally, this protection is an advantage because the barrier prevents the immune system from
attacking the brain. However, in meningitis, the blood-brain barrier can become disrupted; once bacteria or other organisms
have found their way to the brain, they are somewhat isolated from the immune system and can spread.
When the body tries to fight the infection, the problem can worsen; blood vessels become leaky and allow fluid, WBCs, and
other infection-fighting particles to enter the meninges and brain. This process, in turn, causes brain swelling and can
eventually result in decreasing blood flow to parts of the brain, worsening the symptoms of infection.[3]
Depending on the severity of bacterial meningitis, the inflammatory process may remain confined to the subarachnoid space.
In less severe forms, the pial barrier is not penetrated, and the underlying parenchyma remains intact. However, in more
severe forms of bacterial meningitis, the pial barrier is breached, and the underlying parenchyma is invaded by the
inflammatory process. Thus, bacterial meningitis may lead to widespread cortical destruction, particularly when left
untreated.
Replicating bacteria, increasing numbers of inflammatory cells, cytokine-induced disruptions in membrane transport, and
increased vascular and membrane permeability perpetuate the infectious process in bacterial meningitis. These processes
account for the characteristic changes in CSF cell count, pH, lactate, protein, and glucose in patients with this disease.
Exudates extend throughout the CSF, particularly to the basal cisterns, resulting in the following:
Damage to cranial nerves (eg, cranial nerve VIII, with resultant hearing loss)
Obliteration of CSF pathways (causing obstructive hydrocephalus)
Induction of vasculitis and thrombophlebitis (causing local brain ischemia)
Intracranial pressure and cerebral fluid

One complication of meningitis is the development of increased intracranial pressure (ICP). The pathophysiology of this
complication is complex and may involve many proinflammatory molecules as well as mechanical elements. Interstitial
edema (secondary to obstruction of CSF flow, as in hydrocephalus), cytotoxic edema (swelling of cellular elements of the
brain through the release of toxic factors from the bacteria and neutrophils), and vasogenic edema (increased blood brain
barrier permeability) are all thought to play a role.
Without medical intervention, the cycle of decreasing CSF, worsening cerebral edema, and increasing ICP proceeds
unchecked. Ongoing endothelial injury may result in vasospasm and thrombosis, further compromising CSF, and may lead to
stenosis of large and small vessels. Systemic hypotension (septic shock) also may impair CSF, and the patient soon dies as
a consequence of systemic complications or diffuse CNS ischemic injury.
Cerebral edema
The increased CSF viscosity resulting from the influx of plasma components into the subarachnoid space and diminished
venous outflow lead to interstitial edema. The accumulation of the products of bacterial degradation, neutrophils, and other
cellular activation leads to cytotoxic edema.
The ensuing cerebral edema (ie, vasogenic, cytotoxic, and interstitial) significantly contributes to intracranial hypertension
and a consequent decrease in cerebral blood flow. Anaerobic metabolism ensues, which contributes to increased lactate
concentration and hypoglycorrhachia. In addition, hypoglycorrhachia results from decreased glucose transport into the spinal
fluid compartment. Eventually, if this uncontrolled process is not modulated by effective treatment, transient neuronal
dysfunction or permanent neuronal injury results.
Cytokines and secondary mediators in bacterial meningitis
Key advances in understanding the pathophysiology of meningitis include insight into the pivotal roles of cytokines (eg,
tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1), chemokines (IL-8), and other proinflammatory molecules in the
pathogenesis of pleocytosis and neuronal damage during occurrences of bacterial meningitis.
Increased CSF concentrations of TNF-α, IL-1, IL-6, and IL-8 are characteristic findings in patients with bacterial meningitis.
Cytokine levels, including those of IL-6, TNF-α, and interferon gamma, have been found to be elevated in patients with
aseptic meningitis.
The proposed events involving these inflammation mediators in bacterial meningitis begin with the exposure of cells (eg,
endothelial cells, leukocytes, microglia, astrocytes, and meningeal macrophages) to bacterial products released during
replication and death; this exposure incites the synthesis of cytokines and proinflammatory mediators. This process is likely
initiated by the ligation of the bacterial components (eg, peptidoglycan and lipopolysaccharide) to pattern-recognition
receptors, such as the Toll-like receptors (TLRs).
TNF-α and IL-1 are most prominent among the cytokines that mediate this inflammatory cascade. TNF-α is a glycoprotein
derived from activated monocyte-macrophages, lymphocytes, astrocytes, and microglial cells.
IL-1, previously known as endogenous pyrogen, is also produced primarily by activated mononuclear phagocytes and is
responsible for the induction of fever during bacterial infections. Both IL-1 and TNF-α have been detected in the CSF of
individuals with bacterial meningitis. In experimental models of meningitis, they appear early during the course of disease
and have been detected within 30-45 minutes of intracisternal endotoxin inoculation.
Many secondary mediators, such as IL-6, IL-8, nitric oxide, prostaglandins (eg, prostaglandin E2 [PGE2]), and platelet
activation factor (PAF), are presumed to amplify this inflammatory event, either synergistically or independently. IL-6 induces
acute-phase reactants in response to bacterial infection. The chemokine IL-8 mediates neutrophil chemoattractant
responses induced by TNF-α and IL-1.
Nitric oxide is a free radical molecule that can induce cytotoxicity when produced in high amounts. PGE2, a product of
cyclooxygenase (COX), appears to participate in the induction of increased blood-brain barrier permeability. PAF, with its
myriad biologic activities, is believed to mediate the formation of thrombi and the activation of clotting factors within the
vasculature. However, the precise roles of all these secondary mediators in meningeal inflammation remain unclear.
The net result of the above processes is vascular endothelial injury and increased blood-brain barrier permeability, leading to
the entry of many blood components into the subarachnoid space. In many cases, this contributes to vasogenic edema and
elevated CSF protein levels. In response to the cytokines and chemotactic molecules, neutrophils migrate from the
bloodstream and penetrate the damaged blood-brain barrier, producing the profound neutrophilic pleocytosis characteristic
of bacterial meningitis.
Genetic predisposition to inflammatory response
The inflammatory response and the release of proinflammatory mediators are critical to the recruitment of excess neutrophils
to the subarachnoid space. These activated neutrophils release cytotoxic agents, including oxidants and metalloproteins that
cause collateral damage to brain tissue.
Pattern recognition receptors, of which TLR A4 (TLRA4) is the best studied, lead to increase in the myeloid differentiation 88
(MyD88)-dependent pathway and excess production of proinflammatory mediators. At present, dexamethasone is used to
decrease the effects of cellular toxicity by neutrophils after they are present. Researchers are actively seeking ways of
inhibiting TLRA4 and other proinflammatory recognition receptors through genetically engineered suppressors.[4]
Bacterial seeding
Bacterial seeding of the meninges usually occurs through hematogenous spread. In patients without an identifiable source of
infection, local tissue and bloodstream invasion by bacteria that have colonized the nasopharynx may be a common source.
Many meningitis-causing bacteria are carried in the nose and throat, often asymptomatically. Most meningeal pathogens are
transmitted through the respiratory route, including Neisseria meningitidis (meningococcus) and S pneumoniae
(pneumococcus).
Certain respiratory viruses are thought to enhance the entry of bacterial agents into the intravascular compartment,
presumably by damaging mucosal defenses. Once in the bloodstream, the infectious agent must escape immune
surveillance (eg, antibodies, complement-mediated bacterial killing, and neutrophil phagocytosis).
Subsequently, hematogenous seeding into distant sites, including the CNS, occurs. The specific pathophysiologic
mechanisms by which the infectious agents gain access to the subarachnoid space remain unclear. Once inside the CNS,
the infectious agents likely survive because host defenses (eg, immunoglobulins, neutrophils, and complement components)
appear to be limited in this body compartment. The presence and replication of infectious agents remain uncontrolled and
incite the cascade of meningeal inflammation described above.
Etiology
Causes of meningitis include bacteria, viruses, fungi, parasites, and drugs (eg, NSAIDs, metronidazole, and IV
immunoglobulin [IVIg]). Certain risk factors are associated with particular pathogens.
HIV infection increases susceptibility to meningitis from a variety of pathogens, including cryptococci, Mycobacterium
tuberculosis, syphilis, cytomegalovirus, varicella zoster virus, and Listeria species. In addition, HIV itself may cause aseptic
meningitis (see Meningitis in HIV).
Other viral causes of meningitis include the following:
Enteroviruses
West Nile virus
Human herpesvirus (HHV)-2
Lymphocytic choriomeningitis virus (LCM)
In patients who have had trauma or neurosurgery, the most common microorganisms are S pneumoniae (if CSF leak is
present), Staphylococcus aureus, enterobacteria, and Pseudomonas aeruginosa. In patients with an infected
ventriculoperitoneal (atrial) shunt, the most common microorganisms are Staphylococcus epidermidis, S aureus,
enterobacteria, Propionibacterium acnes, and diphtheroids (rare). Consultation with a neurosurgeon is indicated; early shunt
removal is usually necessary for cure.
Pachymeningitis
As indicated by the presence of abundant pus, pachymeningitis most often results from a bacterial infection (usually
staphylococcal or streptococcal) that is localized to the dura. The organisms most often gain access to the meninges via a
skull defect (eg, a skull fracture) or spread from an infection of the paranasal sinuses or cranial osteomyelitis.
Haemophilus influenzaemeningitis
H influenzae is a small, pleomorphic, gram-negative coccobacillus that is frequently found as part of the normal flora in the
upper respiratory tract. The organism can spread from one individual to another in airborne droplets or by direct contact with
secretions. Meningitis is the most serious acute manifestation of systemic infection with H influenzae. (See Haemophilus
Meningitis.)
In the past, H influenzae was a major cause of meningitis, and the encapsulated type b strain of the organism (Hib)
accounted for the majority of cases. Since the introduction of Hib vaccine in the United States in 1990, the overall incidence
of H influenzae meningitis has decreased by 35%, with Hib accounting for fewer than 9.4% of H influenzae cases.[5]
The isolation of H influenzae in adults suggests the presence of an underlying medical disorder, such as the following:
Paranasal sinusitis
Otitis media
Alcoholism
CSF leak after head trauma
Functional or anatomic asplenia
Hypogammaglobulinemia
Pneumococcal meningitis
S pneumoniae, a gram-positive coccus, is the most common bacterial cause of meningitis. In addition, it is the most common
bacterial agent in meningitis associated with basilar skull fracture and CSF leak. It may be associated with other focal
infections, such as pneumonia, sinusitis, or endocarditis (as, for example, in Austrian syndrome, which is the triad of
pneumococcal meningitis, endocarditis, and pneumonia).
S pneumoniae is a common colonizer of the human nasopharynx; it is present in 5-10% of healthy adults and 20-40% of
healthy children. It causes meningitis by escaping local host defenses and phagocytic mechanisms, either through choroid
plexus seeding from bacteremia or through direct extension from sinusitis or otitis media.
Patients with the following conditions are at increased risk for S pneumoniae meningitis:
Hyposplenism
Hypogammaglobulinemia
Multiple myeloma
Glucocorticoid treatment
Defective complement (C1-C4)
Diabetes mellitus
Renal insufficiency
Alcoholism
Malnutrition
Chronic liver disease
Streptococcus agalactiae meningitis

Streptococcus agalactiae (group B streptococcus [GBS]) is a gram-positive coccus that inhabits the lower GI tract. It also
colonizes the female genital tract at a rate of 5-40%, which explains why it is the most common agent of neonatal meningitis
(associated with 70% of cases).
Predisposing risks in adults include the following:
Diabetes mellitus
Pregnancy
Alcoholism
Hepatic failure
Renal failure
Corticosteroid treatment
In 43% of adult cases, however, no underlying disease is present.
Meningococcal meningitis
N meningitidis is a gram-negative diplococcus that is carried in the nasopharynx of otherwise healthy individuals. It initiates
invasion by penetrating the airway epithelial surface. The precise mechanism by which this occurs is unclear, but recent viral
or mycoplasmal infection has been reported to disrupt the epithelial surface and facilitate invasion by meningococcus.
Most sporadic cases of meningococcal meningitis (95-97%) are caused by serogroups B, C, and Y, whereas the A and C
strains are observed in epidemics (< 3% of cases). Currently, N meningitidis is one of the leading cause of bacterial
meningitis in children and young adults, but the incidence has decreased with use of the conjugate meningococcal vaccine.
[6]
Risk factors for meningococcal meningitis include the following:
Deficiencies in terminal complement components (eg, membrane attack complex, C5-C9), which increases attack
rates but is associated with surprisingly lower mortality rates
Properdin defects that increase the risk of invasive disease
Antecedent viral infection, chronic medical illness, corticosteroid use, and active or passive smoking
Crowded living conditions, as is observed in college dormitories (college freshmen living in dormitories are at highest
risk) and military facilities, which has been reported in clustering of cases
Listeria monocytogenes meningitis
Listeria monocytogenes is a small gram-positive bacillus that causes 3% of bacterial meningitis cases and is associated with
one of the highest mortalities (20%).[5] The organism is widespread in nature and has been isolated in the stool of 5% of
healthy adults. Most human cases appear to be food-borne.
L monocytogenes is a common food contaminant, with a recovery rate of up to 70% from raw meat, vegetables, and meats.
Outbreaks have been associated with consumption of contaminated coleslaw, milk, cheese, and alfalfa tablets.
Groups at risk include the following:
Pregnant women
Infants and children
Elderly individuals (>60 years)
Patients with alcoholism
Adults who are immunosuppressed (eg, steroid users, transplant recipients, or persons with AIDS)
Individuals with chronic liver and renal disease
Individuals with diabetes
Persons with iron-overload conditions (eg, hemochromatosis or transfusion-induced iron overload)
Meningitis caused by gram-negative bacilli
Aerobic gram-negative bacilli include the following:
Escherichia coli
Klebsiella pneumoniae
Serratia marcescens
P aeruginosa
Salmonella species
Gram-negative bacilli can cause meningitis in certain groups of patients. E coli is a common agent of meningitis among
neonates. Other predisposing risk factors for meningitis associated with gram-negative bacilli include the following:
Neurosurgical procedures or intracranial manipulation
Old age
Immunosuppression
High-grade gram-negative bacillary bacteremia
Disseminated strongyloidiasis
Disseminated strongyloidiasis has been reported as a classic cause of gram-negative bacillary bacteremia, as a result of the
translocation of gut microflora with the Strongyloides stercoralis larvae during hyperinfection syndrome.
Staphylococcal meningitis
Staphylococci are gram-positive cocci that are part of the normal skin flora. Meningitis caused by staphylococci is associated
with the following risk factors:
Neurosurgery
Head trauma
Presence of CSF shunts
Infective endocarditis and paraspinal infection
S epidermidis is the most common cause of meningitis in patients with CNS (ie, ventriculoperitoneal) shunts. (See
Staphylococcal Meningitis.)
Aseptic meningitis
Aseptic meningitis is one of the most common infections of the meninges. Unfortunately, up to 86% of cases of aseptic
meningitis in adults have unknown causes, since molecular diagnostic techniques and arboviral serologies are underutilized.
[7] If appropriate diagnostic methods are employed, a specific viral etiology is identified in 50-60% of cases of aseptic
meningitis. However, aseptic meningitis can also be caused by bacteria, fungi, and parasites (see Table 1 below). It is
noteworthy that partially treated bacterial meningitis accounts for a large number of meningitis cases with a negative
microbiologic workup.
Table 1. Infectious Agents Causing Aseptic Meningitis (Open Table in a new window)
Category Agent
Bacteria Partially treated bacterial meningitis
Listeria monocytogenes
Brucella spp
Rickettsia rickettsii
Ehrlichia spp
Mycoplasma pneumoniae
Borrelia burgdorferi
Treponema pallidum
Leptospira spp
Mycobacterium tuberculosis
Nocardia spp
Naegleria fowleri
Acanthamoeba spp
Balamuthia spp
Angiostrongylus cantonensis
Parasites
Gnathostoma spinigerum
Baylisascaris procyonis
Strongyloides stercoralis
Taenia solium (cysticercosis)
Cryptococcus neoformans
Coccidioides immitis
Blastomyces dermatitidis
Fungi
Histoplasma capsulatum
Candida spp
Aspergillus spp
Viruses Poliovirus
Echovirus
Enterovirus Coxsackievirus A
Coxsackievirus B
Enterovirus 68-71
HSV-1 and HSV-2
Varicella-zoster virus
Herpesvirus (HSV) Epstein-Barr virus
Cytomegalovirus
HHV-6 and HHV-7
Mumps virus
Paramyxovirus
Measles virus
Togavirus Rubella virus
Flavivirus West Nile virus
Japanese encephalitis virus
St Louis encephalitis virus
California encephalitis virus

Bunyavirus
La Crosse encephalitis virus
Eastern equine encephalitis virus
Alphavirus Western equine encephalitis virus
Venezuelan encephalitis virus
Reovirus Colorado tick fever virus
Arenavirus LCM virus
Rhabdovirus Rabies virus
Retrovirus HIV
HHV = human herpesvirus; HSV = herpes simplex virus; LCM = lymphocytic choriomeningitis.
Enteroviruses account for of the majority of cases of aseptic meningitis in children, but West Nile virus and HSV-2 account
for a substantial proportion of cases in adults. The enteroviruses belong to the family Picornaviridae and are further
classified as follows:
Poliovirus (3 serotypes)
Coxsackievirus A (23 serotypes)
Coxsackievirus B (6 serotypes)
Echovirus (31 serotypes)
Newly recognized enterovirus serotypes 68-71
Enteroviruses are usually spread by fecal-oral or respiratory routes. Infection occurs during summer and fall in temperate
climates and year-round in tropical regions.
The nonpolio enteroviruses (NPEVs) account for approximately 90% of cases of viral meningitis in which a specific pathogen
can be identified.
Echovirus 30 was reported as the cause of an epidemic in Japan in 1991. It was also reported as the cause of 20% of cases
of aseptic meningitis reported to the Centers for Disease Control and Prevention (CDC) in 1991.
The Herpesviridae family consists of large, DNA-containing enveloped viruses. Eight members are known to cause human
infections, and all have been implicated in meningitis syndromes, with the exception of HHV-8 or Kaposi sarcoma–
associated virus.
HSV accounts for 0.5-3% of cases of aseptic meningitis; it is most commonly associated with primary genital infection and is
less likely during recurrences. HSV-1 is a cause of encephalitis, while HSV-2 more commonly causes meningitis. Although
Mollaret syndrome (a recurrent, but benign, aseptic meningitis syndrome) is more frequently associated with HSV-2, HSV-1
has also been implicated as a cause.
Epstein-Barr virus (EBV, or HHV-4) and cytomegalovirus (CMV, or HHV-5) infection may manifest as meningitis in patients
with the mononucleosis syndrome. Varicella-zoster virus (VZV, or HHV-3) and CMV cause meningitis in
immunocompromised hosts, especially patients with AIDS and transplant recipients. HHV-6 and HHV-7 have been reported
to cause meningitis in transplant recipients.
The most common arthropod-borne viruses are West Nile virus, St Louis encephalitis virus (a flavivirus), Colorado tick fever
virus, and California encephalitis virus (bunyavirus group, including La Crosse encephalitis virus). St Louis encephalitis virus
is a mosquito-borne flavivirus that may cause a febrile syndrome, aseptic meningitis syndrome, and encephalitis. Other
members of the flavivirus group that may cause aseptic meningitis include tick-borne encephalitis virus, Powassan
encephalitis, and Japanese encephalitis virus. Toscana virus is one of the most common causes of aseptic meningitis in the
Mediterranean and is transmitted by a sandfly.[8]
California encephalitis is a common childhood disease of the CNS that is caused by a virus in the genus Bunyavirus. Most of
the cases of California encephalitis are probably caused by mosquito-borne La Crosse encephalitis virus.
LCM virus is a member of the arenaviruses, a family of single-stranded, RNA-containing viruses in which rodents are the
animal reservoir. The modes of transmission include aerosols and direct contact with rodents. Outbreaks have also been
traced to infected laboratory mice and hamsters.
The mumps virus is the most common cause of aseptic meningitis in unimmunized populations, occurring in 30% of all
patients with mumps. Upon exposure, an incubation period of approximately 5-10 days ensues, followed by a nonspecific
febrile illness and an acute onset of aseptic meningitis. This may be associated with orchitis, arthritis, myocarditis, and
alopecia.
Patients with acute HIV infection may present with aseptic meningitis syndrome, usually as part of the mononucleosislike
acute seroconversion phenomenon. HIV should always be suspected as a cause of aseptic meningitis in a patient with risk
factors such as IV drug use or high-risk sexual behaviors. These patients will have negative results on HIV serologic tests
(eg, enzyme-linked immunosorbent assay [ELISA] and Western blot); the diagnosis is made by the detection of serum HIV
RNA on polymerase chain reaction (PCR) testing or of HIV p24 antigen.
Adenovirus (serotypes 1, 6, 7, and 12) has been associated with cases of meningoencephalitis. Chronic
meningoencephalitis has been reported with serotypes 7, 12, and 32. The infection is usually acquired through a respiratory
route.
Toscana virus meningitis or encephalitis should be considered in travelers returning from the a Mediterranean country (eg,
Italy, Spain, or Greece) during the summer. Toscana viruses are transmitted by the bite of a sandfly. Toscana virus infection
can be diagnosed by performing paired serologies and CSF PCR, which in the United States is available only through the
CDC.[9]
Chronic meningitis
Chronic meningitis can be caused by a wide range of infectious and noninfectious etiologies (see Table 2 below).
Table 2. Causes of Chronic Meningitis (Open Table in a new window)
Category Agent
Bacteria Mycobacterium tuberculosis
Borrelia burgdorferi
Treponema pallidum
Brucella spp
Francisella tularensis
Nocardia spp
Actinomyces spp
Cryptococcus neoformans
Blastomyces dermatitidis
Fungi Histoplasma capsulatum
Candida albicans
Aspergillus spp
Sporothrix schenckii
Acanthamoeba spp
Naegleria fowleri
Angiostrongylus cantonensis
Gnathostoma spinigerum
Parasites
Baylisascarisprocyonis
Schistosoma spp
Strongyloides stercoralis
Echinococcus granulosus
Brucellae are small gram-negative coccobacilli that cause zoonoses as a result of infection with Brucella abortus, Brucella
melitensis, Brucella suis, or Brucella canis. Transmission to humans occurs after direct or indirect exposure to infected
animals (eg, sheep, goats, or cattle). Direct infection of the CNS occurs in fewer than 5% of cases, with most patients
presenting with acute or chronic meningitis.
Persons at risk for brucellosis include individuals who had contact with infected animals or their products (eg, through intake
of unpasteurized milk products). Veterinarians, abattoir workers, and laboratory workers dealing with these animals are also
at risk.
M tuberculosis is an acid-fast bacillus that causes a broad range of clinical illnesses that can affect virtually any organ of the
body. It is spread through airborne droplet nuclei, and it infects one third of the world’s population. Involvement of the CNS
with tuberculous meningitis is usually caused by rupture of a tubercle into the subarachnoid space.
Tuberculous meningitis should always be considered in the differential diagnosis of patients with aseptic meningitis or
chronic meningitis syndromes, especially those with basilar meningitis, symptoms of more than 5 days’ duration, or cranial
nerve palsies. If tuberculous meningitis is suspected, antituberculosis therapy, with or without steroids, should be empirically
started.
Treponema pallidum is a slender, tightly coiled spirochete that is usually acquired by sexual contact. Other modes of
transmission include direct contact with an active lesion, passage through the placenta, and blood transfusion (rare).
Borrelia burgdorferi, a tick-borne spirochete, is the agent of Lyme disease, the most common vector-borne disease in the
United States. Meningitis may be part of a triad of neurologic manifestations of Lyme disease that also includes cranial
neuritis and radiculoneuritis. Lyme disease meningitis is typically associated with a facial palsy that can sometimes be
bilateral.
Cryptococcus neoformans is an encapsulated, yeastlike fungus that is ubiquitous. It has been found in high concentrations in
aged pigeon droppings and pigeon nesting places. The 4 serotypes are designated A through D, with the A serotype causing
most human infections. Onset of cryptococcal meningitis may be acute, especially among patients with AIDS.
Numerous cases occur in healthy hosts (eg, persons with no known T-cell defect); however, approximately 50-80% of cases
occur in immunocompromised hosts. At particular risk are individuals with defects of T-cell–mediated immunity, such as
persons with AIDS, organ transplant recipients, and other patients who use steroids, cyclosporine, and other
immunosuppressants. Cryptococcal meningitis has also been reported in patients with idiopathic CD-4 lymphopenia,
Hodgkin disease, sarcoidosis, and cirrhosis.
Coccidioides immitis is a soil-based, dimorphic fungus that exists in mycelial and yeast (spherule) forms. Persons at risk for
coccidioidal meningitis include individuals exposed to the endemic regions (eg, tourists and local populations) and those with
immune deficiency (eg, persons with AIDS and organ transplant recipients).
Blastomyces dermatitidis is a dimorphic fungus that has been reported to be endemic in North America (eg, in the
Mississippi and Ohio River basins). It has also been isolated from parts of Central America, South America, the Middle East,
and India. Its natural habitat is not well defined. Soil that is rich in decaying matter and environments around riverbanks and
waterways have been demonstrated to harbor B dermatitidis during outbreaks and are thought to be risk factors for acquiring
the infection.
Inhalation of the conidia establishes a pulmonary infection. Dissemination may occur in certain individuals, including those
with underlying immune deficiency (eg, from HIV or pharmaceutical agents) and extremes of age, and may involve the skin,
bones and joints, genitourinary tract, and CNS. Involvement of the CNS occurs in fewer than 5% of cases.
Histoplasma capsulatum is one of the dimorphic fungi that exist in mycelial and yeast forms. It is usually found in soil and
can occasionally cause a chronic meningitis. The preferred means of making the diagnosis is CSF histoplasma antigen
detection.
Candida species are ubiquitous in nature. They are normal commensals in humans and are found in the skin, the GI tract,
and the female genital tract. The most common species is Candida albicans, but the incidence of non-albicans candidal
infections (eg, Candida tropicalis) is increasing, including species with antifungal resistance (eg, Candida krusei and
Candida glabrata).
Involvement of the CNS usually follows hematogenous dissemination. The most important predisposing risks for acquiring
disseminated candidal infection appear to be iatrogenic (eg, the administration of broad-spectrum antibiotics and the use of
indwelling devices such as urinary and vascular catheters). Prematurity in neonates is considered a predisposing risk factor
as well. Infection may also follow neurosurgical procedures, such as placement of ventricular shunts.
Sporothrix schenckii is an endemic dimorphic fungus that is often isolated from soil, plants, and plant products. Human
infections are characteristically lymphocutaneous. Extracutaneous manifestations of sporotrichosis may occur, though
meningeal sporotrichosis, which is the most severe form, is a rare complication. AIDS is a reported underlying risk factor in
many described cases and is associated with a poor outcome.
Infection with free-living amebas is an infrequent but often life-threatening human illness, even in immunocompetent
individuals. N fowleri is the only species of Naegleria recognized to be pathogenic in humans, and it is the agent of primary
amebic meningoencephalitis (PAM). The parasite has been isolated in lakes, pools, ponds, rivers, tap water, and soil.
Infection occurs when a person is swimming or playing in contaminated water sources (eg, inadequately chlorinated water
and sources associated with poor decontamination techniques). The N fowleri amebas invade the CNS through the nasal
mucosa and cribriform plate.
PAM occurs in 2 forms. The first is characterized by an acute onset of high fever, photophobia, headache, and altered
mental status, similar to bacterial meningitis, occurring within 1 week after exposure. Because it is acquired via the nasal
area, olfactory nerve involvement may manifest as abnormal smell sensation. Death occurs in 3 days in patients who are not
treated. The second form, the subacute or chronic form, consists of an insidious onset of low-grade fever, headache, and
focal neurologic signs. Duration of illness is weeks to few months.
Acanthamoeba and Balamuthia cause granulomatous amebic encephalitis, which is a subacute opportunistic infection that
spreads hematogenously from the primary site of infection (skin or lungs) to the CNS and causes an encephalitis syndrome.
These cases can be difficult to distinguish from culture-negative meningitis.
Angiostrongylus cantonensis, the rat lungworm, can cause eosinophilic meningitis (pleocytosis with more than 10%
eosinophils) in humans. The adult parasite resides in the lungs of rats. Its eggs hatch, and the larval stages are expelled in
the feces. The larvae develop in the intermediate host, usually land snails, freshwater prawns, and crabs. Humans acquire
the infection by ingesting raw mollusks.
Gnathostoma spinigerum, a GI parasite of wild and domestic dogs and cats, may cause eosinophilic meningoencephalitis.
Humans acquire the infection after ingesting undercooked infected fish and poultry.
Baylisascaris procyonis is an ascarid parasite that is prevalent in the raccoon populations in the United States and rarely
causes human eosinophilic meningoencephalitis. Human infections occur after accidental ingestion of food products
contaminated with raccoon feces.
Additional causes of meningitis
Congenital malformation of the stapedial footplate has been implicated in the development of meningitis. Head and neck
surgery, penetrating head injury, comminuted skull fracture, and osteomyelitic erosion may infrequently result in direct
implantation of bacteria into the meninges. Skull fractures can tear the dura and cause a CSF fistula, especially in the region
of the frontal ethmoid sinuses. Patients with any of these conditions are at risk for bacterial meningitis.
Epidemiology
The incidence of meningitis varies according to the specific etiologic agent, as well as in conjunction with a nation’s medical
resources. The incidence is presumed to be higher in developing countries because of less access to preventive services,
such as vaccination. In these countries, the incidence has been reported to be 10 times higher than that in developed
countries.
Meningitis affects people of all races. In the United States, black people have a higher reported rate of meningitis than white
people and Hispanic people.
Epidemiology of bacterial meningitis
With almost 4100 cases and 500 deaths occurring annually in the United States, bacterial meningitis continues to be a
significant source of morbidity and mortality. The annual incidence in the United States is 1.33 cases per 100,000 population.
[5]
Meningococcal meningitis was endemic in parts of Africa, with periodic epidemics occurring in the so-called sub-Saharan
“meningitis belt,” as well as among religious pilgrims traveling to Saudi Arabia for the Hajj. The introduction of the
MenAfriVac (Serum Institute of India Ltd, Hadapsur, Pune, India), a conjugate vaccine against serogroup A N meningitidis, in
sub-Saharan Africa has now eliminated group A meningococcal meningitis outbreaks, but new epidemics are now occurring
with serogroup W and C.[10]
The incidence of neonatal bacterial meningitis is 0.25-1 case per 1000 live births. In addition, the incidence is 0.15 case per
1000 full-term births and 2.5 cases per 1000 premature births. Approximately 30% of newborns with clinical sepsis have
associated bacterial meningitis.
N meningitidis causes approximately 4 cases per 100,000 children aged 1-23 months. The risk of secondary meningitis is
1% for family contacts and 0.1% for daycare contacts. The rate of meningitis caused by S pneumoniae is 6.5 cases per
100,000 children aged 1-23 months.
Previously, Hib, N meningitidis, and S pneumoniae accounted for more than 80% of cases of bacterial meningitis. Since the
late 20th century, however, the epidemiology of bacterial meningitis has been substantially changed by multiple
developments.
The overall incidence of bacterial meningitis in the US declined from 2.0 to 1.38 cases per 100,000 population between 1998
and 2007.[5] This was partially because of the widespread use of the Hib vaccination, which decreased the incidence of H
influenzae meningitis by more than 90% (see Table 3 below). Routine Hib vaccination has nearly eliminating this pathogen
as a cause of meningitis in many developed countries.
More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women
for GBS have further changed the epidemiology of bacterial meningitis.
Table 3. Changing Epidemiology of Acute Bacterial Meningitis in United States* (Open Table in a new window)
Bacteria 1978-1981 1986 1995 1998-2007
Haemophilus influenzae 48% 45% 7% 6.7%
Listeria monocytogenes 2% 3% 8% 3.4%
Neisseria meningitidis 20% 14% 25% 13.9%
Streptococcus agalactiae (group B streptococcus) 3% 6% 12% 18.1%
Streptococcus pneumoniae 13% 18% 47% 58%
*Nosocomial meningitis is not included; these data include only the 5 major meningeal pathogens.
The number of cases of invasive H influenzae disease among children younger than 5 years that were reported to the CDC
declined from 20,000 in 1987 to 255 in 1998. This shift has reportedly been less dramatic in developing countries, where the
use of Hib vaccine is not as widespread.
Because the frequency of bacterial meningitis in children has declined, the condition is becoming more of a disease of
adults. Whereas the median age for persons with bacterial meningitis was 25 years in 1998, it was 15 months in 1986.[11]
The introduction of vaccines against S pneumoniae has substantially reduced the incidence of pneumococcal meningitis in
children. Routine screening for GBS in pregnant women may have also reduced the incidence of meningitis from this
pathogen. Routine vaccination against serogroup C meningococcus may also reduce the incidence of N meningitidis
infections. During a 1998-2007 survey, the incidence of meningitis declined by 31%,[5] a decrease that can be credited to
vaccination programs.
Newborns are at highest risk for acute bacterial meningitis. After the first month of life, the peak incidence is in infants aged
3-8 months. In addition, the incidence is increased in persons aged 60 years and older, independent of other factors. The
annual incidence ranges from 1.7 to 7.2 cases per 100,000 adults; the mean annual incidence has been reported as 3.8
cases per 100,000 adults. Of patients with bacterial meningitis, 61% had no previous or present accompanying diseases that
may have predisposed them to meningitis.
Depending on their age, individuals are also predisposed to meningitis from other etiologic agents (see Table 4 below). E coli
K1 meningitis and S agalactiae meningitis are common among neonates, and L monocytogenes meningitis is common
among neonates and the elderly. (The development of neonatal meningitis is related to labor and delivery; it results from
colonized pathogens in the maternal intestinal or genital tract, immaturity, and environment.)
Table 4. Most Common Bacterial Pathogens on Basis of Age and Predisposing Risks (Open Table in a new window)
Risk or Predisposing Factor Bacterial Pathogen
Streptococcus agalactiae (GBS)
Age 0-4 weeks Escherichia coli K1
Listeria monocytogenes
S agalactiae
E coli
Age 4-12 weeks Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitidis
Age 3 months to 18 years N meningitidis
S pneumoniae
H influenzae
S pneumoniae
Age 18-50 years N meningitidis
H influenzae
S pneumoniae
N meningitidis
Age >50 years
L monocytogenes
Aerobic gram-negative bacilli
S pneumoniae
N meningitidis
Immunocompromised state
L monocytogenes
Staphylococcus aureus
Intracranial manipulation, including neurosurgery Coagulase-negative staphylococci
Aerobic gram-negative bacilli, including Pseudomonas aeruginosa
S pneumoniae
Basilar skull fracture H influenzae
Group A streptococci
Coagulase-negative staphylococci
S aureus
CSF shunts
Propionibacterium acnes
CSF = cerebrospinal fluid; GBS = group B streptococcus.
The reported attack rate for bacterial meningitis is 3.3 male cases per 100,000 population, compared with 2.6 female cases
per 100,000 population. However, in meningitis caused by the mumps virus, males and females are affected equally. In
neonates, the male-to-female ratio is 3:1.
Epidemiology of specific bacterial pathogens of acute meningitis
H influenzae meningitis primarily affects infants younger than 2 years. S agalactiae meningitis occurs principally during the
first 12 weeks of life but has also been reported in adults, primarily affecting individuals older than age 60 years. The overall
case-fatality rate in adults is 34%. Among the bacterial agents that cause meningitis, S pneumoniae is associated with one
of the highest mortalities (19-26%).
Epidemiology of aseptic meningitis
Aseptic meningitis has a reported incidence of 10.9 cases per 100,000 person-years. It occurs in individuals of all ages but is
more common in children, especially during summer. No racial differences are reported.
Viruses are the major cause of aseptic meningitis. The enteroviruses are distributed worldwide, and the infection rates vary
according to the season of the year and a population’s age and socioeconomic status. Most enteroviral infections occur in
individuals who are younger than 15 years, with the highest attack rates in children who are younger than 1 year.
Arboviruses are an important cause of aseptic meningitis and encephalitis in the summer and fall months in the United
States. West Nile virus was introduced to the United States in 1999 and has now spread throughout the continent. In 2012,
the largest outbreak of West Nile virus infection to date occurred in the United States, with 5387 cases reported (about half
of which were neuroinvasive disease, such as meningitis or encephalitis) and a 4.5% mortality.[12] West Nile virus can also
cause acute flaccid paralysis, retinitis and nephropathy.
Other less common arboviruses include St Louis encephalitis virus, Jamestown canyon virus, La Crosse encephalitis virus,
Powassan encephalitis virus, and Eastern equine encephalitis virus. In the United States, the last epidemic of St Louis
encephalitis was in Monroe, Louisiana, in 2001; 63 cases were reported, with 3 deaths (4.7% mortality). Infection with the La
Crosse encephalitis virus also usually occurs during the summer and early fall, with symptoms again being typical of acute
aseptic meningitis.[13]
Infections with the LCM virus occur worldwide. Most human cases occur among young adults during autumn.
Of fungal causes, B dermatitidis is reportedly endemic in North America (eg, Mississippi and Ohio River basins). It has also
been isolated from parts of Central America, South America, the Middle East, and India. H capsulatum has been reported
from many areas of the world, with the Mississippi and Ohio River valleys being the most endemic regions in North America.
Of parasitic causes, A cantonensis is common in Southeast Asia and the Pacific Islands. It has also been found in rats
outside this region, particularly in regions of Africa, Puerto Rico, and Louisiana, presumably introduced by ship-borne rats
from endemic areas. G spinigerum is common in Southeast Asia, China, and Japan but has been reported sporadically
worldwide.
Epidemiology of chronic meningitis
Brucella -associated chronic meningitis has a worldwide distribution and is common in the Middle East, India, Mexico, and
Central and South America. In the United States, after the control of bovine infections, the incidence decreased to less than
0.5 cases per 100,000 population, and only 79 cases were reported to the CDC in 1998.
M tuberculosis is worldwide in distribution, and humans are its only reservoir. In 1997, the estimated case rates among
endemic countries ranged from 62 to 411 cases per 100,000 population.
B burgdorferi is a tick-borne spirochete that is found in the temperate regions of much of the northern hemisphere. Endemic
regions include North America (eg, the northeastern United States, Minnesota, Wisconsin, and parts of California and
Oregon), Europe, and Asia.
C neoformans has a worldwide distribution. Serotypes B and C have been restricted mostly to tropical and subtropical
regions, and serotype B has been isolated from eucalyptus trees.
The distribution of C immitis is limited to the endemic regions of the Western Hemisphere, within the north and south 40°
latitudes (ie, parts of the southwestern United States, Mexico, and Central and South America). Persons who have migrated
from or traveled to endemic areas may experience onset of disease in other parts of the world.
S schenckii has been reported worldwide. However, most cases come from the tropical regions of the Americas.
Prognosis
Patients with bacterial meningitis who present with an impaired level of consciousness, hypotension, or seizures are at
increased risk for neurologic sequelae or death.[14]
In bacterial meningitis, several risk factors are associated with death and with neurologic disability. A risk score has been
derived and validated in adults with bacterial meningitis. This score includes the following variables, which are associated
with an adverse clinical outcome[15] :
Older age
Increased heart rate
Lower Glasgow Coma Scale score
CSF leukocyte count lower than 1000/μL
Gram-positive cocci on CSF Gram stain
Advanced bacterial meningitis can lead to brain damage, coma, and death. In 50% of patients, several complications may
develop in the days to weeks following infection. Long-term sequelae are seen in as many as 30% of survivors and vary with
etiologic agent, patient age, presenting features, and hospital course. Patients usually have subtle CNS changes.
Serious complications include the following:
Hearing loss
Cortical blindness
Other cranial nerve dysfunction
Paralysis
Muscular hypertonia
Ataxia
Multiple seizures
Mental motor retardation
Focal paralysis
Ataxia
Subdural effusions
Hydrocephalus
Cerebral atrophy
Risk factors for hearing loss after pneumococcal meningitis are female gender, older age, severe meningitis, and infection
with certain pneumococcal serotypes (eg, 12F).[16] Delayed complications include the following:
Decreased hearing or deafness

Delayed cerebral thrombosis [17]
Other cranial nerve dysfunctions
Multiple seizures
Focal paralysis
Subdural effusions
Hydrocephalus
Intellectual deficits
Ataxia
Blindness
Waterhouse-Friderichsen syndrome
Peripheral gangrene
Seizures are a common and important complication, occurring in approximately one fifth of patients. The incidence is higher
in patients younger than 1 year, reaching 40%. Approximately one half of patients with this complication have repeated
seizures. Patients may die as a result of diffuse CNS ischemic injury or systemic complications.
Even with effective antimicrobial therapy, significant neurologic complications have been reported to occur in as many as
30% of survivors of bacterial meningitis. Close monitoring for the development of these complications is essential.
Mortality for bacterial meningitis is highest in the first year of life, decreases in midlife, and increases again in old age.
Bacterial meningitis is fatal in 1 in 10 cases, and 1 of every 7 survivors is left with a severe handicap, such as deafness or
brain injury.
The prognosis in patients with meningitis caused by opportunistic pathogens depends on the underlying immune function of
the host. Many patients who survive the disease require lifelong suppressive therapy (eg, long-term fluconazole for
suppression in patients with HIV-associated cryptococcal meningitis).
Among bacterial pathogens, S pneumoniae causes the highest mortality (20-30% in adults, 10% in children) and morbidity
(15%) in meningitis. If severe neurologic impairment is evident at the time of presentation (or if the onset of illness is
extremely rapid), mortality is 50-90% and morbidity is even higher, even with immediate medical treatment. Meningitis
caused by L monocytogenes or gram-negative bacilli also has a higher case-fatality rate than meningitis caused by other
bacterial agents.
Reported overall mortality for meningitis from specific bacterial organisms is as follows:
S pneumoniae - 19-26%
H influenzae - 3-6%
N meningitidis - 3-13%
L monocytogenes - 15-29%
Patients with meningococcal meningitis have a better prognosis than do those with pneumococcal meningitis, with a
mortality of 4-5%; however, patients with meningococcemia have a poor prognosis, with a mortality of 20-30%.
The mortality for viral meningitis without encephalitis is less than 1%. In patients with deficient humoral immunity (eg,
agammaglobulinemia), enteroviral meningitis may have a fatal outcome. Patients with viral meningitis usually have a good
prognosis for recovery. The prognosis is worse for patients at the extremes of age (ie, < 2 or >60 years) and those with
significant comorbidities and underlying immunodeficiency.
Patient Education
Patients and parents of young children should be educated about the benefits of vaccination in preventing meningitis.
Vaccination against N meningitidis is recommended for all US college students.
Close contacts of patients with known or suspected N meningitidis or Hib meningitis may require education regarding the
need for prophylaxis. All contacts should be instructed to come to the emergency department immediately at the first sign of
fever, sore throat, rash, or symptoms of meningitis. Rifampin prophylaxis only eradicates the organism from the
nasopharynx; it is ineffective against invasive disease.
For patient education information, see the Brain and Nervous System Center and the Children’s Health Center, as well as
Meningitis in Adults, Meningitis in Children, Brain Infection, and Spinal Tap.
Presentation
History
Only about 44% of adults with bacterial meningitis exhibit the classic triad of fever, headache, and neck stiffness.[18] These
symptoms can develop over several hours or over 1-2 days. In a large prospective study of 696 cases of adults with bacterial
meningitis, van de Beek et al reported that 95% of the patients had 2 out of the following 4 symptoms: fever, headache, stiff
neck, and altered mental status.[18]
Other symptoms can include the following:
Nausea
Vomiting
Photalgia (photophobia) - Discomfort when the patient looks into bright lights
Sleepiness
Confusion
Irritability
Delirium
Coma
Approximately 25% of patients with bacterial meningitis present acutely, well within 24 hours of the onset of symptoms.
Occasionally, if a patient has been taking antibiotics for another infection, meningitis symptoms may take longer to develop
or may be less intense.
Approximately 25% of patients have concomitant sinusitis or otitis that could predispose to S pneumoniae meningitis.[18] In
contrast, patients with subacute bacterial meningitis and most patients with viral meningitis present with neurologic
symptoms developing over 1-7 days. Chronic symptoms lasting longer than 1 week suggest the presence of meningitis
caused by certain viruses or by tuberculosis, syphilis, fungi (especially cryptococci), or carcinomatosis.
Patients with viral meningitis may have a history of preceding systemic symptoms (eg, myalgias, fatigue, or anorexia).
Patients with meningitis caused by the mumps virus usually present with the triad of fever, vomiting, and headache. This
follows the onset of parotitis (salivary gland enlargement occurs in 50% of patients), which clinically resolves in 7-10 days.
As bacterial meningitis progresses, patients of any age may have seizures (30% of adults and children; 40% of newborns
and infants). In patients who have previously been treated with oral antibiotics, seizures may be the sole presenting
symptom; fever and changes in level of alertness or mental status are less common in partially treated meningitis than in
untreated meningitis.
Atypical presentation may be observed in certain groups. Elderly individuals, especially those with underlying comorbidities
(eg, diabetes, renal and liver disease), may present with lethargy and an absence of meningeal symptoms. Patients with
neutropenia may present with subtle symptoms of meningeal irritation.
Other immunocompromised hosts, including organ and tissue transplant recipients and patients with HIV and AIDS, may
also have an atypical presentation. Immunosuppressed patients may not show dramatic signs of fever or meningeal
inflammation.
A less dramatic presentation―headache, nausea, minimal fever, and malaise―may be found in patients with low-grade
ventriculitis associated with a ventriculoperitoneal shunt. Newborns and small infants also may not present with the classic
symptoms, or the symptoms may be difficult to detect. An infant may appear only to be slow or inactive, or be irritable,
vomiting, or feeding poorly. Other symptoms in this age group include temperature instability, high-pitched crying, respiratory
distress, and bulging fontanelles (a late sign in one third of neonates).
Epidemiologic factors and predisposing risks should be assessed in detail. These may suggest the specific etiologic agent.
Exposures
A history of exposure to a patient with a similar illness is an important diagnostic clue. It may point to the presence of
epidemic disease, such as viral or meningococcal meningitis.
Elicit any history of sexual contact or high-risk behavior from the patient. Herpes simplex virus (HSV) meningitis is
associated with primary genital HSV infection and HIV infection. A history of recurrent bouts of benign aseptic meningitis
suggests Mollaret syndrome, which is caused by HSV.
Animal contacts should be elicited. Patients with rabies could present atypically with aseptic meningitis; rabies should be
suspected in a patient with a history of animal bite (eg, from a skunk, raccoon, dog, fox, or bat). Exposure to rodents
suggests infection with lymphocytic choriomeningitis virus (LCM) virus and Leptospira infection. Laboratory workers dealing
with these animals also are at increased risk of contracting LCM.
Brucellosis may be transmitted through contact with infected farm animals (eg, cows or pigs). The intake of unpasteurized
milk and cheese also predisposes to brucellosis, as well as to L monocytogenes infection.
Previous medical treatment and existing conditions
A history of recent antibiotic use should be elicited. As many as 40% of patients who present with acute or subacute
bacterial meningitis have previously been treated with oral antibiotics (presumably because of misdiagnosis at the time of
initial presentation).
The presence of a ventriculoperitoneal shunt or a history of recent cranial surgery should be elicited. Patients with low-grade
ventriculitis associated with a ventriculoperitoneal shunt may have a less dramatic presentation than those with acute
bacterial meningitis, experiencing headache, nausea, minimal fever, and malaise. The presence of cochlear implants with a
positioner has been associated with a higher risk of bacterial meningitis.
Alcoholism and cirrhosis are risk factors for meningitis. Unfortunately, the multiple etiologies of fever and seizures in patients
with alcoholism or cirrhosis make meningitis challenging to diagnose.
Location and travel
Geographic location and travel history are important in the evaluation of patients. Infection with H capsulatum or B
dermatitidis is considered in patients with exposure to endemic areas of the Mississippi and Ohio River valleys; C immitis is
considered in regions of the southwestern United States, Mexico, and Central America. B burgdorferi is considered in
regions of the northeastern and northern central United States, if tick exposure is a possibility.
Season and temperature
The time of year is an important variable because many infections are seasonal. With enteroviruses (which are found
worldwide), infections occur during late summer and early fall in temperate climates and year-round in tropical regions. In
contrast, mumps, measles, and varicella-zoster virus (VZV) are more common during winter and spring. Arthropod-borne
viruses (eg, West Nile virus, St Louis encephalitis, and California encephalitis virus) are more common during the warmer
months.
Physical Examination
The classic triad of meningitis consists of fever, nuchal rigidity, and altered mental status, but not all patients have all 3, and
almost all patients have headache. Altered mental status can range from irritability to somnolence, delirium, and coma. The
examination reveals no focal neurologic deficits in the majority of cases. Furthermore, the majority of patients with bacterial
meningitis have a stiff neck, but the meningeal signs are insensitive for diagnosis of meningitis.[19]
Acute bacterial meningitis in otherwise healthy patients who are not at the extremes of age presents in a clinically obvious
fashion. In contrast, most patients with subacute bacterial meningitis pose a diagnostic challenge. Systemic examination
occasionally reveals a pulmonary or otitis media coinfection.
Systemic findings can also be present. Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia, or urinary
tract infection [UTI]) may be noted. Endotoxic shock with vascular collapse is characteristic of severe N meningitidis
(meningococcal) infection.
General physical findings in viral meningitis are common to all causative agents, but some viruses produce unique clinical
manifestations that help focus the diagnostic approach. Enteroviral infection is suggested by the presence of the following:
Exanthemas
Symptoms of pericarditis, myocarditis, or conjunctivitis
Syndromes of pleurodynia, herpangina, and hand-foot-and-mouth disease
Increased blood pressure with bradycardia can also be present. Vomiting occurs in 35% of patients.
Nonblanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N meningitidis (50%), H
influenzae, S pneumoniae, or S aureus.[20] Arthritis is seen with meningococcal infection and with M pneumoniae infection
but is less common with other bacterial species.
Infants
Infants may have the following:
Bulging fontanelle (if euvolemic)
Paradoxic irritability (ie, remaining quiet when stationary and crying when held)
High-pitched cry
Hypotonia
In infants, the clinicians should examine the skin over the entire spine for dimples, sinuses, nevi, or tufts of hair. These may
indicate a congenital anomaly communicating with the subarachnoid space.
Focal neurologic signs
Focal neurologic signs include isolated cranial nerve abnormalities (principally of cranial nerves III, IV, VI, and VII), which are
present in 10-20% of patients. These result from increased intracranial pressure (ICP) or the presence of exudates encasing
the nerve roots. Focal cerebral signs are present in 10-20% of patients and may develop as a result of ischemia from
vascular inflammation and thrombosis.
Papilledema is a rare finding (< 1% of patients) that also indicates increased ICP, but it is neither sensitive nor specific: it
occurs in only one third of meningitis patients with increased ICP and is present not only in meningitis but also in brain
abscess and other disorders.
Signs of meningeal irritation
For more than 100 years, clinicians have relied on meningeal signs (nuchal rigidity, Kernig sign, and Brudzinski sign) to
evaluate patients with suspected meningitis and help determine who should undergo a lumbar puncture (LP). However, a
prospective study of 297 adults with suspected meningitis documented very low sensitivities for these signs: 5% for the
Kernig sign, 5% for the Brudzinski sign, and 30% for nuchal rigidity.[19] Thus, the absence of the meningeal signs should not
defer the performance of the LP.
Systemic and extracranial findings
Systemic findings on physical examination may provide clues to the etiology of a patient’s meningitis. Morbilliform rash with
pharyngitis and adenopathy may suggest a viral etiology (eg, Epstein-Barr virus [EBV], cytomegalovirus [CMV], adenovirus,
or HIV). Macules and petechiae that rapidly evolve into purpura suggest meningococcemia (with or without meningitis).
Vesicular lesions in a dermatomal distribution suggest VZV. Genital vesicles suggest HSV-2 meningitis.
Sinusitis or otitis suggests direct extension into the meninges, usually with S pneumoniae or, less often, H influenzae.
Rhinorrhea or otorrhea suggests a cerebrospinal fluid (CSF) leak from a basilar skull fracture, with meningitis most
commonly caused by S pneumoniae.
Hepatosplenomegaly and lymphadenopathy suggest a systemic disease, including viral (eg, mononucleosislike syndrome in
EBV, CMV, and HIV) and fungal (eg, disseminated histoplasmosis). The presence of a heart murmur suggests infective
endocarditis with secondary bacterial seeding of the meninges.
Chronic meningitis
It is essential to perform careful general, systemic, and neurologic examinations, looking especially for the following:
Lymphadenopathy
Papilledema and tuberculomas during funduscopy
Meningismus
The presentation of chronic tuberculous meningitis may be acute, but the classic presentation is subacute and spans weeks.
Patients generally have a prodrome consisting of fever of varying degrees, malaise, and intermittent headaches. Cranial
nerve palsies (III, IV, V, VI, and VII) often develop, suggesting basilar meningeal involvement.
Clinical staging of tuberculous meningitis is based on neurologic status, as follows:
Stage 1 - No change in mental function, with no deficits and no hydrocephalus
Stage 2 - Confusion and evidence of neurologic deficit
Stage 3 - Stupor and lethargy
Syphilitic meningitis
The median incubation period before the appearance of symptoms in chronic syphilitic meningitis is 21 days (range, 3-90
days), during which time spirochetemia develops. Syphilitic meningitis usually occurs during the primary or secondary stage
of syphilis, complicating 0.3-2.4% of primary infections during the first 2 years. Its presentation is similar to those of other
types of aseptic meningitis, including headache, nausea, vomiting, and meningismus.
Meningovascular syphilis occurs later in the course of untreated syphilis, and the symptoms are dominated by focal syphilitic
arteritis (ie, focal neurologic symptoms associated with signs of meningeal irritation) that spans weeks to months and results
in stroke and irreversible damage if left untreated. Patients with concomitant HIV infection have an increased risk of
accelerated progression.
Lyme meningitis
Although rare during stage 1 of Lyme disease, central nervous system (CNS) involvement with meningitis may occur in Lyme
disease–associated chronic meningitis and is characterized by the concurrent appearance of erythema migrans at the site of
the tick bite. More commonly, aseptic meningitis syndrome occurs 2-10 weeks after the erythema migrans rash. This
represents stage 2 of Lyme disease, or the borrelial hematogenous dissemination stage.
Headache is the most common symptom of Lyme disease–associated chronic meningitis, with photophobia, nausea, and
neck stiffness occurring less frequently. Somnolence, emotional lability, and impaired memory and concentration may occur.
Facial nerve palsy is the most common cranial nerve deficit. These symptoms of meningitis usually fluctuate and may last for
months if left untreated.
Fungal meningitis
Meningitis from C neoformans usually develops in patients with defective cell-mediated immunity (see CNS Cryptococcosis
in HIV). It is characterized by the gradual onset of symptoms, the most common of which is headache.
Coccidioidal meningitis is the most serious form of disseminated coccidioidomycosis; it usually is fatal if left untreated. These
patients may present with headache, vomiting, and altered mental function associated with pleocytosis, elevated protein
levels, and decreased glucose levels. Eosinophils may be a prominent finding on CSF analysis.
Patients infected with B dermatitidis may present with an abscess or fulminant meningitis. Patients infected with H
capsulatum may present with headache, cranial nerve deficits, or changes in mental status months before diagnosis.
Helminthic eosinophilic meningitis
After ingestion of A cantonensis larvae, which are found in raw or undercooked mollusks, most patients with symptomatic
disease present with nonspecific and self-limited abdominal pain caused by larval migration into the bowel wall. On rare
occasions, the larvae can migrate into the CNS and cause eosinophilic meningitis. Although A cantonensis is prevalent in
Southeast Asia and tropical Pacific islands, infestations from this parasitic nematode have been reported in the United
States and the Caribbean.[21]
Aseptic meningitis
In contrast to patients with bacterial meningitis, patients with aseptic meningitis syndrome usually appear clinically nontoxic,
with no vascular instability. (See Aseptic Meningitis.) In many cases, a cause for meningitis is not apparent after initial
evaluation, and the condition is therefore classified as aseptic meningitis. These patients characteristically have an acute
onset of meningeal symptoms, fever, and CSF pleocytosis that is usually prominently lymphocytic.
Complications
Immediate complications of meningitis include the following:
Septic shock, including disseminated intravascular coagulation (DIC)
Coma with loss of protective airway reflexes
Seizures, which occur in 30-40% of children and 20-30% of adults
Cerebral edema
Septic arthritis
Pericardial effusion
Hemolytic anemia (H influenzae)
Delayed complications include the following:
Decreased hearing or deafness
Other cranial nerve dysfunctions
Multiple seizures
Focal paralysis
Subdural effusions
Hydrocephalus
Intellectual deficits
Ataxia
Blindness
Waterhouse-Friderichsen syndrome
Peripheral gangrene
Cerebral edema, cranial nerve palsy, and cerebral infarction

Some degree of cerebral edema is common with bacterial meningitis. This complication is an important cause of death.
Cranial nerve palsies and the effects of impaired cerebral blood flow, such as cerebral infarction, are caused by increased
ICP. In certain cases, repeated LP or the insertion of a ventricular drain may be necessary to relieve the effects of this
increase.
In cerebral infarction, endothelial cells swell, proliferate, and crowd into the lumen of the blood vessel, and inflammatory cells
infiltrate the blood vessel wall. Foci of necrosis develop in the arterial and venous walls and induce arterial and venous
thrombosis. Venous thrombosis is more frequent than arterial thrombosis, but arterial and venous cerebral infarctions can be
seen in 30% of patients.
Brain parenchymal damage
Brain parenchymal damage is the most important and feared complication of bacterial meningitis. It can lead to the following
disorders:
Sensory and motor deficits
Cerebral palsy
Learning disabilities
Mental retardation
Cortical blindness
Seizures
Cerebritis
Inflammation often extends along the perivascular (Virchow-Robin) spaces into the underlying brain parenchyma.
Commonly, cerebritis results from direct spread of infection, either from otorhinologic infection or meningitis (including
retrograde septic thrombophlebitis) or from hematogenous spread from an extracranial focus of infection. Parenchymal
involvement, with edema and mass effect, may be localized or diffuse. Cerebritis can evolve to frank abscess formation in
the gray matter–white matter junction.
Subdural effusion
In children with meningitis who are younger than 1 year, 20-50% of cases are complicated by sterile subdural effusions. Most
of these effusions are transient and small to moderate in size. About 2% of them are infected secondarily and become
subdural empyemas. In the empyema, infection and necrosis of the arachnoid membrane permit formation of a subdural
collection.
In addition to young age, risk factors include rapid onset of illness, low peripheral white blood cell (WBC) count, and high
CSF protein level. Seizures occur more commonly during the acute course of the disease, though long-term sequelae of
promptly treated subdural effusions are similar to those of uncomplicated meningitis.
Ventriculitis
Ventriculitis may occur through the involvement of the ependymal lining of the ventricles. This complication occurs in 30% of
patients overall but is especially common in neonates, with an incidence as high as 92%. The organisms enter the ventricles
via the choroid plexuses. As a result of reduced CSF flow, and possibly of reduced secretion of CSF by the choroid plexus,
the infective organisms remain in the ventricles and multiply.
Ventriculomegaly
Ventriculomegaly can occur early or late in the course of meningitis and is usually transient and mild to moderate in severity.
As a result of the subarachnoid inflammatory exudate, CSF pathways may become obstructed, leading to hydrocephalus.
Exudates in the foramina of Luschka and Magendie can cause noncommunicating hydrocephalus, whereas exudates that
accumulate in the basilar cisterns or over the cerebral convexity can develop into communicating hydrocephalus.
DDx
Diagnostic Considerations
Diagnoses to consider aside from meningitis include the following:
Noninfectious meningitis, including medication-induced meningeal inflammation
Meningeal carcinomatosis
Central nervous system (CNS) vasculitis
Stroke
Encephalitis
All causes of altered mental status and coma
Leptospirosis
Subdural empyema
Differential Diagnoses
Brain Abscess
Brain Neoplasms
Delirium Tremens (DTs)
Emergent Management of Subarachnoid Hemorrhage
Encephalitis
Febrile Seizures
Herpes Simplex Encephalitis
Herpes Simplex Virus (HSV) in Emergency Medicine
Pediatrics, Meningitis and Encephalitis
Workup
Workup
Approach Considerations
The diagnostic challenges in patients with clinical findings of meningitis are as follows:
Early identification and treatment of patients with acute bacterial meningitis
Assessing whether a treatable central nervous system (CNS) infection is present in those with suspected subacute or
chronic meningitis
Identifying the causative organism
Bacterial meningitis must be the first and foremost consideration in the differential diagnosis of patients with headache, neck
stiffness, fever, and altered mental status. Acute bacterial meningitis is a medical emergency, and delays in instituting
effective antimicrobial therapy result in increased morbidity and mortality.
In general, whenever the diagnosis of meningitis is strongly considered, a lumbar puncture should be promptly performed.
Examination of the cerebrospinal fluid (CSF) is the cornerstone of the diagnosis. The diagnosis of bacterial meningitis is
made by culture of the CSF sample. The opening pressure should be measured and the fluid sent for cell count (and
differential count), chemistry (ie, CSF glucose and protein), and microbiology (ie, Gram stain and cultures).
A concern regarding LP is that the lowering of CSF pressure from withdrawal of CSF could precipitate herniation of the brain.
Herniation can sometimes occur in acute bacterial meningitis and other CNS infections as the consequence of severe
cerebral edema or acute hydrocephalus. Clinically, this is manifested by an altered state of consciousness, abnormalities in
pupil reflexes, and decerebrate or decorticate posturing. The incidence of herniation after LP, even in patients with
papilledema, is approximately 1%.
A screening computed tomography (CT) scan of the head may be performed before LP to determine the risk of herniation. A
prospective study involving 301 adults with suspected meningitis found that the following baseline patient characteristics
were associated with an abnormal finding on head CT[22] :
Age ≥60 years
Immunocompromise (ie, HIV infection/AIDS, immunosuppressive therapy, or transplantation)
A history of CNS disease
A history of seizure within 1 week before presentation
Any abnormality on neurologic examination
These factors have been included in the Infectious Diseases Society of America guidelines to decide who should undergo
CT before LP.[23]
Obtaining a CT scan in a patient without any of the IDSA guidelines indications is of no clinical benefit and should be
avoided.[24]
The decision to obtain a brain CT scan before LP should not delay the institution of antibiotic therapy; such delay can
increase mortality. It should be also noted that herniation can occur in patients with bacterial meningitis who have a normal
brain CT scan. The most reliable clinical signs that indicate the risk of herniation include deteriorating level of consciousness,
brainstem signs, and a very recent seizure.
Other laboratory tests, which may include blood cultures, are needed to complement the CSF culture. These bacterial
cultures are used for identification of the offending bacteria and occasionally its serogroup, as well as for determination of
the organism’s susceptibility to antibiotics. Special studies, such as serology and nucleic acid amplification, may also be
performed, depending on clinical suspicion of an offending organism.
As many as 50% of patients with pneumococcal meningitis also have evidence of pneumonia on initial chest radiography.
This association occurs in fewer than 10% of patients with meningitis caused by H influenzae or N meningitidis and in
approximately 20% of patients with meningitis caused by other organisms. (See Imaging in Bacterial Meningitis.)
Blood Studies
In patients with bacterial meningitis, a complete blood count (CBC) with differential will demonstrate polymorphonuclear
leukocytosis with a left shift. Useful elements of the metabolic panel include the following:
Serum electrolytes, to determine dehydration or syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
Serum glucose (which is compared with the CSF glucose)
Blood urea nitrogen (BUN) or creatinine and liver profile, to assess organ function and adjust antibiotic dosing
HIV testing
The serum glucose level may be low if glycogen stores are depleted, or they may be high in infected patients with diabetes.
A coagulation profile and platelet count are indicated in cases of chronic alcohol use, chronic liver disease, or suspected
disseminated intravascular coagulation (DIC). Patients with coagulopathies may require platelets or fresh frozen plasma
(FFP) before LP.
Cultures and Bacterial Antigen Testing

Obtaining cultures before instituting antibiotics may be helpful if the diagnosis is uncertain. The utility of cultures is most
evident when LP is delayed until head imaging can rule out the risk of brain herniation, in which cases adjunctive
dexamethasone and antimicrobial therapy is rightfully initiated before CSF samples can be obtained. These cultures include
the following:
Blood - 50% positive in meningitis caused by H influenzae, S pneumoniae, or N meningitidis
Nasopharynx
Respiratory secretions
Urine
Skin lesions
Latex agglutination or counterimmunoelectrophoresis (CIE) of blood, urine, and CSF for specific bacterial antigens is
occasionally recommended if diagnosis is challenging or in patients with partially treated meningitis. The Binax NOW S
pneumoniae antigen test, if done on CSF, has a 99%-100% sensitivity and specificity and can even be positive despite prior
antibiotic therapy.[25]
The use of nucleic acid amplification (eg, polymerase chain reaction [PCR] testing) has revolutionized the diagnosis of
herpes simplex virus (HSV) meningitis. The availability of this technique has confirmed HSV as the cause of the recurrent
Mollaret meningitis. This technique has also been applied to the diagnosis of enteroviral infections and the other herpesvirus
infections. The PCR assay for enteroviruses has been demonstrated to be substantially more sensitive than culture and is
94-100% specific.
A multiplex PCR panel that identifies 14 pathogens (E coli K1, H influenzae, L monocytogenes, N meningitidis, S agalactiae,
S pneumoniae, cytomegalovirus, enterovirus, herpes simplex virus 1, herpes simplex virus 2, human herpes virus 6, human
parechovirus, varicella zoster, C neoformans/Cryptococcus gattii) in 1 hour with 0.2 mL of CSF is now widely available.
Syphilis Testing
Perform serologic tests to detect syphilis. Screening for syphilis is done with the nontreponemal tests: rapid plasma reagent
(RPR) or Venereal Disease Research Laboratory (VDRL). Positive results are confirmed with one of the following specific
treponemal tests:
Fluorescent treponemal antibody absorption (FTA-Abs)
T pallidum hemagglutination (TPHA)
Microhemagglutination– T pallidum (MHA-TP)
The newer immune-capture enzyme immunoassay (ICE Syphilis) recombinant antigen test
In patients with syphilis, initial results on nontreponemal tests can serve as a baseline for gauging the success of therapy.
Titers decrease and usually revert to negative or undetectable levels following effective treatment.
Serum Procalcitonin Testing

Increasing data suggest that serum procalcitonin (PCT) levels can be used as a guide to distinguish between bacterial and
aseptic meningitis in children. Elevated serum PCT levels predict bacterial meningitis. The results of serum PCT testing,
combined with other findings, could be helpful in making clinical decisions.[26]
In an analysis of retrospective, multicenter, hospital-based cohort studies, Dubos et al confirmed that measurement of the
PCT level is the best biologic marker for differentiating bacterial meningitis from aseptic meningitis in children in the
emergency department (ED). With a threshold of 0.5 ng/mL, the sensitivity and specificity of the PCT level in distinguishing
between bacterial and aseptic meningitis were 99% and 83%, respectively.[26]
Lumbar Puncture and CSF Analysis

Elevated opening pressure correlates with increased risk of morbidity and mortality in bacterial and fungal meningitis. In
bacterial meningitis, elevated opening pressure (reference range, 80-200 mm H2 O) suggests increased intracranial
pressure (ICP) from cerebral edema. In viral meningitis, the opening pressure is usually within the reference range. The CSF
opening pressure may be elevated at times in cryptococcal meningitis, suggesting increased ICP, and it is usually elevated in
tuberculous meningitis.
The CSF cell count varies according to the offending pathogen (see Tables 5 and 6 below). It is usually in the few hundreds
(100-1000/µL) with a predominance of lymphocytes in patients with viral meningitis. Some cases of echovirus, mumps, and
HSV meningitis may produce a neutrophilic picture early in the course of disease. (See Lumbar Puncture.)
Table 5. CSF Findings in Meningitis by Etiologic Agent (Open Table in a new window)
Opening
WBC count Glucose Protein
Agent Pressure Microbiology
(cells/µL) (mg/dL) (mg/dL)
(mm H2 O)
100-5000; Specific pathogen

Bacterial
200-300 >80% < 40 >100 demonstrated in 60% of Gram
meningitis
PMNs stains and 80% of cultures
Normal, Normal but

Viral 10-300; reduced in may be
90-200 Viral isolation, PCR assays
meningitis lymphocytes LCM and slightly
mumps elevated
Tuberculous 100-500; Reduced, < Elevated, Acid-fast bacillus stain, culture,

180-300
meningitis lymphocytes 40 >100 PCR
Cryptococcal 10-200; India ink, cryptococcal antigen,

180-300 Reduced 50-200
meningitis lymphocytes culture
Normal but
Aseptic 10-300; may be
90-200 Normal Negative findings on workup
meningitis lymphocytes slightly
elevated
Normal 0-5;
80-200 50-75 15-40 Negative findings on workup
values lymphocytes
LCM = lymphocytic choriomeningitis; PCR = polymerase chain reaction; PMN = polymorphonuclear leukocyte; WBC =
white blood cell.
Table 6. Comparison of CSF Findings by Type of Organism (Open Table in a new window)
Normal Finding Bacterial Meningitis Viral Meningitis* Fungal Meningitis**
Pressure (mm Increased Normal or mildly Normal or mildly

H2 O) increased increased in
tuberculous
50-150 meningitis; may be
increased in fungal;
AIDS patients with
cryptococcal
meningitis have
increased risk of
blindness and death
unless kept below
300 mm H2 O
Cell count usually < 500,

No cell count result can exclude bacterial
nearly 100%
meningitis; PMN count typically in 1000s but
mononuclear; up to 48
may be less dramatic or even normal
Cell count hours, significant PMN
(classically, in very early meningococcal
(mononuclear pleocytosis may be
meningitis and in extremely ill neonates);
cells/µL) indistinguishable from
lymphocytosis with normal CSF chemistries
early bacterial meningitis;
seen in 15-25%, especially when cell counts Hundreds of
Preterm: 0-25 this is particularly true
< 1000 or with partial treatment; ~90% of mononuclear cells
with eastern equine
patients with ventriculoperitoneal shunts
Term: 0-22 encephalitis; presence of
who have CSF WBC count >100 are
nontraumatic RBCs in
>6 months: 0-5 infected; CSF glucose is usually normal,
80% of HSV
and organisms are less pathogenic; cell
meningoencephalitis,
count and chemistries normalize slowly
though 10% have normal
(over days) with antibiotics
CSF results
India ink is 50%

sensitive for fungi;
Gram stain 80% sensitive; inadequate cryptococcal antigen
decolorization may mistake Haemophilus is 95% sensitive;
Microscopy influenzae for gram-positive cocci; AFB stain is 40%
pretreatment with antibiotics may affect No organism sensitive for
No organisms stain uptake, causing gram-positive tuberculosis
organisms to appear gram-negative and (increase yield by
decrease culture yield by average of 20% staining supernatant
from at least 5 mL
CSF)
Sometimes
Glucose decreased; aside
from fulminant
Euglycemia: bacterial meningitis,
>50% serum lowest levels of CSF
glucose are seen in
Decreased Normal
Hyperglycemia: tuberculous
>30% serum meningitis, primary
amebic
Wait 4 hr after meningoencephalitis,
glucose load and
neurocysticercosis
Protein (mg/dL)
Preterm: 65- Increased; >1000

150 with relatively benign
Usually >150, may be >1000 Mildly increased clinical presentation
Term: 20-170 suggestive of fungal
disease
>6 months: 15-
45
AFB = acid-fast bacillus; CSF = cerebrospinal fluid; HSV = herpes simplex virus; RBC = red blood cell; PMN =
polymorphonuclear leukocyte.
*Some bacteria (eg, Mycoplasma, Listeria, Leptospira spp, Borrelia burgdorferi [Lyme], and spirochetes) produce spinal
fluid alterations that resemble the viral profile. An aseptic profile also is typical of partially treated bacterial infections
(>33% of patients have received antimicrobial treatment, especially children) and the 2 most common causes of
encephalitis—the potentially curable HSV and arboviruses.
**In contrast, tuberculous meningitis and parasites resemble the fungal profile more closely.
CFS sample handling
After drawing the CSF sample, do the following with the tubes:
Tube 1 – Send to the chemistry laboratory for glucose and protein
Tube 2 – Send to the hematology laboratory for a cell count with differential
Tube 3 – Send to the microbiology and immunology laboratory
Tube 4 – Hold for a repeat cell count with differential, if needed (or for other subsequent studies not initially ordered)
Microbiology and immunology studies for tube 3 include the following:
Gram stain
Bacterial culture
Acid-fast bacillus (AFB) stain and tuberculosis cultures
India ink stain
Cryptococcal antigen testing
Fungal cultures, counterimmunoelectrophoresis (CIE), VDRL, and cryptococcal antigen, if indicated
Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, and other cytokines have received increasing attention as mediators
of the inflammatory response during bacterial meningitis. Leist et al reported detecting TNF-α in the CSF of 3 of 3 patients
with bacterial meningitis, but in 0 of 7 patients with viral meningitis. Lopez-Cortez et al demonstrated that a TNF-α level
higher than 150 pg/mL and an IL-1β level higher than 90 pg/mL showed sensitivities of 74% and 90%, respectively, in
discriminating viral from aseptic meningitis.
Mustafa et al demonstrated that IL-1β can be detected in the CSF of 95% of infants and children with bacterial meningitis
and that levels higher than 500 pg/mL were correlated with an increased risk of neurologic sequelae.[27]
These findings, though requiring both confirmation and amplification, suggest that analysis of TNF and other cytokines, in
particular IL-1β, may prove valuable in differentiating acute bacterial meningitis from viral meningitis and possibly in
detecting patients at particular risk for an adverse outcome. Their role in guiding adjunctive therapy, such as corticosteroids
and nonsteroidal treatment of blood-brain barrier injury, is also under investigation.
CSF characteristics of acute bacterial meningitis
Examination of the CSF in patients with acute bacterial meningitis reveals the characteristic neutrophilic pleocytosis (cell
count usually ranging from hundreds to a few thousand, with >80% PMNs). In some (25-30%) cases of L monocytogenes
meningitis, a lymphocytic predominance may occur. A low CSF white blood cell (WBC) count (< 20/µL) in the presence of a
high bacterial load suggests a poor prognosis.
According to Seupaul, the following 3 findings on CSF analysis have clinically useful likelihood ratios for the diagnosis of
bacterial meningitis in adults[28] :
CSF glucose−to−blood glucose ratio of 0.4 or lower
CSF WBC count of 500/µL or higher
CSF lactate level of 31.53 mg/dL or higher
CSF characteristics of viral meningitis
In viral meningitis, the opening pressure is 90-200 mm H2 O, and the WBC count is 10-300/µL. Although the glucose
concentration is typically normal, it can be below normal in meningitis from lymphocytic choriomeningitis virus (LCM), herpes
simplex virus (HSV), mumps virus, and poliovirus. The protein concentration tends to be slightly elevated, but it can be within
the reference range.
CSF characteristics of fungal meningitis
The diagnosis of cryptococcal meningitis relies on the identification of the pathogen in the CSF. The CSF is characterized by
a lymphocytic pleocytosis (10-200/µL), a reduced glucose level, and an elevated protein level. The CSF picture of other
fungal meningitides is similar to that of cryptococcal meningitis, usually with lymphocytic pleocytosis. Eosinophilic pleocytosis
has rarely been associated with C immitis meningitis.
The definitive diagnosis usually relies on the demonstration of the specific fungal agent (eg, H capsulatum, C immitis, B
dermatitidis, or Candida species) from clinical specimens, including the CSF. This could be in the form of fungal culture
isolation (eg, C albicans growth from CSF).
More commonly, fungal serology (eg, presence of histoplasma antigen in the CSF) is used in the diagnosis of many cases of
fungal meningitis because isolating these organisms from culture has proved difficult. It should be noted, however, that the
serology for B dermatitidis is not accurate and a negative serology finding does not rule out the diagnosis.
A test used to detect fungal infection in the blood was successfully used in the diagnosis of fungal meningitis in an outbreak
caused by contaminated steroids.[29] This outbreak involved 13,534 US patients who underwent epidural steroid injection
and were exposed to methylprednisolone acetate from lots contaminated with environmental fungi; hundreds of these
individuals developed serious CNS complications. The test (Fungitell, Beacon Diagnostics Laboratories), which measures
levels of b-D-glucan (a glycoprotein found in the fungal cell wall), was used in CSF samples from patients exposed to the
contaminated steroids who had negative fungal culture and polymerase chain reaction results. All patients with fungal
meningitis had detectable b-D-glucan in their CSF.[29]
CSF characteristics of eosinophilic/parasitic meningitis
Primary amebic meningoencephalitis (PAM) caused by N fowleri is characterized by a neutrophilic pleocytosis, low glucose
levels, elevated protein levels, and red blood cells (RBCs). Mononuclear pleocytosis may be observed in patients with
subacute or chronic forms of PAM. Demonstration of the trophozoites, with the characteristic ameboid movement, on wet
preparations of the CSF has been used for diagnosis. Alternatively, the ameba may be demonstrated in biopsy specimens.
In the presence of exposure, profound peripheral blood eosinophilia, and characteristic eosinophilic pleocytosis, suspicion of
meningitis caused by A cantonensis, G spinigerum, or B procyonis should be entertained. Demonstrating the larvae ante
mortem is usually difficult, and diagnosis relies on clinical presentation and a compatible epidemiologic history. Serologic
tests may aid in the diagnosis. G spinigerum meningitis may mimic cerebrovascular disease in that it may cause cerebral
hemorrhage.
CSF characteristics of Lyme meningitis
In patients with Lyme meningitis, the CSF is characterized by low-grade lymphocytic pleocytosis, low glucose levels, and
elevated protein levels. Oligoclonal bands reactive to B burgdorferi antigens may be present. Demonstration of the specific
antibody to B burgdorferi aids in the diagnosis.
Comparison between the antibody response in the CSF and that in the serum is a helpful diagnostic test. A CSF-to-serum
ratio greater than 1 suggests intrathecal antibody production and neuroborreliosis.
CSF characteristics of tuberculous meningitis
In patients with tuberculous meningitis, the CSF is characterized by a predominantly lymphocytic pleocytosis; an elevated
protein level, especially if a CSF block is present; and a low glucose level (< 40 mg/dL). PCR testing can provide a rapid
diagnosis, though false-negative results may occur in samples containing very few organisms (< 2 colony-forming units
[cfu]/mL). (See Tuberculous Meningitis.)
CSF glucose and protein
In bacterial meningitis, the CSF glucose level (reference range, 40-70 mg/dL) is less than 40 mg/dL in 60% of patients. A
simultaneous blood glucose determination should be obtained for the purposes of comparison. In patients with elevated
blood glucose levels as a result of diabetes mellitus, the CSF-to-blood glucose ratio may not be predictive. The CSF glucose
level is usually within the reference range in viral meningitis, but it may be low in some cases of LCM, HSV, mumps virus, or
poliovirus infection.
The CSF protein level (reference range, 20-50 mg/dL) is usually elevated in bacterial meningitis. In viral meningitis, these
levels are also usually elevated, though they can be within the reference range. In syphilitic meningitis, abnormal CSF
protein levels (elevated) and CSF glucose levels (decreased) may be observed in 10-70% of cases.
CSF Gram stain and acid-fast bacillus stain
Gram staining of the CSF permits rapid identification of the bacterial cause in 60-90% of patients with bacterial meningitis.
The presence of bacteria is 100% specific, but the sensitivity of this test for detection is variable. The likelihood of detection
is higher in the presence of a higher bacterial concentration and diminishes with prior antibiotic use.
The demonstration of AFB (eg, with auramine-rhodamine stain, Ziehl-Neelsen stain, or Kinyoun stain) in the CSF is difficult
and usually requires a large volume of CSF. Meningeal biopsy, with the demonstration of caseating granulomas and AFB on
the smear, offers a higher yield than the CSF AFB smear.
CSF culture and antigen testing
CSF bacterial cultures yield the bacterial cause in 70-85% of cases. The yield diminishes by 20% in patients who have
received antimicrobial therapy. In these cases, some experts advocate the use of a CSF bacterial antigen assay. This is a
latex agglutination technique that can detect the antigens of H influenzae type B (Hib), S pneumoniae, N meningitidis, E coli
K1, and S agalactiae (group B streptococcus [GBS]). Its theoretical advantage is the detection of the bacterial antigens even
after microbial killing, as is observed after antibacterial therapy.
Another attractive alternative is using the Binax NOW for S pneumoniae in the CSF. This assay has a 99-100% sensitivity
and specificity for ruling out the most common cause of bacterial meningitis.[25]
Others studies, however, have shown that the CSF bacterial antigen assay may not be better than the Gram stain. Although
it is specific (a positive result indicates a diagnosis of bacterial meningitis), a negative finding on the bacterial antigen test
does not rule out meningitis (50-95% sensitivity).
Cryptococcal meningitis
C neoformans may be cultured from the CSF in cryptococcal meningitis. Other methods of identification include India ink
preparation and the detection of CSF cryptococcal antigen. India ink has a sensitivity of only 50%, but it is highly diagnostic if
positive.
Because of the low sensitivity of the India ink preparation, many centers have adapted the use of CSF cryptococcal antigen
determination, a test with a sensitivity exceeding 90%. However, the CSF cryptococcal antigen determination is not
universally available.
In instances when the India ink results are negative but the degree of clinical suspicion for cryptococcal meningitis is high,
the CSF specimen may be sent to reference laboratories that can perform CSF cryptococcal antigen determination to
confirm the diagnosis. In addition, the titer of the antigen could serve to monitor the response to treatment. Blood cultures
and serum cryptococcal antigen should be obtained to determine whether cryptococcal fungemia is present.
Syphilitic meningitis
In syphilitic meningitis, isolating T pallidum from the CSF is extremely difficult and time-consuming. The spirochete could be
demonstrated by using dark-field or phase-contrast microscopy on specimens collected from skin lesions (eg, chancres and
other syphilitic lesions).
The diagnosis is usually supported by the CSF VDRL test, which has a sensitivity of 30-70% (a negative result on the CSF
VDRL test does not rule out syphilitic meningitis) and a high specificity (a positive test result suggests the disease). Care
must always be taken not to contaminate the CSF with blood during spinal fluid collection (eg, traumatic tap).
Lyme meningitis
CSF culture for B burgdorferi has a low yield. The CSF Lyme PCR assay, if available, offers a rapid, sensitive, and specific
method of diagnosis. This assay is gaining popularity as the method of choice for diagnosing Lyme meningitis.
Cohn et al validated a clinical prediction rule for differentiating Lyme meningitis from aseptic meningitis. Their “rule of 7s”
classifies children at low risk for Lyme meningitis when all of the following 3 criteria are met[30] :
< 7 days of headache
< 70% CSF mononuclear cells
Absence of cranial nerve VII palsy or other cranial nerve palsy
Culture for Mycobacterium usually takes several weeks and may delay definitive diagnosis. M tuberculosis detection assays
involving nucleic acid amplification have become available and have the advantages of rapidity, high sensitivity, and high
specificity. There remains a need for mycobacterial growth in cultures because this method offers the advantage of
performing drug susceptibility assays.
Viral isolation from CSF
Isolation of viruses from the CSF has a sensitivity of 65-70% for enteroviruses. Alternatively, isolation of enteroviruses from
throat and stool viral cultures may also indirectly implicate enterovirus as the cause of the meningitis. Culture of mumps virus
from the CSF has a low sensitivity (30-50%). LCM virus may be cultured in blood early in the disease or in urine at a later
stage.
Neuroimaging
Computed tomography (CT) of the head and magnetic resonance imaging (MRI) of the brain generally do not aid in the
diagnosis of meningitis. Some patients may show meningeal enhancement, but its absence does not rule out the condition.
Routinely obtaining CT scans of the head may lead to unnecessary delay in the performance of diagnostic lumbar puncture
and the initiation of antibiotic therapy; the latter may be detrimental to the outcome in these patients.
Cerebral herniation following the lumbar tap procedure is rare in individuals with no focal neurologic deficits and no evidence
of increased ICP. If it occurs, it usually does so within 24 hours after the LP; thus, herniation should always be considered in
the differential diagnosis if the patient’s neurologic status deteriorates during that time frame.
According to the Infectious Diseases Society of America guidelines, the following are indications for screening head CT
before LP in adult patients[23] :
Immunocompromised state
History of CNS disease (eg, mass lesion, stroke, or focal infection)
Seizure within 1 week of presentation
Papilledema
Abnormal level of consciousness
Focal neurologic deficit (eg, dilated nonreactive pupil, gaze palsy, or arm or leg drift)
In patients with suspected bacterial meningitis, blood cultures should be obtained and treatment initiated before imaging
studies and LP. Neuroimaging may yield normal results or demonstrate small ventricles, effacement of sulci, and contrast
enhancement over convexities (see the images below). Late findings include venous infarction and communicating
hydrocephalus. Brain abscess, sinus or mastoid infection, skull fracture, and congenital anomalies must be ruled out. (See
Imaging in Bacterial Meningitis.)
Acute bacterial meningitis. This axial nonenhanced computed tomography scan shows mild ventriculomegaly and sulcal
effacement.
Acute bacterial meningitis. This axial T2-weighted magnetic resonance image shows only mild ventriculomegaly.
Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted magnetic resonance image shows leptomeningeal
enhancement (arrows).
Finally, neuroimaging studies are helpful in the detection of CNS complications of bacterial meningitis, such as the following
(see the images below):
Hydrocephalus
Cerebral infarct
Brain abscess
Subdural empyema
Venous sinus thrombosis
Chronic mastoiditis and epidural empyema in a patient with bacterial meningitis. This axial computed tomography
scan shows sclerosis of the temporal bone (chronic mastoiditis), an adjacent epidural empyema with marked dural
enhancement (arrow), and the absence of left mastoid air.
Subdural empyema and arterial infarct in a patient with bacterial meningitis. This contrast-enhanced axial computed
tomography scan shows left-sided parenchymal hypoattenuation in the middle cerebral artery territory, with marked
herniation and a prominent subdural empyema.
Treatment
Approach Considerations
If the patient is in shock or hypotensive, crystalloid should be infused until euvolemia is achieved. If the patient’s mental
status is altered, seizure precautions should be considered, seizures should be treated according to the usual protocol, and
airway protection should be considered. If the patient is alert and in stable condition with normal vital signs, oxygen should
be administered, intravenous (IV) access established, and rapid transport to the emergency department (ED) initiated.
Institution of an ED triage protocol may help identify patients at risk.
In acute meningitis, regardless of presentation, a lumbar puncture (LP) and cerebrospinal fluid (CSF) examination are
indicated to identify the causative organism and, in bacterial meningitis, the antibiotic sensitivities. Computed tomography
(CT) of the head should be performed a before LP, if indicated. If no mass effect is present on head CT, LP is performed to
obtain microbiology studies.
The performance of radiographic imaging should not delay the initiation of empiric antimicrobial therapy; such therapy should
be initiated before head CT if indicated. It is vital to begin treatment as early as possible in the disease course; delay may
contribute significantly to morbidity and mortality. In acutely ill patients, antibiotic therapy should be initiated promptly; in
many of these cases, one should strongly consider giving adjunctive dexamethasone before the first antibiotic dose, or at
least concomitantly with the dose.[23]
The patient’s condition and ED organization may warrant 8-12 hours of watchful waiting, followed by reexamination of the
CSF (this should be done sooner if the patient’s condition deteriorates). If initial granulocytosis changes to mononuclear
predominance, CSF glucose remains normal, and the patient continues to look well, the infection is most likely nonbacterial.
Treatment of complications
Systemic complications of acute bacterial meningitis must be treated, including the following:
Hypotension or shock
Hypoxemia
Hyponatremia (from syndrome of inappropriate antidiuretic hormone secretion [SIADH])
Cardiac arrhythmias and ischemia
Stroke
Exacerbation of chronic diseases
Signs of hydrocephalus and increasing intracranial pressure (ICP) should be watched for. Fever and pain should be
managed, straining and coughing controlled, seizures prevented, and systemic hypotension avoided. In otherwise stable
patients, sufficient care includes elevating the head and monitoring neurologic status. When more aggressive maneuvers are
indicated, some authorities favor early use of diuresis (ie, furosemide 20 mg IV or mannitol 1 g/kg IV), provided that
circulatory volume is protected.
Hyperventilation in intubated patients, with an arterial carbon dioxide tension (PaCO2) of 25-30 mm Hg as the goal, may
briefly lower ICP; hyperventilation to a PaCO2 lower than 25 mm Hg may decrease cerebral blood flow disproportionately
and lead to CNS ischemia. Placement of an ICP monitor should be considered in comatose patients or those with signs of
increased ICP. With elevated ICP, CSF should be removed until pressure decreases by 50%; ICP should then be maintained
at less than 300 mm H2 O.
Because seizure activity increases ICP, seizures must be aggressively controlled if present. Control may be accomplished by
giving lorazepam 0.1 mg/kg IV and IV load with phenytoin 15 mg/kg or phenobarbital 5-10 mg/kg.
Treatment of Subacute Meningitis

Patients with subacute meningitis (duration of symptoms >5 days prior to presentation) are more commonly
immunosuppressed, have comorbidities, have fungal etiologies, have higher rates of hypoglycorrhachia, and have abnormal
neurological findings than patients with acute meningitis.[31] Furthermore, patients with subacute meningitis are less likely to
be treated empirically with intravenous antibiotics and have lower levels of CSF pleocytosis and serum WBC counts than
patients with acute meningitis.
Treatment of Bacterial Meningitis
Bacterial meningitis (including meningococcal meningitis, Haemophilus influenzae meningitis, and staphylococcal meningitis)
is a neurologic emergency that is associated with significant morbidity and mortality. Initiation of empiric antibacterial therapy
is therefore essential for better outcome.[32, 33] (See tables 7 and 8 below.)
Table 7. Recommended Empiric Antibiotics for Suspected Bacterial Meningitis, According to Age or Predisposing Factors [33]
(Open Table in a new window)
Age or Predisposing Feature Antibiotics
Age 0-4 wk Ampicillin plus either cefotaxime or an aminoglycoside
Age 1 mo-50 y Vancomycin plus cefotaxime or ceftriaxone*
Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus

Age >50 y
vancomycin*
Impaired cellular immunity Vancomycin plus ampicillin plus either cefepime or meropenem
Recurrent meningitis Vancomycin plus cefotaxime or ceftriaxone
Basilar skull fracture Vancomycin plus cefotaxime or ceftriaxone
Head trauma, neurosurgery, or CSF

Vancomycin plus ceftazidime, cefepime, or meropenem
shunt
CSF = cerebrospinal fluid.
*Add ampicillin if Listeria monocytogenes is a suspected pathogen.
Table 8. Specific Antibiotics and Duration of Therapy for Acute Bacterial Meningitis (Open Table in a new window)
Duration
Bacteria Susceptibility Antibiotic(s)
(days)
Streptococcus Recommended: Penicillin G or ampicillin 10-14

pneumoniae Penicillin MIC ≤0.06
μg/mL Alternatives: Cefotaxime, ceftriaxone,
chloramphenicol
Penicillin MIC ≥0.12 Recommended: Cefotaxime or ceftriaxone

μg/mL
Cefotaxime or Alternatives: Cefepime, meropenem
ceftriaxone MIC ≥0.12
μg/mL
Cefotaxime or Recommended: Vancomycin plus cefotaxime or

ceftriaxone MIC ≥1.0 ceftriaxone
μg/mL
Alternatives: Vancomycin plus moxifloxacin
Recommended: Ampicillin
Beta-
lactamase−negative Alternatives: Cefotaxime, ceftriaxone, cefepime,
chloramphenicol, aztreonam, a fluoroquinolone
Recommended: Cefotaxime or ceftriaxone

Haemophilus
Beta-lactamase−positive 7
influenzae Alternatives: Cefepime, chloramphenicol, aztreonam,
a fluoroquinolone
Beta- Recommended: Meropenem

lactamase−negative,
Alternatives: Cefepime, chloramphenicol, aztreonam,
ampicillin-resistant
a fluoroquinolone
Recommended: Penicillin G or ampicillin

Penicillin MIC < 0.1
μg/mL Alternatives: Cefotaxime, ceftriaxone,
chloramphenicol
Neisseria
7
meningitidis
Penicillin MIC ≥0.1
μg/mL Alternatives: Cefepime, chloramphenicol, a
fluoroquinolone, meropenem
Listeria Recommended: Ampicillin or penicillin G

... 14-21
monocytogenes
Alternative: TMP-SMX
Streptococcus Recommended: Ampicillin or penicillin G

... 14-21
agalactiae
Alternatives: Cefotaxime, ceftriaxone, vancomycin

Enterobacteriaceae ... 21
Alternatives: Aztreonam, a fluoroquinolone, TMP-
SMX, meropenem, ampicillin
Pseudomonas ... Recommended: Ceftazidime or cefepime 21

aeruginosa Alternatives: Aztreonam, meropenem, ciprofloxacin
Recommended: Vancomycin
Staphylococcus
Alternative: Linezolid
epidermidis
Consider addition of rifampin
MIC= minimal inhibitory concentration; TMP-SMX = trimethoprim-sulfamethoxazole.
It is vital to institute empiric antimicrobial therapy (ie, antibacterial treatment or, in selected cases, antiviral or antifungal
therapy) as soon as possible. The choice of agents is usually based on the known predisposing factors, initial CSF Gram
stain results, or both. Once the pathogen has been identified and antimicrobial susceptibilities determined, the antibiotics
may be modified for optimal targeted treatment.
Bacterial resistance, especially penicillin resistance among S pneumoniae strains, has been increasing worldwide. In March
2008, the US Food and Drug Administration (FDA) revised the susceptibility breakpoints for penicillin versus S pneumoniae.
For nonmeningeal infections, the breakpoints are as follows:
< 2 µg/mL – Susceptible
4 µg/mL – Intermediate
>8 µg/mL – Resistant
For meningitis, the breakpoints are as follows:
< 0.06 µg/mL – Susceptible
≥0.12 µg/mL – Resistant
With the new meningitis criteria (≥0.12 μg/mL), the prevalence of resistance was 34.8% in 2008, whereas with the old criteria
(≥2 μg/mL), it was 12.3% for CSF.[34] The geographic distribution of this resistance is variable, and it is important to know
the regional patterns when deciding on local empiric antibiotic therapy (see Medication). A large observational study of 548
pneumococcal meningitis cases from Brazil showed that penicillin resistance was associated with higher mortality even after
adjustment for age and severity of illness.[35]
Appropriate antibiotic treatment for the most common types of bacterial meningitis reduces the risk of death. Mortality is
higher with pneumococcal meningitis. In a nationwide observational cohort study from The Netherlands, adjunctive use of
dexamethasone decreased pneumococcal meningitis mortality from 30% to 20%.[36]
The chosen antibiotic should attain adequate levels in the CSF, and its ability to do so usually depends on its lipid solubility,
molecular size, and protein-binding capacity, as well as on the patient’s degree of meningeal inflammation. The penicillins,
certain cephalosporins (ie, third- and fourth-generation agents), the carbapenems, fluoroquinolones, and rifampin provide
high CSF levels.
Monitoring for possible drug toxicity during treatment (eg, with blood counts and renal and liver function monitoring) is
warranted. The antimicrobial dose must be adjusted on the basis of the patient’s renal and hepatic function. At times,
obtaining serum drug concentrations may be necessary to ensure adequate levels and to avoid toxicity in drugs with a
narrow therapeutic index (eg, vancomycin and aminoglycosides). The patient must also be monitored for complications from
the disease (eg, hydrocephalus, seizures, or hearing defects).
Antibiotic therapy: neonates to age 1 month
In the first month of life, the most common microorganisms are group B or D streptococci, Enterobacteriaceae (eg, E coli),
and L monocytogenes. Primary treatment consists of a combination of ampicillin and cefotaxime. The recommended dosage
for cefotaxime is 50 mg/kg IV every 6 hours, up to 12 g/day. Ampicillin dosages are as follows:
Age 0-7 days – 50 mg/kg IV every 8 hours
Age 8-30 days – 50-100 mg/kg IV every 6 hours
Alternative treatment consists of ampicillin plus gentamicin. Gentamicin dosages are as follows:
Age 0-7 days – 2.5 mg/kg IV or intramuscularly (IM) every 12 hours

Age 8-30 days – 2.5 mg/kg IV or IM every 8 hours
Most authorities recommend adding acyclovir 10 mg/kg IV every 8 hours for herpes simplex encephalitis.
Antibiotic therapy: age 1-3 months
In infants 1-3 months of age, the first-line agent is cefotaxime (50 mg/kg IV every 6 hours, up to 12 g/day) or ceftriaxone (75
mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day) plus ampicillin (50-100 mg/kg IV every 6 hours). An alternative
agent is chloramphenicol (25 mg/kg orally or IV every 12 hours) plus gentamicin (2.5 mg/kg IV or IM every 8 hours).
If the local prevalence of drug-resistant S pneumoniae (DRSP) is higher than 2%, vancomycin (15 mg/kg IV every 8 hours)
should be added. Treatment with dexamethasone (0.4 mg/kg IV every 12 hours for 2 days or 0.15 mg/kg IV every 6 hours for
4 days) should be strongly considered, starting 15-20 minutes before the first dose of antibiotics.
Antibiotic therapy: age 3 months to 7 years
In older infants or young children (age 3 months to 7 years), the most common microorganisms are S pneumoniae, N
meningitidis, and H influenzae. Primary treatment is with either cefotaxime (50 mg/kg IV every 6 hours, up to 12 g/day) or
ceftriaxone (75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day).
If the prevalence of DRSP is greater than 2%, vancomycin (15 mg/kg IV every 8 hours) should be added. In countries with a
low prevalence of DRSP, penicillin G (250,000 units/kg/day IM or IV in 3-4 divided doses) may be considered. Because of
the increasing prevalence of DRSP, penicillin G is no longer recommended in the United States.
An alternative (which may also be chosen if the patient is severely allergic to penicillin) is chloramphenicol (25 mg/kg orally
or IV every 12 hours) plus vancomycin (15 mg/kg IV every 8 hours). Treatment with dexamethasone (0.4 mg/kg IV every 12
hours for 2 days or 0.15 mg/kg IV every 6 hours for 4 days) should be strongly considered, starting 15-20 minutes before the
first dose of antibiotics.
Antibiotic therapy: age 7-50 years
In an older child or an otherwise healthy adult (age 7-50 years), the most common microorganisms in bacterial meningitis
are S pneumoniae, N meningitidis, and L monocytogenes. In areas where the prevalence of DRSP is greater than 2%,
primary treatment consists of with either cefotaxime or ceftriaxone plus vancomycin. Pediatric dosing is as follows:
Cefotaxime – 50 mg/kg IV every 6 hours, up to 12 g/day
Ceftriaxone – 75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day
Vancomycin – 15 mg/kg IV every 8 hours
Adult dosing is as follows:
Cefotaxime – 2 g IV every 4 hours
Ceftriaxone – 2 g IV every 12 hours
Vancomycin – 750-1000 mg IV every 12 hours or 10-15 mg/kg IV every 12 hours
Some experts add rifampin (pediatric dose, 20 mg/kg/day IV; adult dose, 600 mg/day orally). If Listeria is suspected,
ampicillin (50 mg/kg IV every 6 hours) is added.
An alternative (which may also be chosen if the patient is severely penicillin-allergic) is chloramphenicol (12.5 mg/kg IV
every 6 hours; not bactericidal) or clindamycin (pediatric dose, 40 mg/kg/day IV in 3-4 doses; adult dose, 900 mg IV every 8
hours; active in vitro but no clinical data) or meropenem (pediatric dose, 20-40 mg/kg IV every 8 hours; adult dose, 1 g IV
every 8 hours; active in vitro but few clinical data). Imipenem is a proconvulsant and must be avoided.
In areas with a low prevalence of DRSP, cefotaxime or ceftriaxone plus ampicillin is recommended. Pediatric dosing is as
follows:
Cefotaxime – 50 mg/kg IV every 6 hours, up to 12 g/day
Ceftriaxone – 75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day
Ampicillin – 50 mg/kg IV every 6 hours
Adult dosing is as follows:
Cefotaxime – 2 g IV every 4 hours
Ceftriaxone – 2 g IV every 12 hours
Ampicillin – 50 mg/kg IV every 6 hours
An alternative (which may also be chosen if the patient is severely penicillin-allergic) is chloramphenicol (12.5 mg/kg IV
every 6 hours) plus trimethoprim-sulfamethoxazole (TMP-SMX; TMP 5 mg/kg IV every 6 hours) or meropenem (pediatric
dose, 20-40 mg/kg IV every 8 hours; adult dose, 1 g IV every 8 hours).
Data on the need for dexamethasone treatment in adults are limited, though there is support for its use in developed
countries when S pneumoniae is the suspected organism. The first dose of dexamethasone (0.4 mg/kg every 12 hours IV for
2 days or 0.15 mg/kg every 6 hours for 4 days) should be administered 15-20 minutes before the first dose of antibiotics.
Antibiotic therapy: age ≥50 years
In adults older than 50 years or adults with disabling disease or alcoholism, the most common microorganisms are S
pneumoniae, coliforms, H influenzae, Listeria species, P aeruginosa, and N meningitidis.
Primary treatment, if the prevalence of DRSP is greater than 2%, is with either cefotaxime (2 g IV every 4 hours) or
ceftriaxone (2 g IV every 12 hours) plus vancomycin (750-1000 mg IV every 12 hours or 10-15 mg/kg IV every 12 hours). If
the CSF Gram stain shows gram-negative bacilli, ceftazidime (2 g IV every 8 hours) is given. In areas of low DRSP
prevalence, treatment consists of cefotaxime (2 g IV every 4 hours) or ceftriaxone (2 g IV every 12 hours) plus ampicillin (50
mg/kg IV every 6 hours). Other options are meropenem, TMP-SMX, and doxycycline.
The Infectious Diseases Society of America guidelines recommend adjunctive dexamethasone in patients with suspected or
proven community-acquired bacterial meningitis, but only in high-income countries.[23] The first dose of dexamethasone (0.4
mg/kg IV every 12 hours for 2 days or 0.15 mg/kg every 6 hours for 4 days) is given 15-20 minutes before the first dose of
antibiotics.
Dexamethasone should be continued if the culture grows either S pneumoniae or H influenzae. However, some experts
advise that adjunctive treatment should be continued irrespective of the causative bacterium because of the low incidence of
adverse events.
Antibiotic therapy: HIV-infected patients
In HIV-infected patients, if an ED workup does not identify a pathogen, serum and CSF samples should be drawn for
cryptococcal antigen testing. Empiric treatment should proceed as in adults older than 50 years (pending results of all blood
and CSF tests) to cover the bacterial pathogens, particularly S pneumoniae and L monocytogenes, for which this patient
population is most at risk. (See Meningitis in HIV.)
Steroid therapy
The use of corticosteroids (typically, dexamethasone, 0.15 mg/kg every 6 hours for 2-4 days) as adjunctive treatment for
bacterial meningitis improves outcome by attenuating the detrimental effects of host defenses (eg, inflammatory response to
the bacterial products and the products of neutrophil activation). Controversy surrounds this practice, however, in that
dexamethasone may interrupt the cytokine-mediated neurotoxic effects of bacteriolysis, which are at maximum in the first
days of antibiotic use.[37]
Theoretically, the anti-inflammatory effects of steroids decrease blood-brain barrier permeability and impede penetration of
antibiotics into CSF. Decreased CSF levels of vancomycin have been confirmed in steroid-treated animals but not in
comparably treated humans. Many authorities believe that all other antibiotics achieve minimal inhibitory concentrations
(MICs) in CSF regardless of steroid use, and even vancomycin may not be affected to a clinically significant extent.
Nevertheless, the use of steroids has been shown to improve the overall outcome of patients with certain types of bacterial
meningitis, including H influenzae, tuberculous, and pneumococcal meningitis.
In a meta-analysis by Brouwer et al, corticosteroids significantly reduced hearing loss and neurologic sequelae but did not
reduce overall mortality. However, there was a trend toward lower mortality in adults receiving corticosteroids, and subgroup
analyses showed that corticosteroids reduced severe hearing loss in H influenzae meningitis and reduced mortality in S
pneumoniae meningitis. However, the investigators found no beneficial effect for patients in low-income countries.[38]
On the other hand, a meta-analysis of individual patient data by van de Beek et al was unable to identify which patients were
most likely to benefit from dexamethasone treatment; indeed, no significant reduction in death or neurologic disability was
found in any subgroups, including those determined by specific causative organisms, predexamethasone antibiotic
treatment, HIV status, or age. The researchers concluded that the benefits of adjunctive dexamethasone in bacterial
meningitis remain unproven.[39]
In developing countries, the use of oral glycerol (rather than dexamethasone) has been studied as adjunctive therapy in the
treatment of bacterial meningitis in children. In limited studies, it appears to reduce the incidence of neurologic sequelae
while causing few side effects.[40]
Intrathecal antibiotics
Intrathecal administration of antibiotics can be considered in patients with nosocomial meningitis (eg, meningitis developing
after neurosurgery or placement of an external ventricular catheter) that does not respond to IV antibiotics. Although the FDA
has not approved any antibiotics for intraventricular use, vancomycin and gentamicin are often used in this setting. Other
agents used intrathecally include amikacin, polymyxin B, and colistin.[41]
Intrathecal antibiotic dosages have been determined empirically and are adjusted on the basis of the CSF concentrations of
the agent. Typical daily doses are as follows[41] :
Vancomycin: 5-20 mg
Gentamicin: 1-2 mg in infants and children, 4–8 mg in adults
Amikacin: 30 mg (range, 5-50 mg)
Polymyxin B: 2 mg in infants and children, 5 mg in adults
Colistin (usually formulated as colistimethate sodium): 10 mg once daily or 5 mg every 12 hours
Treatment of Viral Meningitis

Most cases of viral meningitis are benign and self-limited. Often, patients need only supportive care and require no specific
therapy. In certain instances, specific antiviral therapy may be indicated, if available. Instituting antiretroviral therapy may be
necessary for patients with HIV meningitis that occurs during an acute seroconversion syndrome. In patients with immune
deficiency (eg, agammaglobulinemia), immunoglobulin replacement has been used to treat chronic enteroviral infections.
Herpes simplex meningitis
The antiviral management of HSV meningitis is controversial. Acyclovir (10 mg/kg IV every 8 hours) has been administered
for HSV-1 and HSV-2 meningitis. Some experts do not advocate antiviral therapy unless associated encephalitis is present,
because the condition is usually benign and self-limited. This is exemplified by Mollaret syndrome, a recurrent but benign
syndrome of lymphocytic pleocytosis that is now attributed to HSV.
Cytomegalovirus meningitis
Ganciclovir and foscarnet are used for cytomegalovirus (CMV) meningitis in immunocompromised hosts. Ganciclovir is given
in an induction dosage of 5 mg/kg IV every 12 hours for 21 days and a maintenance dosage of 5 mg/kg every 24 hours. Oral
valganciclovir (900 mg/day) can be used for maintenance if immunosuppression continues (as, for example, in AIDS patients
or transplant recipients). Foscarnet is given in an induction dosage of 60 mg/kg IV every 8 hours for 21 days and a
maintenance dosage of 90-120 mg/kg IV every 24 hours.
Treatment of Fungal Meningitis

Causes of fungal meningitis include the following:
Cryptococcus
C immitis
H capsulatum
Candida species
S schenckii (rarely)
Immune compromise is a predisposing factor in many of these cases and is often a consideration in the selection of
treatment regimens.
Cryptococcal meningitis
Cryptococcal meningitis is a major opportunistic infection in AIDS patients. For initial therapy in these cases, administer
amphotericin B (0.7-1 mg/kg/day IV) for at least 2 weeks, with or without flucytosine (100 mg/kg orally), in 4 divided doses.
Liposomal preparations of amphotericin B may be used in patients who either have or are predisposed to develop renal
dysfunction (amphotericin B liposome 3-4 mg/kg/day or amphotericin B lipid complex 5 mg/kg/day).
Fluconazole is given for consolidation therapy (400 mg/day for 8 weeks); itraconazole is an alternative if fluconazole is not
tolerated. For maintenance therapy, long-term administration of fluconazole (200 mg/day) is most effective in preventing
relapse (superior to itraconazole and amphotericin B at 1 mg/kg weekly). The risk of relapse is high in patients with AIDS.
In many cases, cryptococcal meningitis is complicated by increased ICP. Measuring the opening pressure during the LP is
strongly advised. Efforts should be made to reduce such pressure through repetition of LP or insertion of a lumbar drain or a
shunt. Medical maneuvers, such as administration of mannitol, have also been used.
The role of newer triazoles, such as voriconazole and posaconazole, has not been investigated. Echinocandins do not have
activity against cryptococcus.
In resource-limited areas, amphotericin B and fluconazole are the optimal agents for treatment of HIV-related acute
cryptococcal meningitis. Hence, treatment would consist of amphotericin and flucytosine, and policy makers and national
departments of health in such countries should consider adding drugs that are typically unavailable in such settings (eg,
flucytosine) for HIV treatment programs.[42] (See Meningitis in HIV.)
Induction and consolidation therapy for cryptococcal meningitis in patients who do not have AIDS and are not transplant
recipients involves giving amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day) for at least 4 weeks. Treatment
may be extended to 6 weeks in patients with neurologic complications. After this initial period, fluconazole (400 mg/day) is
given for at least 8 weeks. LP is recommended after 2 weeks to document sterilization of the CSF. If the infection persists,
longer induction therapy is recommended (6 weeks).
Solid-organ transplant recipients with cryptococcal meningitis should be treated with liposomal amphotericin B (3-4
mg/kg/day IV) or amphotericin B lipid complex (5 mg/kg/day IV) plus flucytosine (100 mg/kg/day in 4 divided doses) for at
least 2 weeks of induction therapy. This is followed by consolidation treatment with fluconazole (400-800 mg/day orally for 8
weeks) and then maintenance treatment with fluconazole (200 mg/day orally for 6-12 months).
The preferred treatment for meningitis caused by C immitis is oral fluconazole (400 mg/day). Some physicians initiate
therapy with a larger dose of fluconazole (as high as 1000 mg/day) or with a combination of fluconazole and intrathecal
amphotericin B. Itraconazole (400-600 mg/day) has been reported to be comparably effective. Lifelong treatment is usually
required. (See Coccidioidomycosis.)
Histoplasma capsulatum
The recommended treatment for H capsulatum meningitis is liposomal amphotericin B (5 mg/kg/day IV for a total of 175
mg/kg given over 4-6 weeks), followed by oral itraconazole (200-300 mg 2 or 3 times daily for at least 1 year or until the
resolution of CSF abnormalities and Histoplasma antigen levels). Blood levels of itraconazole should be measured to ensure
good absorption of the oral drug.
This infection is associated with a poor outcome. Approximately 20-40% of patients with meningitis succumb to the infection
despite amphotericin B therapy, and 50% of responders relapse after treatment is discontinued.
Candida species
The preferred initial therapy for candidal meningitis is amphotericin B (0.7 mg/kg/day). Flucytosine (25 mg/kg every 6 hours)
is usually added and adjusted to maintain serum levels of 40-60 µg/mL. Azoles may be used for follow-up therapy or
suppressive treatment.
The risk of relapse is high, and the duration of treatment is arbitrary. Some recommend continuing treatment for a minimum
of 4 weeks after the complete resolution of symptoms. The removal of prosthetic materials (eg, ventriculoperitoneal shunts)
is a significant component of therapy in candidal meningitis associated with neurosurgical procedures.
Sporothrix schenckii
The lipid formulation of amphotericin B is the recommended initial treatment; after the patient responds, itraconazole (200
mg twice daily) is recommended as step-down therapy and should be given to complete a total of at least 12 months of
therapy.[43] Using itraconazole to achieve lifelong suppression may be attempted after initial therapy with amphotericin B.
Fluconazole is less active against Sporothrix than itraconazole is.
Treatment of Tuberculous Meningitis

Treatment of tuberculous meningitis with a combination of first-line drugs is advocated. The selection depends on the
resistance pattern in the community and the results of susceptibility testing (once available). Isoniazid and pyrazinamide
attain good CSF levels (approximating blood levels). Rifampin penetrates the blood-brain barrier less efficiently but still
attains adequate CSF levels. Ethambutol and streptomycin may also be part of combination therapy.
The dosages of drugs for tuberculous meningitis are similar to those used for pulmonary tuberculosis, as follows:
Isoniazid 300 mg/day
Rifampin 600 mg/day
Pyrazinamide 15-30 mg/kg/day
Ethambutol 15-25 mg/kg/day
Streptomycin 7.5 mg/kg every 12 hours
The recommended duration of treatment is 9-12 months.[44]
Corticosteroid therapy is indicated for patients with stage 2 or stage 3 disease (ie, those with evidence of neurologic deficits
or deterioration in mental function). The rationale lies in the reduction of inflammatory effects associated with mycobacterial
killing by the antimicrobial agents. The agent usually chosen is dexamethasone; the recommended dose is 60-80 mg/day,
which may be tapered gradually during a span of 6 weeks.
Treatment of Syphilitic Meningitis

The treatment of choice for neurosyphilis is aqueous crystalline penicillin G (2-4 million U/day IV every 4 hours for 10-14
days), often followed with IM penicillin G benzathine (2.4 million U). An alternative is procaine penicillin G (2.4 million U/day
IM) plus probenecid (500 mg orally every 6 hours for 14 days), followed by IM benzathine penicillin G (2.4 million U). These
regimens are also used for neurosyphilis in patients with HIV infection. Because penicillin G is the treatment of choice,
penicillin-allergic patients should undergo penicillin desensitization.
After treatment, CSF examination is repeated regularly (eg, every 6 months) to document the success of therapy. Failure of
the cell count to normalize or the serologic titers to fall may warrant retreatment.
Treatment of Parasitic Meningitis

Primary amebic meningoencephalitis (PAM), caused by N fowleri, is usually fatal. The few survivors reported in the scientific
literature benefited from early diagnosis and treatment with high-dose IV and intrathecal amphotericin B or miconazole and
rifampin. More recently, miltefosine has been used to treat both N fowleri acute meningitis and Acanthamoeba chronic
meningitis, resulting in cure in some instances, and should be used in suspected cases.[45]
Treatment of helminthic eosinophilic meningitis (such as that caused by A cantonensis or G spinigerum) is largely
supportive. It includes adequate analgesia, therapeutic CSF aspiration, and the use of anti-inflammatory agents, such as
corticosteroids. Anthelmintic therapy may be contraindicated, because clinical deterioration and death may occur as a
consequence of severe inflammatory reactions to the dying worms.
Treatment of Lyme Meningitis

Ideally, neurologic complications of Lyme disease (other than Bell palsy) are treated with parenteral antibiotics. The drug of
choice is ceftriaxone (2 g/day for 14-28 days). The alternative therapy is penicillin G (20 million U/day for 14-28 days).
Doxycycline (100 mg orally or IV every 12 hours for 14-28 days) or chloramphenicol (1 g every 6 hours for 14-28 days) has
also been used. Treatment for only 10 days has been associated with a high rate of residual symptoms.
Prevention
Vaccination and chemoprophylaxis are 2 means of preventing meningitis.
H influenzae vaccine
Vaccination against H influenzae type B (Hib) is strongly recommended in susceptible individuals (though there is no
standard recommendation for H influenzae vaccination in adults). Vaccination against S pneumoniae is also strongly
encouraged for susceptible individuals, including people older than 65 years and individuals with chronic cardiopulmonary
illnesses. It is not known whether the adult use of conjugate pneumococcal vaccine decreases the incidence of S
pneumoniae meningitis.
N meningitidis serogroups A, C, Y, and W-135 vaccine
Vaccinations against encapsulated bacterial organisms (eg, S pneumoniae and N meningitidis) are encouraged for people
with functional or structural asplenia. Vaccinations should always be administered expeditiously to individuals who undergo
splenectomy.
Vaccination with quadrivalent meningococcal polysaccharide vaccine should be offered to all high-risk populations, including
those who have underlying immune deficiencies, those who travel to hyperendemic areas and epidemic areas, and those
who do laboratory work that involves routine exposure to N meningitidis. College students who live in dormitories or
residence halls are at modest risk; they should be informed about the risk and offered vaccination.
One vaccine protects against 4 strains of N meningitidis. As of February 2008, the CDC Advisory Committee on
Immunization Practices (ACIP) no longer recommends routine immunization of children with this vaccine, but the ACIP
continues to recommend routine immunization of teenagers and all children or adults at increased risk.[46]
In 2010, the ACIP issued updated recommendations for the use of meningococcal conjugate vaccines. Two
recommendations focus on the routine vaccination of adolescents and on a primary series of vaccinations of persons aged
2-55 years with certain risk factors for meningococcal infection.[47]
Regarding the routine use of vaccines in adolescents, the 2010 CDC-ACIP guidelines specifically recommend 1 dose of
meningococcal conjugate vaccine, preferably starting at 11 or 12 years. A booster dose should be given at age 16 years. If
the primary dose was at age 13-15 years, the booster can be given at age 16-18 years. No booster is needed if the primary
dose was given at age 16 years or later.[47]
Regarding specific recommendations for individuals with certain risk factors for meningococcal infection, the ACIP stated
that HIV-infected individuals aged 11-18 years should be given a primary series of 2 doses, 2 months apart. This should be
followed by a booster dose administered at age 16 years (if the primary dose was at age 11 or 12) or at age 16-18 years (if
the primary dose was at age 13-15 years). No booster is needed if the primary dose was given at age 16 years or later.[47]
Persons aged 2-55 years who have persistent complement component deficiency or asplenia (functional or anatomic) should
be given a primary series of 2 doses, 2 months apart, followed by a booster dose every 5 years. If a 1-dose primary series
was given, the booster dose should be given as soon as possible, then every 5 years thereafter.[47]
In persons aged 2-55 years with a protracted increased risk for exposure to meningitis, the 2010 ACIP guidelines
recommend a 1-dose primary series. The booster dose should be given after 3 years for children aged 2-6 years and after 5
years for persons aged 7 years or older, if the person remains at increased risk.[47]
N meningitidis serogroup B vaccine
According to the CDC, in 2012, approximately 500 cases of meningococcal disease were reported; of those, 160 resulted
from serogroup B.
In October 2014, the FDA approved the first meningococcal vaccine for serogroup B (Trumenba) under the breakthrough
therapy designation and accelerated approval regulatory pathways. Recent outbreaks of serogroup B meningococcal
disease on a few college campuses have heightened concerns for this potentially deadly disease.
Approval was based on 3 randomized trials conducted in the United States and Europe in about 2800 adolescents. Among
participants who were given 3 doses of the vaccine, 82% developed antibodies against 4 different N meningitidis serogroup
B strains representative of those that cause serogroup B meningococcal disease in the United States compared with less
than 1% before vaccination.[48]
In January 2015, a second meningococcal serogroup B vaccine was approved (Bexsero).[49]
Pneumococcal vaccine
The ACIP recommends administration of 13-valent pneumococcal polysaccharide-protein conjugate vaccine as part of
routine childhood immunization.[50] The ACIP recommends targeted use of the 23-valent pneumococcal polysaccharide
vaccine (PPSV23, formerly PPV23) in children aged 2-18 years with underlying medical conditions that increase the risk of
pneumococcal disease or complications. Vaccination against measles and mumps effectively eliminates aseptic meningitis
syndrome caused by these pathogens. In September 2014, the CDC recommended that all adults aged 65 years or older
receive both PCV13 (13-valent pneumococcal conjugate vaccine) and PPSV23 (23-valent pneumococcal polysaccharide
vaccine) as part of routine vaccination.[51]
Chemoprophylaxis
After exposure to an index case involving H influenzae, N meningitidis, or S pneumoniae, temporary nasopharyngeal
carriage of the organism is typical. An association between carriage and the risk of disease has been described, especially
for N meningitidis and H influenzae. This is the basis for the recommendations on chemoprophylaxis. However, such
prophylaxis does not treat incubating invasive disease; accordingly close monitoring of individuals at highest risk is crucial.
To eliminate nasopharyngeal carriage of Hib and to decrease invasion of colonized susceptible individuals, rifampin (20
mg/kg/day for 4 days) is given. The index patient may need chemoprophylaxis if the administered treatment does not
eliminate carriage.
Prophylaxis is suggested for contacts of persons with meningococcal meningitis (eg, household contacts, daycare center
members who eat and sleep in the same dwelling, close contacts in military barracks or boarding schools, and medical
personnel performing mouth-to-mouth resuscitation). Rifampin (600 mg PO every 12 hours for 2 days) can rapidly eradicate
the carrier stage, and the prophylaxis persists for as long as 10 weeks after treatment.
Alternative agents for adults include ceftriaxone (250 mg IM in a single dose); this agent is also the safest choice in pregnant
patients. Ceftriaxone has been shown to eradicate the carrier state for 14 days. Ciprofloxacin (500-750 mg in a single dose)
is also effective.
Consultations
Consultation with an infectious diseases specialist is indicated. Consultation with a neurosurgeon is indicated in patients with
any of the following:
Severe intracranial hypertension
Evidence of paranasal and mastoid infection that warrants surgical drainage
Skull fractures
Foreign body–associated infections (eg, ventriculoperitoneal shunts)
Associated abscess formation
Long-Term Monitoring
Vigilant surveillance for the development of complications is required in patients with meningitis. Seizure precautions are
indicated, especially for patients with impaired mental function. Proper isolation precautions are indicated in cases of
invasive meningococcal disease.
Patients must be monitored for potential adverse effects of medications, such as hypersensitivity reactions, cytopenia, or
liver dysfunction. Drug-level monitoring may be needed for some antibiotics (eg, vancomycin and the aminoglycosides).
Guidelines
Infectious Diseases Society of America Guidelines on Healthcare-Associated

Ventriculitis and Meningitis
Diagnosis
IDSA guidelines on the diagnosis of healthcare-associated ventriculitis and meningitis are as follows:[52]
New headache, fever, evidence of meningeal irritation, seizures, and/or worsening mental status suggest ventriculitis
or meningitis in the setting of recent trauma or neurosurgery.
Fever, in the absence of another clear source of infection, suggests CNS infection in the setting of recent head
trauma or neurosurgery.
New headache, nausea, lethargy, and/or change in mental status suggest CSF shunt infection.
Erythema and tenderness over the subcutaneous shunt tubing suggest CSF shunt infection.
Symptoms and signs of peritonitis or abdominal tenderness in patients with ventriculoperitoneal shunts, in the
absence of another clear etiology, indicate CSF shunt infection.
Demonstration of bacteremia in a patient with a ventriculoatrial shunt, in the absence of another clear source of
bacteremia, is evidence of CSF shunt infection.
Symptoms and signs of pleuritis in patients with ventriculopleural shunts, in the absence of another clear etiology,
indicate CSF shunt infection.
Single or multiple positive CSF culture results in patients with CSF pleocytosis and/or hypoglycorrhachia, or an
increasing cell count, and clinical symptoms suspicious for ventriculitis or meningitis, indicates CSF drain infection.
CSF cultures are the most important test to establish the diagnosis of healthcare-associated ventriculitis and
meningitis.
If initial CSF culture results are negative in patients with CSF shunts or drains with suspected infection, cultures
should be held for at least 10 days in an attempt to identify organisms such as P acnes.
Blood cultures are recommended in patients with suspected ventriculoatrial shunt infections.
CSF and blood cultures in selected patients should be obtained before the administration of antimicrobial therapy; a
negative CSF culture result in the setting of previous antimicrobial therapy does not exclude healthcare-associated
ventriculitis and meningitis.
CSF pleocytosis with a positive culture result and symptoms of infection indicate a diagnosis of healthcare-associated
ventriculitis or meningitis.
CSF cultures that grow S aureus or aerobic gram-negative bacilli indicate infection.
CSF cultures that grow a fungal pathogen indicate infection.
Neuroimaging is recommended in patients with suspected healthcare-associated ventriculitis and meningitis.
MRI with gadolinium enhancement and diffusion-weighted imaging is recommended for detecting abnormalities in
patients with healthcare-associated ventriculitis and meningitis.
In patients with infected ventriculoperitoneal shunts and abdominal symptoms (eg, pain or tenderness),
ultrasonography or CT scanning of the abdomen is recommended to detect CSF loculations at the shunt terminus.
Treatment
IDSA guidelines on the treatment of healthcare-associated ventriculitis and meningitis are as follows:[52]
Vancomycin plus an anti-pseudomonal beta-lactam (eg, cefepime, ceftazidime, or meropenem) is recommended as

empiric therapy for healthcare-associated ventriculitis and meningitis; the choice of empiric beta-lactam agent should
be based on local in vitro susceptibility patterns.
In seriously ill adult patients with healthcare-associated ventriculitis and meningitis, the vancomycin trough
concentration should be maintained at 15-20 μg/mL in those who receive intermittent bolus administration.
For patients with healthcare-associated ventriculitis and meningitis who have experienced anaphylaxis to beta-lactam
antimicrobial agents and in whom meropenem is contraindicated, aztreonam or ciprofloxacin is recommended for
gram-negative coverage.
For treatment of infection caused by methicillin-susceptible S aureus (MSSA), nafcillin or oxacillin is recommended. If
the patient cannot receive beta-lactam agents, the patient can be desensitized or may receive vancomycin as an
alternative agent.
For treatment of infection caused by methicillin-resistant S aureus (MRSA), vancomycin is recommended as first-line
therapy, with consideration for an alternative antimicrobial agent if the vancomycin minimal inhibitory concentration
(MIC) is ≥1 μg/mL.
Infections caused by S aureus or gram-negative bacilli with or without significant CSF pleocytosis, CSF
hypoglycorrhachia, or clinical symptoms or systemic features should be treated for 10-14 days (strong, low); some
experts suggest treatment of infection caused by gram-negative bacilli for 21 days.
For treatment of infection caused by coagulase-negative staphylococci, the recommended therapy should be similar
to that for S aureus and based on in vitro susceptibility testing.
Rifampin is recommended as part of combination therapy for any patient with intracranial or spinal hardware such as
a CSF shunt or drain.
For treatment of patients with healthcare-associated ventriculitis and meningitis caused by staphylococci in whom
beta-lactam agents or vancomycin cannot be used, linezolid, daptomycin, or trimethoprim-sulfamethoxazole is
recommended, with selection of a specific agent based on in vitro susceptibility testing.
For treatment of infection caused by P acnes, penicillin G is recommended.
Infections caused by a coagulase-negative Staphylococcus or P acnes with no or minimal CSF pleocytosis, normal
CSF glucose, and few clinical symptoms or systemic features should be treated for 10 days.
Infections caused by a coagulase-negative Staphylococcus or P acnes with significant CSF pleocytosis, CSF
hypoglycorrhachia, or clinical symptoms or systemic features should be treated for 10-14 days.
For treatment of infection caused by gram-negative bacilli susceptible to third-generation cephalosporins, ceftriaxone
or cefotaxime is recommended.
For treatment of infection caused by Pseudomonas species, the recommended therapy is cefepime, ceftazidime, or
meropenem; recommended alternative antimicrobial agents are aztreonam or a fluoroquinolone with in vitro activity.
For treatment of infection caused by Acinetobacter species, meropenem is recommended; for strains that
demonstrate carbapenem resistance, colistimethate sodium or polymyxin B (either agent administered by the
intravenous and intraventricular routes) is recommended.
Prolonged infusion of meropenem (each dose administered over 3 hours) may be successful in treating resistant
gram-negative organisms.
For treatment of infection caused by Candida species, based on in vitro susceptibility testing, liposomal amphotericin
B, often combined with 5-flucytosine, is recommended; once the patient shows clinical improvement, therapy can be
changed to fluconazole if the isolated species is susceptible.
For treatment of infection caused by Aspergillus or Exserohilum species, voriconazole is recommended.
When antimicrobial therapy is administered via a ventricular drain, the drain should be clamped for 15-60 minutes to
allow the agent to equilibrate throughout the CSF.
Dosages and intervals of intraventricular antimicrobial therapy should be adjusted based on CSF antimicrobial
concentrations to 10-20 times the MIC of the causative microorganism, ventricular size, and daily output from the
ventricular drain.
In patients with repeatedly positive CSF cultures on appropriate antimicrobial therapy, treatment should be continued
for 10-14 days after the last positive culture.
Medication
Medication Summary
Begin empiric antibiotic coverage according to age and presence of overriding physical conditions. Empiric therapy also
depends on prevalence of cephalosporin-resistant S pneumoniae (DRSP). In the United States, prevalence is considered
high (>2-5%). Patients with severe penicillin (and presumed cephalosporin) allergies often require alternative therapy.
Sulfonamides
Class Summary
Empiric antimicrobial therapy should cover all likely pathogens in the context of this clinical setting. Trimethoprim-
sulfamethoxazole (TMP-SMX) is effective against many aerobic gram-positive and gram-negative bacteria, but its use in
bacterial meningitis is limited to patients with Listeria monocytogenes meningitis who have a penicillin allergy.
Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

Trimethoprim and sulfamethoxazole work together to inhibit bacterial synthesis of tetrahydrofolic acid. Trimethoprim prevents
the formation of tetrahydrofolic acid by binding to bacterial dihydrofolate reductase. Sulfamethoxazole inhibits bacterial
synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. This results in
inhibition of bacterial replication.
Tetracyclines
Class Summary
Tetracyclines inhibit protein synthesis and, therefore, bacterial growth by binding with 30S and possibly 50S ribosomal
subunits of susceptible bacteria. They are broad-spectrum bacteriostatic antibiotics that are used to treat infections caused
by many gram-positive and gram-negative bacteria. They are contraindicated in children younger than 8 years of age,
because they can cause tooth discoloration and bone growth retardation.
Doxycycline (Doryx, Adoxa, Doxy 100, Monodox, Oracea)
Doxycycline can be administered twice daily and is available in both intravenous (IV) and oral formulations. It is less likely to
cause photosensitivity than other tetracyclines are. The maximum serum concentration of an IV dose of doxycycline occurs
within 30 minutes of administration. The use of doxycycline in meningitis is limited to cases of Brucella or rickettsial
meningitis.
Carbapenems
Class Summary
Carbapenems inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins. Carbapenems, including
meropenem, can be used for the treatment of meningitis.
Meropenem (Merrem IV)

A broad-spectrum carbapenem antibiotic, meropenem inhibits cell wall synthesis and has bactericidal activity. It is effective
against most gram-positive and gram-negative bacteria. Compared with imipenem, meropenem has slightly increased
activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci. It also has
limited activity against highly-penicillin-resistant S pneumoniae isolates.[43]
Fluoroquinolones
Class Summary
Fluoroquinolones inhibit bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase and topoisomerases,
which are required for replication, transcription, and translation of genetic material. The use of fluoroquinolones is not
recommended in patients with myasthenia gravis.
Second-generation fluoroquinolones, such as gatifloxacin and moxifloxacin, have excellent cerebrospinal fluid (CSF)
penetration, and animal models suggest that they are effective in penicillin- and ceftriaxone-resistant pneumococcal
meningitis. (Clinical trial data are available only for trovafloxacin, which has been removed from the market.)
Ciprofloxacin (Cipro, Cipro XR)

Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity
against anaerobes. Ciprofloxacin has an off-label indication for prophylaxis against Neisseria meningitidis meningitis after
close contact with an infected person.
Moxifloxacin (Avelox)
Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Infectious Diseases Society of
America guidelines recommend moxifloxacin plus vancomycin as an alternative to third-generation cephalosporins in
meningitis caused by penicillin- and ceftriaxone-resistant S pneumoniae strains.[17]
Antibiotics, Miscellaneous
Class Summary
Chloramphenicol inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
Chloramphenicol
Chloramphenicol is effective against gram-negative and gram-positive bacteria. It can be used as a substitute in the
treatment of a meningococcal infection in penicillin-allergic patients. Worldwide, however, meningococcal strains have shown
increasing resistance to chloramphenicol, and patients with pneumococcal meningitis have poor outcomes with
chloramphenicol.
Glycopeptides
Class Summary
Vancomycin inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization. It is indicated for many infections
caused by gram-positive bacteria.
Vancomycin
Vancomycin is a glycopeptide antibiotic that is active against staphylococci, streptococci, and other gram-positive bacteria. It
exerts antibacterial activity by inhibiting biosynthesis of peptidoglycan and is the drug of choice for highly penicillin-resistant
and ceftriaxone-resistant S pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). It is a component of
empiric first-line therapy for meningitis associated with central nervous system (CNS) shunts.
Because of poor CSF penetration, a higher dose of vancomycin is required for meningitis than for other infections. In
patients with renal impairment, the dose is adjusted on the basis of the creatinine clearance.
Aminoglycosides
Class Summary
Aminoglycosides primarily act by binding to 16S ribosomal RNA within the 30S ribosomal subunit. They have mainly
bactericidal activity against susceptible aerobic gram-negative bacilli.
Gentamicin
Although newer antibiotics are available, aminoglycosides such as gentamicin remain significant in treating severe
infections. Aminoglycosides inhibit protein synthesis by irreversibly binding to the 30S ribosomal subunit. In meningitis or
gram-negative meningitides, it must be administered intrathecally because of its poor CNS penetration. Dosing regimens are
numerous; the dose is adjusted on the basis of the creatinine clearance and changes in the volume of distribution.
Streptomycin
Streptomycin has bactericidal action and inhibits bacterial protein synthesis. Susceptible organisms include Mycobacterium
tuberculosis, Pasteurella pestis, Francisella tularensis, Haemophilus influenzae, Haemophilus ducreyi, donovanosis
(granuloma inguinale), Brucella species, Klebsiella pneumoniae, Escherichia coli, Proteus species, Aerobacter species,
Enterococcus faecalis, and Streptococcus viridans (in endocarditis, with penicillin). Streptomycin is always given as part of a
total antituberculosis regimen.
Penicillins, Amino
Class Summary
Ampicillin is a second-generation penicillin that is active against many strains of E coli, Proteus mirabilis, Salmonella,
Shigella, and H influenzae.
Ampicillin
A bactericidal beta-lactam antibiotic, ampicillin inhibits cell wall synthesis by interfering with peptidoglycan formation. The
drug is indicated for L monocytogenes and Streptococcus agalactiae (group B streptococcus [GBS]) meningitis, usually in
combination with gentamicin
Penicillins, Natural
Class Summary
Penicillins are highly active against gram-positive organisms.
Penicillin G aqueous (Crystapen, Penicillin G potassium, Penicillin G

sodium)
A beta-lactam antibiotic, penicillin G inhibits bacterial cell wall synthesis, resulting in bactericidal activity against susceptible
microorganisms. It is active against many gram-positive organisms and is the drug of choice for syphilitic meningitis and
susceptible organisms (eg, N meningitidis and penicillin-susceptible S pneumoniae).
Cephalosporins, 3rd Generation
Class Summary
Third-generation cephalosporins are less active against gram-positive organisms than first-generation cephalosporins are.
They are highly active against Enterobacteriaceae, Neisseria, and H influenzae.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against
gram-positive organisms but excellent activity against susceptible pneumococcal organisms. It exerts an antimicrobial effect
by interfering with the synthesis of peptidoglycan, a major structural component of the bacterial cell wall. It is an excellent
antibiotic for the empiric treatment of bacterial meningitis.
Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third-generation cephalosporin with broad-spectrum activity against gram-negative organisms, lower
efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more of the
penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial replication.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin that is used to treat suspected or documented bacterial meningitis caused by
susceptible organisms, such as H influenzae or N meningitidis. Like other beta-lactam antibiotics, cefotaxime inhibits
bacterial growth by arresting bacterial cell wall synthesis.
Antivirals, CMV
Class Summary
Ganciclovir can be used to treat cytomegalovirus (CMV) meningitis in immunocompromised hosts.
Ganciclovir (Cytovene)
Ganciclovir is a synthetic guanine derivative that is active against CMV. An acyclic nucleoside analog of 2′-deoxyguanosine,
it inhibits the replication of herpesviruses in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold
greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-
infected cells.
Antivirals, Other
Class Summary
Antiviral agents interfere with viral replication; they weaken or abolish viral activity. They can be used in viral meningitis.
Acyclovir (Zovirax)
A prodrug activated by cellular enzymes, acyclovir inhibits the activity of herpes simplex virus 1 (HSV-1), HSV-2, and
varicella-zoster virus (VZV) by competing for viral DNA polymerase and incorporation into viral DNA. Acyclovir is used in
HSV meningitis.
Foscarnet (Foscavir)
Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits the replication of known herpesviruses, including
CMV, HSV-1, and HSV-2. It inhibits viral replication at the pyrophosphate-binding site on virus-specific DNA polymerases.
Foscarnet is used to treat CMV meningitis in immunocompromised hosts at induction dosages of 60 mg/kg IV every 8 hours
and maintenance dosages of 90-120 mg/kg IV every 24 hours.
Antifungals, Systemic
Class Summary
Antifungal agents are used in the management of infectious diseases caused by fungi.
Amphotericin B deoxycholate (Amphotericin B (conventional), Fungizone)

A polyene antibiotic produced by a strain of Streptomyces nodosus, amphotericin B can be fungistatic or fungicidal. It binds
to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal
cell death. The drug is used to treat severe systemic infection and meningitis caused by susceptible fungi (ie, Candida
albicans, Histoplasma capsulatum, and Cryptococcus neoformans).
Amphotericin B does not penetrate the CSF well. Intrathecal amphotericin may be needed in addition.
Amphotericin B lipid complex (Abelcet)

This agent is amphotericin B in phospholipid complexed form; it is a polyene antibiotic with poor oral availability.
Amphotericin B is produced by a strain of S nodosus; it can be fungistatic or fungicidal. The drug binds to sterols (eg,
ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human
cells may occur via this same mechanism.
Fluconazole (Diflucan)
Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal
cytochrome P450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby
disrupting cellular membranes.
Flucytosine (Ancobon)
Flucytosine is converted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis by competing
with uracil. It is active against candidal and cryptococcal species and is used in combination with amphotericin B.
Itraconazole (Sporanox, Onmel)

Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting
cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Antituberculous Agents
Class Summary
These agents are used in the management of mycobacterial disease in combination with other antituberculous agents.
Rifampin (Rifadin)
Rifampin is used in combination with other antituberculous drugs. It inhibits DNA-dependent bacterial, but not mammalian,
RNA polymerase. Cross-resistance may occur.
Isoniazid
Isoniazid is a first-line antituberculous drug that is used in combination with other antituberculous drugs to treat meningitis. It
is usually administered for at least 12-24 months. Addition of pyridoxine (6-50 mg/day) is recommended if peripheral
neuropathies secondary to isoniazid therapy develop.
Pyrazinamide
Pyrazinamide is a pyrazine analogue of nicotinamide; it may be bacteriostatic or bactericidal against Mycobacterium
tuberculosis, depending on the drug concentration attained at the site of infection. Pyrazinamide's mechanism of action is
unknown.
Ethambutol (Myambutol)
Ethambutol diffuses into actively growing mycobacterial cells (eg, tubercle bacilli). It impairs cell metabolism by inhibiting the
synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated.
Mycobacterial resistance is frequent with previous therapy.
Ethambutol is used in combination with second-line drugs that have not been administered previously. It is administered
every 24 hours until permanent bacteriologic conversion and maximal clinical improvement are observed. Absorption is not
significantly altered by food.
Vaccines, Inactivated, Bacterial
Class Summary
Inactivated bacterial vaccines are used to induce active immunity against pathogens responsible for meningitis.
Meningococcal (group A C Y and W-135) diphtheria conjugate vaccine

(Menactra, Menveo)
This vaccine is composed of capsular polysaccharide antigens (groups A, C, Y, and W-135) of N meningitidis.
Meningococcal vaccine may be used to prevent and control outbreaks of serogroup C meningococcal disease, according to
Centers for Disease Control and Prevention (CDC) guidelines. It induces formation of bactericidal antibodies to
meningococcal antigens.
The vaccine is used for active immunization against invasive meningococcal disease caused by inclusive serogroups.
Although the vaccine induces antibody response for serogroup A in individuals as young as age 3 months, it is poorly
immunogenic for serogroup C in recipients who are younger than age 18-24 months.
Meningococcal group B vaccine (Trumenba, Bexsero)

The vaccine is administered as a 3-dose series at months 0, 2, and 6 (Trumenba) or a 2-dose series given at least 1 month
apart (Bexsero). It induces production of bactericidal antibodies directed against the capsular polysaccharides of serogroup
B. It is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis
serogroup B in individuals aged 10 through 25 years.
Pneumococcal polysaccharide vaccine polyvalent (Pneumovax 23)

This vaccine contains capsular polysaccharides of 23 pneumococcal types, which constitute 98% of pneumococcal disease
isolates.
Pneumococcal vaccine 13-valent (Prevnar 13)

Capsular polysaccharide vaccine against 13 strains of S pneumoniae conjugated to nontoxic diphtheria protein. Includes
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.
Corticosteroids
Class Summary
The use of steroids has been shown to improve overall outcome for patients with certain types of bacterial meningitis, such
as H influenzae, tuberculous, and pneumococcal meningitis. If steroids are given, they should be administered before or
during the administration of antimicrobial therapy.
Dexamethasone (Baycadron)
Dexamethasone has many pharmacologic benefits, such as stabilizing cell and lysosomal membranes. It increases
surfactant synthesis, increases serum vitamin A concentrations, and inhibits prostaglandin and proinflammatory cytokines
(eg, tumor necrosis factor alpha [TNF-α], interleukin [IL]-6, IL-2, and interferon gamma).
The timing of dexamethasone administration is crucial. If this agent is used, it should be administered before or with the first
dose of antibacterial therapy, so as to counteract the initial inflammatory burst consequent to antibiotic-mediated bacterial
killing. A more intense inflammatory reaction has been documented after the massive bacterial killing induced by antibiotics.
Diuretics, Osmotic Agents
Class Summary
Mannitol produces osmotic diuresis and reduces intracranial pressure (ICP).
Mannitol (Osmitrol)
Mannitol may reduce subarachnoid-space pressure by creating an osmotic gradient between CSF in the arachnoid space
and plasma. Doses of 1 g/kg IV have been used.
Diuretics, Loop
Class Summary
Loop diuretics are used to reduce ICP and treat cerebral edema.
Furosemide (Lasix)
Furosemide is a loop diuretic that increases the excretion of water by interfering with the chloride-binding cotransport
system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The
proposed mechanisms for furosemide in lowering ICP include (1) lowering cerebral sodium uptake, (2) affecting water
transport into astroglial cells by inhibiting the cellular membrane cation-chloride pump, and (3) decreasing CSF production by
inhibiting carbonic anhydrase.
Anticonvulsants, Hydantoins
Class Summary
Anticonvulsants are used to help aggressively control seizures (if present) in acute meningitis, because seizure activity
increases ICP.
Phenytoin (Dilantin, Phenytek)

Phenytoin works on the motor cortex, where it may inhibit the spread of seizure activity. The activity of brainstem centers
responsible for the tonic phase of grand mal seizures may also be inhibited. Dosing should be individualized. Doses of 15
mg/kg have been used.
Anticonvulsants, Barbiturates
Class Summary
Phenobarbital elevates the seizure threshold, limits the spread of seizure activity, and is a sedative. Doses of 5-10 mg/kg
have been recommended.
Phenobarbital
Phenobarbital elevates the seizure threshold, limits the spread of seizure activity, and is a sedative. Doses of 5-10 mg/kg
have been recommended.
Anticonvulsants, Other
Class Summary
Anticonvulsants are used to help aggressively control seizures (if present) in acute meningitis, because seizure activity
increases ICP.
Lorazepam (Ativan)
Lorazepam is a sedative hypnotic with a short onset of effect and a relatively long half-life. By increasing the action of
gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the
CNS, including the limbic system and the reticular formation. Doses of 0.1 mg/kg IV have been used to control seizures.
Questions & Answers

Overview
What is meningitis?
What are the signs and symptoms of bacterial and viral meningitis?
What should be the medical history focus when meningitis is suspected?
Which symptoms suggest enteroviral infection when meningitis is suspected?
What are signs of meningitis in infants?
What should a physical exam for meningitis include?
Which exams should be performed in chronic meningitis?
What are the signs of aseptic meningitis syndrome?
What are the diagnostic challenges in suspected meningitis?
Which blood studies are useful in the diagnosis of meningitis?
Which lab tests should be ordered in suspected meningitis?
What are the initial treatment measures that should be taken in suspected meningitis?
What are the treatment options for bacterial meningitis?
Which complications of acute bacterial meningitis must be treated initially?
In which types of meningitis is therapy dictated by the etiologic pathogen (infectious agent)?
What are the categories of infections of the central nervous system (CNS)?
Which areas of the brain and spinal cord are affected by meningitis?
What are risk factors for meningitis?
What is the clinical presentation of meningitis?
Which anatomical regions does meningitis affect?
What causes meningitis?
What is the mortality rate associated with bacterial meningitis?
How has the emergence of antibiotic-resistant bacteria changed treatment approaches for meningitis?
Which conditions may evolve from bacterial meningitis?
What are the common noninfectious causes of meningitis?
What are the subtypes of acute bacterial meningitis?
What is chronic meningitis?
How is acute meningitis differentiated from subacute or chronic meningitis?
How are fungal and parasitic meningitis classified?

What is aseptic meningitis?
Is aseptic meningitis reclassified once a cause is identified?
What is the most likely pathogenesis of meningitis?
Which pathways allow an infectious agent (pathogen) access to the central nervous system (CNS) in meningitis?
Meningitis infectious agents are spread most often through which pathway to the central nervous system (CNS)?
What are the less common ways meningitis infectious agents are transmitted to the central nervous system (CNS)?
How are meningitis infectious agents transmitted to a newborn?
How do meningitis pathogens travel from the middle ear to the meninges?
What is the role of the blood-brain barrier in the pathogenesis of meningitis?
What is the disease course of untreated bacterial meningitis?
What perpetuates the infectious process in bacterial meningitis?
What is the pathophysiology of increased intracranial pressure (ICP) in meningitis?
What is the disease course if increased intracranial pressure (ICP) due to meningitis is left untreated?
What is the disease course if cerebral edema due to meningitis is left untreated?
Which proinflammatory molecules (proteins) have a role in the pathogenesis of meningitis?
What is the role of cytokines in the pathogenesis of meningitis?
What is the role of secondary proinflammatory mediators in the pathogenesis of meningitis?
What is the cause of profound neutrophilic pleocytosis in meningitis?
What is the role of pattern recognition receptors in the pathogenesis of meningitis?
What is the role of bacterial seeding in the pathogenesis of meningitis?
How do infectious agents gain access to the subarachnoid space in meningitis?
What causes aseptic meningitis?
What are causes of meningitis?
Does HIV infection increase the risk of meningitis?
What are viral causes of meningitis?
What are the common infectious agents (pathogens) of meningitis in patients with trauma or who are undergoing
neurosurgery?
What causes pachymeningitis (perimeningitis)?
What is the role of Haemophilus influenza (H influenza) (type b) (Hib) in the development of meningitis?
What does the presence of Haemophilus influenza (H influenza) in adults with meningitis suggest?
What is the role of Streptococcus pneumoniae (S pneumoniae) in the development of meningitis?
What are the risk factors for developing Streptococcus pneumoniae (S pneumoniae) (pneumococcal) meningitis?
What is the role of Streptococcus agalactiae (group B Streptococcus) (GBS) in the transmission of neonatal meningitis?
What are the risk factors for Streptococcus agalactiae (group B Streptococcus) (GBS) meningitis in adults?
What is the role of Neisseria meningitidis (N meningitides) in the development of meningococcal meningitis?
What are risk factors for developing meningococcal meningitis?
What is the role of Listeria monocytogenes (L monocytogenes) in the development of meningitis?
Which groups are at risk for Listeria monocytogenes (L monocytogenes) meningitis?
Which aerobic gram-negative bacilli (Enterobacteriaceae) are etiologic agents of meningitis?
What are risk factors for developing meningitis caused by gram-negative bacilli (Enterobacteriaceae)?
What are risk factors for developing staphylococcal meningitis?
What is the most common cause of aseptic meningitis in children and adults?
How are enteroviruses classified?
How are enteroviruses spread?
How common are nonpolio enteroviruses (NPEVs) as a cause of viral meningitis?
What is the incidence of aseptic meningitis due to echovirus 30 (EV30)?
Which Herpesviridae (herpesviruses) cause meningitis?
Which arthropod-borne viruses cause meningitis?
Which virus causes California encephalitis?
How is lymphocytic choriomeningitis virus (LCMV) transmitted?
How common is aseptic meningitis caused by the mumps virus?
When should HIV infection be suspected as the cause of aseptic meningitis?
Which adenovirus serotypes are etiologic agents of meningoencephalitis?
When should Toscana virus (TOSV) meningitis or encephalitis be suspected?
What causes chronic meningitis?
What is the role of Brucellae in the development of meningitis?
What are the risk factors for developing brucellosis (Brucella meningitis)?
What is the role of Mycobacterium tuberculosis (M tuberculosis) in the development of meningitis?
When should tuberculous meningitis be suspected?
How is Treponema pallidum (T pallidum) transmitted?
What is the role of Borrelia burgdorferi (B burgdorferi) (Lyme disease) in the development of meningitis?
What is the role of Cryptococcus neoformans (C neoformans) in the development of meningitis?
What are the risk factors for developing coccidioidal meningitis?
What are the risk factors for Blastomyces dermatitidis (B dermatitidis) infection and how likely is it to cause meningitis?
What is the role of Histoplasma capsulatum (H capsulatum) in the development of meningitis?
What are the risk factors for developing Candida meningitis?
What are the risk factors for developing Sporothrix schenckii (S schenckii) meningitis?
How is primary amebic meningoencephalitis (PAM) transmitted?
What are the forms of primary amebic meningoencephalitis (PAM) and what are their presentations?
What are Acanthamoeba and Balamuthia granulomatous amebic encephalitis?
What is the role of Angiostrongylus cantonensis (A cantonensis) in the development of eosinophilic meningitis?
What is the role of Gnathostoma spinigerum (G spinigerum) in the development of eosinophilic meningoencephalitis?
What is the role of Baylisascaris procyonis (B procyonis) in the development of eosinophilic meningoencephalitis?
What is the role of injuries, congenital malformations, and surgeries in the development of meningitis?
Why is the incidence of meningitis higher in developing countries than in the US?
What is the incidence of bacterial meningitis in the US?

In what parts of the world is meningococcal meningitis endemic?
What is the incidence of neonatal bacterial meningitis?
Which preventive measures have decreased the incidence of bacterial meningitis in the US?
Which preventive measures have decreased the incidence of pediatric bacterial meningitis in the US?
What age groups are at highest risk for developing acute bacterial meningitis?
How does age affect risk of meningitis from specific etiologic agents?
Is bacterial meningitis more common in females or males?
What is the mortality rate associated with pneumococcal meningitis?
What is the incidence of aseptic meningitis?
What factors influence the infection rates of aseptic meningitis?
In addition to aseptic meningitis, what other disorders are caused by West Nile virus infection?
Which less-common arboviruses have caused aseptic meningitis in the US?
What is the epidemiology of lymphocytic choriomeningitis (LCM) virus infections?
What is the global distribution of fungal pathogens that cause meningitis?
What is the global distribution of parasites that cause meningitis?
What is the global distribution of Brucella chronic meningitis?
What is the global incidence of Mycobacterium tuberculosis (M tuberculosis) infection?
What is the global distribution of Borrelia burgdorferi (B burgdorferi) (Lyme disease)?
What is the global distribution of Cryptococcus neoformans (C neoformans)?
What is the global distribution of Coccidioides immitis (C immitis)?
What is the global distribution of Sporothrix schenckii (S schenckii)?
Which presentations of meningitis increase the risk for neurologic sequelae or death?
What are negative prognostic factors in adults with bacterial meningitis?
What are the serious complications of bacterial meningitis?
What are the delayed complications of pneumococcal meningitis?
How common are seizures in meningitis?
What is the incidence of neurologic complications of bacterial meningitis?
What is mortality rate associated with bacterial meningitis?
What is the prognosis of meningitis caused by opportunistic pathogens?
Which pathogens cause the highest mortality and morbidity in bacterial meningitis?
What is the prognosis for meningococcal meningitis versus pneumococcal meningitis?
What is the prognosis for viral meningitis?
What patient information (education) should be provided and to whom regarding meningitis preventive measures?
Presentation
Which atypical symptoms of meningitis may develop in infants?
What are symptoms of meningitis?
How soon do symptoms of bacterial meningitis develop?
What symptoms may precede viral meningitis?

How common are seizures in bacterial meningitis?
Which patient groups are more likely to present with atypical symptoms of meningitis?
Which factors should be assessed in cases of meningitis to help determine etiology?
What should be the focus of the medical history in suspected meningitis?
How common is bacterial meningitis following antibiotic use?
Does the presence of a ventriculoperitoneal shunt or history of cranial surgery increase the risk of bacterial meningitis?
Are alcoholism and cirrhosis risk factors for meningitis?
What role does geographic location and travel history have in the identification of meningitis etiology?
What roles do season and temperature have in the identification of meningitis etiology?
What is the classic presentation of meningitis?
How does the clinical presentation of acute bacterial meningitis differ from that of subacute bacterial meningitis?
What are possible systemic findings of meningitis?
What are expected physical findings in viral meningitis?
Which etiologies of meningitis may present with nonblanching petechiae and cutaneous hemorrhages?
What is the typical presentation of meningitis in infants?
What are the focal neurologic signs of meningitis?
When is lumbar puncture (LP) indicated in suspected meningitis?
Which systemic findings on physical exam provide clues to the etiology of meningitis?
Which physical exam findings suggest chronic meningitis?
What are the presentation and clinical stages of chronic tuberculous meningitis?
What is the presentation of syphilitic meningitis?
What is the presentation of Lyme meningitis?
What is the presentation of Cryptococcus neoformans (C neoformans) meningitis?
What is the presentation of coccidioidal meningitis?
What is the presentation of meningitis caused by Blastomyces dermatitidis (B dermatitidis) or Histoplasma capsulatum (H
capsulatum)?
What is the presentation of helminthic eosinophilic meningitis?
What is the presentation of aseptic meningitis?
What are immediate complications of meningitis?
What disorders are caused by brain parenchymal damage in bacterial meningitis?
What are the delayed complications of meningitis?
Is cerebral edema a common complication of meningitis?
What causes cranial nerve palsy and cerebral infarction in meningitis?
How does cerebritis develop in meningitis?
What are the risk factors for development of subdural effusion in meningitis?
How does ventriculitis develop in meningitis and how common is it?
How does ventriculomegaly develop in meningitis?
DDX
Which disorders should be considered in differential diagnoses of meningitis?
What are the differential diagnoses for Meningitis?
Workup
What are the diagnostic challenges of meningitis?
Why should acute bacterial meningitis be the first diagnosis considered in patients with headache, neck stiffness, fever, and
altered mental status?
Why should lumbar puncture be performed whenever meningitis is suspected?
When is a CT scan of the head indicated in suspected meningitis?
What lab tests should be performed in suspected meningitis?
What does evidence of pneumonia on initial chest X-ray indicate in suspected meningitis?
Which blood tests are useful in suspected bacterial meningitis?
When are cultures most useful for diagnosing meningitis?
When is latex agglutination or counterimmunoelectrophoresis (CIE) indicated in the evaluation of suspected meningitis?
What is the role of polymerase chain reaction (PCR) testing in the diagnosis of meningitis?
Which syphilis screening tests should be performed in the evaluation of suspected meningitis?
What is the role of serum procalcitonin (PCT) testing in the diagnosis of meningitis?
What does elevated opening pressure in lumbar puncture (LP) and cerebrospinal fluid (CSF) indicate in meningitis?
What does cerebrospinal fluid (CSF) cell count indicate in meningitis?
Why are four tubes of cerebrospinal fluid (CSF) sample drawn in suspected meningitis and where is each sent?
What is the importance of tumor necrosis factor alpha (TNF-?), interleukin (IL)-1, and other cytokines in suspected bacterial
meningitis?
What are the cerebrospinal fluid (CSF) characteristics in acute bacterial meningitis?
What are cerebrospinal fluid (CSF) characteristics in viral meningitis?
What are cerebrospinal fluid (CSF) characteristics in fungal meningitis?
Is fungal serology or cerebrospinal fluid (CSF) culture more commonly used in the workup of fungal meningitis?
Can fungal infection in the blood be used to diagnose fungal meningitis?
What are the cerebrospinal fluid (CSF) characteristics of primary amebic meningoencephalitis (PAM)?
What are the cerebrospinal fluid (CSF) characteristics of Lyme meningitis?
What are the cerebrospinal fluid (CSF) characteristics of tuberculous meningitis?
What is the cerebrospinal fluid (CSF) glucose level in bacterial meningitis?
What is the cerebrospinal fluid (CSF) protein level in bacterial meningitis?
What is the sensitivity and specificity of Gram staining of cerebrospinal fluid (CSF) for bacterial meningitis?
What is the role of acid-fast bacillus (AFB) stain in the diagnosis of meningitis?
How often do cerebrospinal fluid (CSF) bacterial cultures or antigen assays yield the bacterial cause of meningitis?
How effective are cerebrospinal fluid (CSF) culture and antigen testing in the diagnosis of cryptococcal meningitis?
What tests are used to isolate Treponema pallidum (T pallidum) from cerebrospinal fluid (CSF) in syphilitic meningitis?
What is the role of cerebrospinal fluid (CSF) cultures or assays in the diagnosis of Lyme meningitis?
What are the roles of cerebrospinal fluid (CSF) cultures and assays in the diagnosis of tuberculous meningitis?
What is the role of culture from cerebrospinal fluid (CSF) in viral meningitis?
Is neuroimaging (CT scanning, MRI) used in the diagnosis of meningitis?
When is cerebral herniation most likely to occur following lumbar puncture (LP) for meningitis?
What are the IDSA guidelines for screening head CT scanning before lumbar puncture (LP) in adults with suspected
meningitis?
What neuroimaging findings suggest bacterial meningitis?
What central nervous system (CNS) complications of bacterial meningitis are detected on neuroimaging?
Treatment
How is meningitis managed after initial treatment?
What initial steps should be taken to treat suspected meningitis prior to arrival in the emergency department (ED)?
Which tests should be performed first for acute meningitis?
When should antimicrobial therapy be initiated for meningitis?
Which systemic complications of acute bacterial meningitis should be immediately treated?
How are patients monitored for systemic complications of acute bacterial meningitis?
How is hyperventilation managed in intubated patients with meningitis?
When is an intracranial pressure (ICP) monitor indicated in meningitis?
How are seizures managed in meningitis?
How is subacute meningitis treated?
How is bacterial meningitis treated?
What is the prevalence of penicillin resistance among Streptococcus pneumoniae (pneumococcal) strains that cause
meningitis?
Does treatment reduce the risk of mortality in meningitis?
How should patients with bacterial meningitis be monitored during antibiotic treatment?
What is the treatment for bacterial meningitis in the first month of life?
What is the treatment for bacterial meningitis in infants aged 1-3 months?
What is the treatment for bacterial meningitis in children aged 3 months to 7 years?
What is the treatment for bacterial meningitis in children and adults aged 7-50 years?
What antibiotic alternative is available for bacterial meningitis in children and adults aged 7-50 years with severe penicillin
allergy?
What is antibiotic treatment for bacterial meningitis in areas with a low prevalence of drug-resistant Streptococcus
pneumoniae (DRSP)?
What is the role of dexamethasone in the treatment of bacterial meningitis?
What is the antibiotic treatment of choice for patients aged 50 years or older with meningitis?
What are the IDSA guidelines for adjunctive dexamethasone in meningitis?
What is the treatment for bacterial meningitis in the setting of HIV infection?
Is the use of steroid therapy (dexamethasone) effective in the treatment of bacterial meningitis?
What are the benefits of steroid therapy for bacterial meningitis?
Is intrathecal administration of antibiotics FDA approved for the treatment of bacterial meningitis?
How are intrathecal antibiotic dosages determined for bacterial meningitis?
How is viral meningitis treated?
How is herpes simplex (HSV) meningitis treated?

How is cytomegalovirus (CMV) meningitis treated?
What are the causes of fungal meningitis?
How is cryptococcal meningitis treated?
How is intracranial pressure (ICP) reduced in cases of cryptococcal meningitis?
How is HIV-related acute cryptococcal meningitis treated?
What is induction and consolidation therapy for cryptococcal meningitis?
What is the treatment for solid-organ transplant recipients with cryptococcal meningitis?
What is the treatment for meningitis caused by Coccidioides immitis (C immitis)?
What is the treatment for Histoplasma capsulatum (H capsulatum) meningitis?
What is treatment for candidal meningitis?
What is the treatment for Sporothrix schenckii (S schenckii) meningitis?
What is the treatment for tuberculous meningitis?
When is corticosteroid therapy indicated for treatment of tuberculous meningitis?
What is the treatment for syphilitic meningitis?
How is parasitic meningitis treated?
How is Lyme meningitis treated?
How is meningitis prevented?
Which patients should receive the H influenzae type B (Hib) or S pneumoniae vaccines?
What vaccinations are recommended for patients with functional or structural asplenia?
Who should be offered the quadrivalent meningococcal polysaccharide vaccine?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for the use of meningococcal conjugate
vaccines?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for routine use of meningococcal
vaccines in adolescents?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for use of meningococcal vaccines in
individuals with HIV?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for use of meningococcal vaccines in
individuals with persistent complement component deficiency or asplenia?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for persons with increased risk for
exposure to meningitis?
Which meningococcal vaccines for serogroup B are approved by the FDA?
What are the CDC Advisory Committee on Immunization Practices (ACIP) guidelines for routine pneumococcal
vaccinations?
When is chemoprophylaxis for meningitis recommended?
When are consultations with specialists indicated in the treatment of meningitis?
How should meningitis be monitored?
Guidelines
What are the IDSA guidelines on the diagnosis of healthcare-associated ventriculitis and meningitis?
What are the IDSA guidelines on the treatment of healthcare-associated ventriculitis and meningitis?
Medications
When should empiric antibiotic medications be given to treat meningitis?
Which medications in the drug class Sulfonamides are used in the treatment of Meningitis?
Which medications in the drug class Tetracyclines are used in the treatment of Meningitis?
Which medications in the drug class Carbapenems are used in the treatment of Meningitis?
Which medications in the drug class Fluoroquinolones are used in the treatment of Meningitis?
Which medications in the drug class Antibiotics, Miscellaneous are used in the treatment of Meningitis?
Which medications in the drug class Glycopeptides are used in the treatment of Meningitis?
Which medications in the drug class Aminoglycosides are used in the treatment of Meningitis?
Which medications in the drug class Penicillins, Amino are used in the treatment of Meningitis?
Which medications in the drug class Penicillins, Natural are used in the treatment of Meningitis?
Which medications in the drug class Cephalosporins, 3rd Generation are used in the treatment of Meningitis?
Which medications in the drug class Antivirals, CMV are used in the treatment of Meningitis?
Which medications in the drug class Antivirals, Other are used in the treatment of Meningitis?
Which medications in the drug class Antifungals, Systemic are used in the treatment of Meningitis?
Which medications in the drug class Antituberculous Agents are used in the treatment of Meningitis?
Which medications in the drug class Vaccines, Inactivated, Bacterial are used in the treatment of Meningitis?
Which medications in the drug class Corticosteroids are used in the treatment of Meningitis?
Which medications in the drug class Diuretics, Osmotic Agents are used in the treatment of Meningitis?
Which medications in the drug class Diuretics, Loop are used in the treatment of Meningitis?
Which medications in the drug class Anticonvulsants, Hydantoins are used in the treatment of Meningitis?
Which medications in the drug class Anticonvulsants, Barbiturates are used in the treatment of Meningitis?
Which medications in the drug class Anticonvulsants, Other are used in the treatment of Meningitis?
Contributor Information and Disclosures
Author
Rodrigo Hasbun, MD, MPH Associate Professor of Medicine, Section of Infectious Diseases, University of Texas Medical
School at Houston
Disclosure: Received research grant from: Biofire<br/> Speaker for Biofire.
Chief Editor
Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed
Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American
College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America,
Oklahoma State Medical Association, Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.
Acknowledgements
Suur Biliciler, MD Neuromuscular Fellow, Department of Neurology, Baylor College of Medicine
Timothy S Brannan, MD Director, Department of Neurology, Jersey City Medical Center; Professor, Department of
Neurology, Seton Hall School of Graduate Medical Education
Robert Cavaliere, MD Assistant Professor of Neurology, Neurosurgery and Medicine, Ohio State University College of
Medicine
Sidney E Croul, MD Director of Neuropathology, Professor, Department of Pathology and Laboratory Medicine, Medical
College of Pennsylvania Hahnemann University
Francisco de Assis Aquino Gondim, MD, MSc, PhD Associate Professor of Neurology, Department of Neurology and
Psychiatry, St Louis University School of Medicine
Francisco de Assis Aquino Gondim, MD, MSc, PhD is a member of the following medical societies: American Academy of
Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Movement Disorders Society
Alan Greenberg, MD Director, Associate Professor, Department of Internal Medicine, Jersey City Medical Center, Seton Hall
University
Alan Greenberg, MD is a member of the following medical societies: Alpha Omega Alpha and American College of
Physicians
Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American
Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious
Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical
Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria
Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist
Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching
J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine,
University of Virginia School of Medicine
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American
Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Lutfi Incesu, MD Professor, Department of Radiology, Ondokuz Mayis University School of Medicine; Chief, Neuroradiology
and MR Unit, Department of Radiology, Ondokuz Mayis University Hospital, Turkey
Lutfi Incesu, MD is a member of the following medical societies: American Society of Neuroradiology and Radiological
Society of North America
Uma Iyer, MD Resident Physician, Department of Neurology, State University of New York Upstate Medical Center
Pieter R Kark, MD, MA, FAAN, FACP Instructor in Palliative Care, The Lifetime Healthcare Companies
Michael R Keating, MD Associate Professor of Medicine, Chair, Division of Infectious Diseases, Department of Medicine,
Mayo Clinic College of Medicine
Michael R Keating, MD is a member of the following medical societies: American College of Physicians, American Medical
Association, American Society for Microbiology, American Society of Transplantation, Infectious Diseases Society of
America, and International Immunocompromised Host Society
Anil Khosla, MBBS, MD Assistant Professor, Department of Radiology, St Louis University School of Medicine, Veterans
Affairs Medical Center of St Louis
Anil Khosla, MBBS, MD is a member of the following medical societies: American College of Radiology, American Roentgen
Ray Society, American Society of Neuroradiology, North American Spine Society, and Radiological Society of North America
John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for
Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans
Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science,
American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association
of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: MERCK None Other
Marjorie Lazoff, MD Editor-in-Chief, Medical Computing Review
Marjorie Lazoff, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency
Physicians, American Medical Informatics Association, and Society for Academic Emergency Medicine
Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington
University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of
Neurology, Barnes-Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of
Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None
Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine;
Director of Medicine, Elmhurst Hospital Center
Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, Association of Professors of Medicine, and Royal Society of Medicine
C Douglas Phillips, MD Director of Head and Neck Imaging, Division of Neuroradiology, New York Presbyterian Hospital,
Weill Cornell Medical College
C Douglas Phillips, MD is a member of the following medical societies: American College of Radiology, American Medical
Association, American Society of Head and Neck Radiology, American Society of Neuroradiology, Association of University
Radiologists, and Radiological Society of North America
Tarakad S Ramachandran, MBBS, FRCP(C), FACP Professor of Neurology, Clinical Professor of Medicine, Clinical
Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University;
Chair, Department of Neurology, Crouse Irving Memorial Hospital
Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of
Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of
International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart
Association, American Stroke Association, Royal College of Physicians, RoyalCollegeofPhysicians and Surgeons of
Canada, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Abbott Labs None None; Teva Marion None None; Boeringer-Ingelheim Honoraria Speaking and teaching
Raymund R Razonable, MD Consultant, Division of Infectious Diseases, Mayo Clinic of Rochester; Associate Professor of
Medicine, Mayo Clinic College of Medicine
Raymund R Razonable, MD is a member of the following medical societies: American Medical Association, American
Society for Microbiology, Infectious Diseases Society of America, and International Immunocompromised Host Society
Norman C Reynolds Jr, MD Neurologist, Veterans Affairs Medical Center of Milwaukee; Clinical Professor, Medical College
of Wisconsin
Norman C Reynolds Jr, MD is a member of the following medical societies: American Academy of Neurology, Association of
Military Surgeons of the US, Movement Disorders Society, Sigma Xi, and Society for Neuroscience
Robert Stanley Rust Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss
Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child
Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American
Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International
Child Neurology Association, and Society for Pediatric Research
Prem C Shukla, MD Associate Chairman, Associate Professor, Department of Emergency Medicine, University of Arkansas
for Medical Sciences
Manish K Singh, MD Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology
Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain
Management, Jersey Institute of Neuroscience
Manish K Singh, MD is a member of the following medical societies: American Academy of Neurology, American Academy of
Pain Medicine, American Association of Physicians of Indian Origin, American Headache Society, American Medical
Association, and American Society of Regional Anesthesia and Pain Medicine
Niranjan N Singh, MD, DNB Assistant Professor of Neurology, University of Missouri-Columbia School of Medicine
Niranjan N Singh, MD, DNB is a member of the following medical societies: American Academy of Neurology
Mark S Slabinski, MD, FACEP, FAAEM Vice President, EMP Medical Group
Mark S Slabinski, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Ohio
State Medical Association
James G Smirniotopoulos, MD Professor of Radiology, Neurology, and Biomedical Informatics, Program Director, Diagnostic
Imaging Program, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of the
Health Sciences
James G Smirniotopoulos, MD is a member of the following medical societies: American College of Radiology, American
Roentgen Ray Society, American Society of Head and Neck Radiology, American Society of Neuroradiology, American
Society of Pediatric Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Florian P Thomas, MD, MA, PhD, Drmed Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director,
National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor,
Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular
Microbiology and Immunology, St Louis University School of Medicine
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology,
American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, and National
Multiple Sclerosis Society
Frederick M Vincent Sr, MD Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University
Colleges of Human and Osteopathic Medicine
Frederick M Vincent Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic
Examiners, American College of Legal Medicine, American College of Physicians, and Michigan State Medical Society
Amir Vokshoor, MD Staff Neurosurgeon, Department of Neurosurgery, Spine Surgeon, Diagnostic and Interventional Spinal
Care, St John's Health Center
Amir Vokshoor, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of
Neurological Surgeons, American Medical Association, and North American Spine Society
Cordia Wan, MD Adult Neurologist, Kaiser Permanente Hawaii, Kaiser Permanente Southern California
Cordia Wan, MD is a member of the following medical societies: American Academy of Neurology
Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director,
Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency
Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University
Medical Center
Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians,
American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical
Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for
Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society
Lawrence A Zumo, MD Neurologist, Private Practice
Lawrence A Zumo, MD is a member of the following medical societies: American Academy of Neurology, American College
of Physicians, American Medical Association, and Southern Medical Association
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Signs and symptoms

The history should also address the following:

Infants may have the following:

Bulging fontanelle (if euvolemic)

The examination should evaluate the following:

Focal neurologic signs

Signs of meningeal irritation

Systemic and extracranial findings

Cranial nerve palsies

Other focal neurological signs

See Clinical Presentation for more detail.

Early identification and treatment of patients with acute bacterial meningitis

Identifying the causative organism

Blood studies that may be useful include the following:

Complete blood count (CBC) with differential

Blood urea nitrogen (BUN) or creatinine and liver profile

In addition, the following tests may be ordered:

Serum procalcitonin testing

Lumbar puncture and CSF analysis

Neuroimaging (CT of the head or MRI of the brain)

See Workup for more detail.

Initial measures include the following:

Shock or hypotension – Crystalloids

Treatment of bacterial meningitis includes the following:

Steroid (typically, dexamethasone) therapy

In certain patients, consideration of intrathecal antibiotics

The following systemic complications of acute bacterial meningitis must be treated:

Cardiac arrhythmias and ischemia

Exacerbation of chronic diseases

Fungal meningitis - Cryptococcal (amphotericin B, flucytosine, fluconazole), Coccidioides immitis (fluconazole,

Tuberculous meningitis (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin)

Parasitic meningitis (amebic [Naegleria fowleri] or acanthamebic) - Variable regimens

Lyme meningitis (ceftriaxone; alternatively, penicillin G, doxycycline, chloramphenicol)

See Treatment and Medication for more detail.

Dura - A tough outer membrane

Arachnoid - A lacy, weblike middle membrane

Risk factors for meningitis include the following:

Extremes of age (< 5 or >60 years)

Alcoholism and cirrhosis

Recent exposure to others with meningitis, with or without prophylaxis

Contiguous infection (eg, sinusitis)

Dural defect (eg, traumatic, surgical, or congenital)

Intravenous (IV) drug abuse

Malignancy (increased risk of Listeria infection)

Some cranial congenital deformities

Meningitis can also be divided into the following 3 general categories:

Haemophilus influenzae meningitis

Pediatric bacterial meningitis

Preformed tissue planes (eg, posterior fossa)

Temporal bone fractures

The oval or round window membranes of the labyrinths

Obliteration of CSF pathways (causing obstructive hydrocephalus)

Induction of vasculitis and thrombophlebitis (causing local brain ischemia)

Intracranial pressure and cerebral fluid

Cytokines and secondary mediators in bacterial meningitis

Genetic predisposition to inflammatory response

Other viral causes of meningitis include the following: