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Meningitis Treatment &
Management
Updated: Nov 16, 2021
Author: Shikha S Vasudeva, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...

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.
[25]

The patient’s condition and ED organization may warrant 8 to 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 H2O.

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.
[37] 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.
[34,
38] (See tables 7 and 8 below.)

Table 7. Recommended Empiric Antibiotics for Suspected Bacterial Meningitis, According to Age or
Predisposing Factors
[38] (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

Age >50 y
plus 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

Vancomycin plus ceftazidime, cefepime, or meropenem
CSF 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)

Recommended: Penicillin G or
Penicillin MIC ≤0.06 ampicillin
μg/mL Alternatives: Cefotaxime,
ceftriaxone, chloramphenicol

Penicillin MIC ≥0.12

Recommended: Cefotaxime or
μg/mL
Streptococcus ceftriaxone
10-14
pneumoniae Cefotaxime or
Alternatives: Cefepime,
ceftriaxone MIC
meropenem
≥0.12 μg/mL

Recommended: Vancomycin plus

Cefotaxime or cefotaxime or ceftriaxone
ceftriaxone MIC ≥1.0
μg/mL Alternatives: Vancomycin plus
moxifloxacin
Haemophilus Beta- Recommended: Ampicillin 7
influenzae lactamase−negative
Alternatives: Cefotaxime,
ceftriaxone, cefepime,
chloramphenicol, aztreonam, a
fluoroquinolone

Recommended: Cefotaxime or
ceftriaxone
Beta-
lactamase−positive Alternatives: Cefepime,
chloramphenicol, aztreonam, a
fluoroquinolone

Recommended: Meropenem
Beta-
lactamase−negative, Alternatives: Cefepime,
ampicillin-resistant chloramphenicol, aztreonam, a
fluoroquinolone

Recommended: Penicillin G or
ampicillin
Penicillin MIC < 0.1
μg/mL
Alternatives: Cefotaxime,
ceftriaxone, chloramphenicol

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

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

Recommended: Ampicillin or
penicillin G
Streptococcus
... 14-21
agalactiae
Alternatives: Cefotaxime,
ceftriaxone, vancomycin
 Enterobacteriaceae ... Recommended: Cefotaxime or 21
ceftriaxone

Alternatives: Aztreonam, a
fluoroquinolone, TMP-SMX,
meropenem, ampicillin

Recommended: Ceftazidime or
Pseudomonas 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.
[39] 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.
[40]
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%.
[41]

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 to 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 to 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 to 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 to 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.
[42] 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 to 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.
[43]

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.
[44]

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.
[45]

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.
[46]

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.
[47]

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
[47] :

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 four 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.
[48] (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).

Coccidioides immitis
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% to 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.
[49] 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 to 12 months.

[50]

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.
[51]

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 four 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.
[52]

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 to 55 years with certain risk factors for meningococcal
infection.
[53]

Regarding the routine use of vaccines in adolescents, the 2010 CDC-ACIP guidelines specifically
recommend one 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 to 15 years, the
booster can be given at age 16 to 18 years. No booster is needed if the primary dose was given at
age 16 years or later.
[53]
Regarding specific recommendations for individuals with certain risk factors for meningococcal
infection, the ACIP stated that HIV-infected individuals aged 11 to 18 years should be given a
primary series of two 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 to 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.
[53]

Persons aged 2 to 55 years who have persistent complement component deficiency or asplenia
(functional or anatomic) should be given a primary series of two doses, 2 months apart, followed by
a booster dose every 5 years. If a one-dose primary series was given, the booster dose should be
given as soon as possible, then every 5 years thereafter.
[53]

In persons aged 2 to 55 years with a protracted increased risk for exposure to meningitis, the 2010
ACIP guidelines recommend a one-dose primary series. The booster dose should be given after 3
years for children aged 2 to 6 years and after 5 years for persons aged 7 years or older, if the
person remains at increased risk.
[53]

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 three randomized trials conducted in the United States and Europe in
about 2800 adolescents. Among participants who were given three doses of the vaccine, 82%
developed antibodies against four 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.
[54]

In January 2015, a second meningococcal serogroup B vaccine was approved (Bexsero).

[55]

Pneumococcal vaccine

The ACIP recommends administration of 13-valent pneumococcal polysaccharide-protein

conjugate vaccine as part of routine childhood immunization.
[56] The ACIP recommends targeted
use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, formerly PPV23) in children
aged 2 to 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.
[57]

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 for 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
 
 

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