Emergency Neurologic Life Support:

Meningitis and Encephalitis

Katharina M. Busl, MD MS1*†, Jennifer McGuire, MD and

Vikram Dhawan, MD2
1University
of Florida, College of Medicine Departments of Neurology and
Neurosurgery
2Memorial Sloan Kettering Cancer Center Department of Anesthesiology and Critical

Care, New York, NY

Abstract
Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis
(HSE), are severe central nervous system (CNS) infections that, if not treated promptly
and effectively, lead to poor neurological outcome or death.
Because of the impact of early recognition and treatment on outcomes, meningitis
and encephalitis was chosen as one of the Emergency Neurological Life Support (ENLS)
protocols. This protocol provides a practical approach to recognition and urgent treatment
of meningitis and encephalitis.
Appropriate imaging, spinal fluid analysis, and early empiric treatment are discussed.
The typical clinical triad of headache, fever, and neck stiffness, as well as partial man-
ifestations of the triad, should alert the practitioner to the possibility of a CNS infection.
Early attention to airway protection and maintenance of normotension are crucial steps
in the treatment of these patients, as is rapid treatment with antimicrobial agents
and, in some cases, corticosteroids.
This module is meant to give a broad framework for the principles of diagnosis and
management of meningitis and encephalitis, which can be adapted to address global and
regional variations in prevalence and management of these infections based on availability
of diagnostic tools, treatments and local guidelines.
Key words: Meningitis, Bacterial Meningitis, Encephalitis, Herpes simplex encephalitis,
Tuberculous meningitis

*Corresponding author.
†E-mail: Katharina.Busl@neurology.ufl.edu

1
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1 Introduction
Meningitis and encephalitis are potentially life-threatening central nervous system (CNS)
infections, which often present initially to the Emergency Department (ED). Many of
these patients are critically ill and are transported to the ED by Emergency Medical Ser-
vices (EMS). Meningitis is defined as inflammation of the meninges, while encephalitis
is defined as inflammation of the brain. If both are inflamed, the patient has menin-
goencephalitis. Meningitis causes fever, meningismus, and pain (e.g., headache, neck
pain), but, other than depressing a patient’s mental status, does not affect cortical brain
functions (e.g., aphasia, seizure, hemiparesis). Encephalitis typically causes cortical dis-
turbance, particularly altered level of consciousness and seizures. Most patients have a
predominance of meningitis or encephalitis, but many have features of a combined menin-
goencephalitis syndrome. The two CNS infections that are most important to recognize
in the first hour are bacterial meningitis and herpes simplex encephalitis (HSE), as these
diseases produce significant morbidity and mortality and have specific treatments that can
improve patient outcome if administered quickly.
An estimated 500,000 cases of bacterial meningitis occur worldwide each year, of
which more than one-third are fatal. Many survivors are left with neurologic sequelae.1
The incidence and common causative agents have changed considerably in developed
countries since the introduction of conjugate vaccines for Haemophilus influenza B (HiB)
and Meningococcus.2 Because of poverty and poor health care infrastructure, they remain
significantly more common in developing countries.3 The annual incidence of bacterial
meningitis in the U.S. is approximately 3 cases per 100,0001 and the highest incidence
occurs in children under the age of one [76.7/100,000].1 While accurate estimates of
incidence are difficult to obtain, encephalitis is a less common disease than meningitis.
The non-herpes serotypes display seasonal and geographic variation.
Bacterial meningitis and bacterial or viral encephalitis are medical, neurologic, and,
occasionally, neurosurgical emergencies which carry substantial morbidity and mortality
despite modern medical management. According to one study, 48% of patients with bac-
terial meningitis present within 24 hours of the onset of symptoms,4 and hence present a
unique opportunity to start treatment early. Therefore, patients who have a hyper-acute
(hours) to acute (hours to days) onset of headache and altered mental status should be
considered as potentially having meningitis or encephalitis. While children present sim-
ilarly to adults, neonates are more likely to present with non-specific findings including
decreased feeding, irritability, and lethargy.3 Meningitis should be considered in the dif-
ferential diagnosis of any lethargic, vomiting, irritable neonate.
Fever is a major feature of these infectious illnesses. Additional symptoms include
stiff neck or meningismus (typically elicited by neck flexion), new rash, alterations in
mental status, focal neurological findings, or new onset seizures. In a large series of
696 adult patients with bacterial meningitis, the classic triad of fever, neck stiffness, and
change in mental status was present in only 44% of patients, but 95% of patients had at
least two symptoms when a fourth symptom – headache – was added to the classic triad.4
In contrast, another report pooling adult studies of patients with meningitis demonstrated
that 95% of patients had at least two of the three elements of the classic triad.5 The absence
 3

of fever, altered mental status, and neck pain in an immunocompetent patient essentially
eliminates the diagnosis of meningitis and suggests other diagnoses should be pursued.5
A challenge in diagnosing meningitis or encephalitis is that there is no single defini-
tive clinical sign. The exam findings often connected with meningoencephalitis include
Kernig’s and Brudzinsiki’s signs. Kernig’s sign is elicited with the patient lying supine
and passively flexing the hips and knees to 90 degrees. The clinician then extends the
patient’s knee, straightening the leg (i.e., doing a straight leg raise test).5 A positive sign
is present when extension of the leg at the knee produces significant lower back or poste-
rior thigh discomfort due to meningeal irritation. Brudzinski’s sign, in contrast, is elicited
by placing the patient in a supine position and passively flexing the patient’s neck. The
clinician observes whether this action triggers flexion at the hips and knees. Despite
the common teaching of these maneuvers, their sensitivity and specificity for diagnosing
meningitis are unreliable – in a review of literature up to 2018, sensitivity was only 20-
30%, although specificity was high with 85-95%.6 Therefore, the absence of these signs
should not be used to rule out meningitis.7 Another test that has been studied in patients
suspected of having meningitis is the jolt accentuation test. The clinician instructs the
patient to rotate their head horizontally at a frequency of two rotations per second. A
positive jolt accentuation test produces exacerbation of the patient’s headache. In a small
study, this maneuver had a sensitivity of 100% and a specificity of 54% for identification
of meningitis.5

FIGURE 1
ENLS Meningitis and Encephalitis algorithm

The ENLS suggested algorithm for the initial diagnosis and treatment of meningitis
and encephalitis is shown in Figure 1.
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Suggested items to complete within the first hour of evaluating a patient with
menin- gitis and encephalitis are shown in Table 1.

TABLE 1
Meningitis and encephalitis checklist for the first hour

Meningitis and encephalitis checklist for the first hour

 Vital signs, history, examination
 Contact and droplet precautions (until pathogen classified)
 IV access
 Labs: CBC, PT/PTT, chemistries, glucose, blood cultures, lactate

 IV fluids, treat shock

 Immediate administration of dexamethasone followed by appropriate antibiotics
for presumptive bacterial meningitis
 Consider acyclovir (if herpes simplex virus a concern)
 Head CT, if patient neurological exam abnormal
 Lumbar puncture (LP), if CT results available

Management protocol
• Recognize key clinical features of brain infections and identify a possible case of
meningitis or encephalitis
• Establish intravenous access, start initial fluid resuscitation, evaluate airway
• Initiate appropriate treatment based on clinical context
• Perform appropriate diagnostics (lumbar puncture, imaging) without delaying
treatment initiation
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2 Prehospital Considerations
In the prehospital setting, EMS personnel should approach the patient based upon the
chief complaint, assess the basic ABCs of resuscitation (i.e., airway, breathing,
circula- tion), and begin management as appropriate for the severity of the patient’s
presentation and the training level of the EMS providers. This should include
obtaining basic vital signs, formal assessment of mental status utilizing the Glasgow
Coma Score (GCS), mea- surement of serum glucose levels, placement of intravenous
(IV) access, initiation of IV fluid resuscitation, and airway management. If IV access
cannot be rapidly obtained in an unstable patient, placement of an intra-osseous (IO)
cannula should be considered. Pre- hospital resuscitation of patients with life-
threatening infections can expedite achievement of resuscitation goals including
achieving adequate mean arterial pressure (MAP).8 In a population-based
retrospective study, prehospital IV placement and fluid administration were associated
with a decreased likelihood of in-hospital mortality in adult patients who presented
with severe sepsis on admission.9
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3 Initial Assessment in the Emergency Department

As with all acute medical and neurological events, the basic ABCs of resuscitation should
be evaluated immediately on presentation to the ED. Vital signs (including temperature,
blood pressure, heart rate, and respiratory rate, along with peripheral oxygen saturation),
a pain scale, assessment of GCS, and a rapid check of the patient’s serum glucose level
should be obtained at triage and compared to those obtained by prehospital personnel.
In most instances, an oral temperature is adequate. Patients who are markedly tachyp-
neic or shivering may not be able to keep their mouths closed for oral temperature mea-
surement and may require rectal or invasive temperature measurement for accuracy. Both
fever (temperature > 38.0◦C) and hypothermia (temperature < 36.0◦C) are compatible
with CNS infection.
If the patient is normothermic, the pre-test probability of bacterial meningitis or HSE
is decreased. A caveat is if patients have taken antipyretics prior to ED arrival, they
may be afebrile; their temperature should be rechecked during the ED stay. Immuno-
compromised patients, patients with viral meningitis, and even an occasional patient with
bacterial meningitis may present to the ED without fever. In an evaluation of 696 patients
with community-acquired acute bacterial meningitis, the mean reported temperature was
38.8◦C, and 77% of patients were febrile. The evaluation did not report the number of
patients who were hypothermic.4
Immediately after the initial assessment and triage, patients at high risk for meningitis
should be placed on droplet precautions until further workup has been completed. Ad-
equate IV access (i.e., a minimum of two 18 gauge or larger peripheral IVs) should be
placed, and blood samples sent for laboratory analysis, including a peripheral white blood
cell (WBC) count and differential, basic metabolic panel, prothrombin time and partial
thromboplastin time (PT/PTT), serum lactate, and blood cultures. If IV access cannot be
obtained within a few minutes of presentation, IO access should be placed. An initial
fluid bolus of 30 mL/kg of crystalloid solution should be immediately infused over 20 to
30 minutes10 and the patient’s vital signs, mental status, and airway should be reassessed
every five minutes during the initial phase of treatment.
Like patients with other bacterial infections, some patients with bacterial meningitis
will be hypotensive. This may result from sepsis or hypovolemia secondary to increased
insensible fluid losses from fever, tachypnea, diaphoresis, and vomiting. In addition, bac-
terial meningitis, like other diseases causing septic shock, can trigger a pronounced in-
flammatory response, leading to vasodilation, capillary leak, and, in some cases, myocar-
dial dysfunction. The initial resuscitation strategy in critically ill patients with suspected
meningitis or encephalitis that fulfill sepsis criteria should be identical to that recom-
mended for other sepsis and septic shock patients. Surviving Sepsis Campaign recom-
mends beginning resuscitation immediately in patients with hypotension (systolic blood
pressure < 90 mm Hg; MAP < 65mmHg) or a serum lactate of ≥ 4 mmol/L with an ini-
tial fluid challenge of 30 mL/kg of crystalloid over 20 to 30 minutes, in the first 3 hours.
These recommendations are in light of recent randomized trials of alternative resuscitation
strategies in patients with severe sepsis and septic shock suggesting that early identifica-
tion, rapid fluid resuscitation, timely antibiotic administration, and careful monitoring
 7

may be more important than the specific resuscitation algorithm and goals.10−14
One-liter bolus of crystalloid over 20-30 minutes should be given and may be repeated
until the resuscitation goals above are reached or the patient is stabilized, volume replete,
and no longer fluid responsive. The rate of fluid infusion should be reduced to a main-
tenance level once goals are achieved or when the patient demonstrates no further fluid
responsiveness.2,11 Norepinephrine should be used as a first line vasopressor for blood
pressure support if the patient remains hypotensive despite initial resuscitation.
The optimal translation of resuscitation recommendations from sepsis to the man-
agement of patients with CNS infections is unclear, and, in particular, the relationship
between aggressive early volume resuscitation and cerebral edema is yet to be system-
atically investigated. The results of the recently completed ProCESS, ProMISe, and
ARISE studies contribute little to this discussion since fewer than 1% of the patients
enrolled in ProCESS and < 2% of the patients enrolled in ARISE and ProMISe trials had
meningitis.12−17

TABLE 2
Prehospital and ED Considerations
Prehospital and ED Considerations
Early notification (including radio report to prepare and mobilize hospital resources)
Appropriate contact and isolation precautions for transport
Assess airway
Trial of safety of supine position prior to transport Intravenous access with 2 large
bore IV, or IO access.
Adequate fluid resuscitation to maintain hemodynamics
Adherence to guidelines for treatment of sepsis (where appropriate)

4 Diagnostics: CBC and Blood culture

Peripheral WBC can be elevated or depressed in patients with CNS infection, and fre-
quently increased immature forms of WBC’s are seen in peripheral blood.18A normal
WBC count does not rule out meningitis.
Two sets of blood cultures should always be obtained with the initial laboratory draws
prior to initiation of antimicrobial therapy. Among patients with bacterial meningitis, 25-
90% will have positive blood cultures (depending on the causative organism)4,19,20, and
these data will be very helpful in cases where a lumbar puncture (LP) cannot be obtained
in a timely fashion or obtained at all.
The remainder of the diagnostic workup such as neuroimaging and LP should not
delay initiation of empiric antimicrobial therapy. Neuroimaging and LP are discussed
after the section on antimicrobial treatment.
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5 Management
5.1 Initiation of treatment: Start Antibiotics
Appropriate antimicrobials should be started as soon as possible after a patient with sus-
pected CNS infection presents for medical care. In patients with septic shock, each hour
delay in antimicrobial administration after onset of hypotension increases mortality an
average of 7.6%.21 This was confirmed in another study of 261 patients treated with a
protocol-based resuscitation strategy, which showed that mortality nearly doubled from
19.5% to 33.2% when appropriate antimicrobials were delayed by more than one hour
after triage.22
While the applicability of these findings from the sepsis literature to patients with
bacterial meningitis is limited by the small percentage of patients in each study who had
primary CNS infections, less rigorous studies have demonstrated an association between
time to antibiotic administration and outcomes for bacterial meningitis, HSE, fungal CNS
infections and tuberculous (TB) meningitis.23−26 However, delays in antibiotic adminis-
tration are common. In a cohort of 122 patients with documented bacterial meningitis,
one study found a mean time from triage to antibiotics of three hours (interquartile range,
or IQR, 1.6 to 4.3 hours) with 90% of this delay occurring after the initial physician
encounter.24 In a study examining the impact of the 2009 changes in Swedish recommen-
dations for meningitis, the relative increase in mortality was 12.6% per hour of treatment
delay in acute bacterial meningitis after adjusting for all confounding factors.27
The choice of empiric antimicrobials is based on several factors, including the time
course of symptom progression, patient age, and other infectious risk factors. For sus-
pected CNS infections that evolve over hours, bacterial meningitis, viral meningitis, and,
less commonly, viral encephalitis should be considered. In select cases especially of a
more subacute onset over days or weeks, fungal or TB CNS disease should be consid-
ered. Empiric treatment regimens should be chosen to cover all etiologies that the clinical
picture and limited initial diagnostic work-up supports. This may include combinations of
antibacterial, antiviral, and antifungal agents. Local patterns of antimicrobial prevalence
and antibiotic resistance needs to be considered.28
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TABLE 3
Dosing and target pathogens of antimicrobial therapy in adult/pediatric patients with nor-
mal renal and hepatic function.

TARGET AGENT CHILDREN, INFANTS, ADULTS

and TERM NEONATESa
BACTERIAL
Group B Ampicillin 0 to 7 days: 100 mg/kg/dose 2 g IV every 4
Streptococci IV every 8 h h
Listeria 8 to 28 days: 75 mg/kg/dose
Gram-negative IV every 6 h
bacteria (E. coli) > 28 days: 100 mg/kg/dose
IV every 6 h (Maximum
dose: 2 g/dose)
H. influenzae Ceftazidime 0 to 7 days: 50 mg/kg/dose 2 g IV every 8
N. meningitidis IV every 8-12 h h
P. aeruginosa 7-28 days: 50 mg/kg/dose IV
S. pneumoniae every 8 h
≥28 days: 50 mg/kg/dose IV
every 6-8 h (Maximum dose:
6 g/day)
H. influenzae Cefotaxime 0-7 days: 50 mg/kg/dose IV 2 g IV every 4-
N. meningitides every 8-12 h 6h
P. aeruginosa 8-28 days: 50 mg/kg/dose IV
S. pneumoniae every 6-8 h

>28 days: 75 mg/kg/dose IV

every 6-8 h (Maximum
dose: 12 g/day)
H. influenzae Ceftriaxoneb Neonatal: 2 g IV every
N. meningitidis 0-14 days: 50 mg/kg IM once 12h
S. pneumoniae daily
14-28 days: 100 mg/kg X1,
then 80-100 mg/kg/day IM
once daily
>28 days::
80-100 mg/kg/day IV
divided every 12-24 hours
(Maximum dose: 4 g/day)
S. aureus Vancomycin 0-7 days: 10 mg/kg/dose IV 15-20
S. pneumoniae every 8-12 h mg/kg/dose IV
8-28 days: 10 mg/kg/dose IV every 8 -12 h
every 6-8 h
>28 days: 15 mg/kg/dose IV
every 6 h
Enterococcus Gentamicin 0-7 days: 4 mg/kg/dose IV 5 mg/kg/day IV
species every 24 h in divided
Listeria 8-60 days: 5mg/kg/dose IV doses every 8 h
monocytogenes every 24 h
S. agalactiae 60 days - 10 years:
P. aeruginosa 2.5 mg/kg/dose IV every 8 h
≥10 years: 5mg/kg/day IV
divided every 8 h
H. influenzae Meropenem 40 mg/kg/dose IV every 8 h 2 g IV every 8
 10

N. meningitidis (Maximum dose: 2 g/dose) h

S. pneumoniae
Alternative in Aztreonam 0-7 days: 30 mg/kg/dose IV 2 g IV every 6-
penicillin allergy every 8 h 8h
- component of ≥8 days: 30mg/kg/dose IV
empiric therapy every 6 hours (MAX: 8
- H. influenzae g/day)
Enterobacteriacea
e
P. aeruginosa
VIRAL
Herpes simplex Acyclovir 0-90 days: 20 mg/kg/dose IV 10 mg/kg/dose
virus every 8 h IV every 8 h
90 days - 12 years: 10-15
mg/kg/dose IV every 8 h
≥12 years: 10 mg/kg/dose IV
every 8 h (Maximum dose 8
g/day)
Varicella-Zoster Acyclovir Acyclovir dosing: see above 10 mg/kg/dose
virus Or Ganciclovir dosing: see IV every 8 h
below

Ganciclovir
5 mg/kg/dose
IV every 12 h
Cytomegalovirus Ganciclovir 0-3 months: 6 mg/kg/dose 5 mg/kg/dose
(in HIV-infected) every 12 h every 12 h
*off-label ≥3 months: 5 mg/kg/dose Add foscarnet
every 12 h until symptoms
Add foscarnet until improve
symptoms improve
FUNGAL
Candida species Amphotericin <28 days: use conventional Use lipid
Aspergillus B formulation: 1mg/kg/dose IV complex
species once daily formulation: 5
Mucorales ≥28 days: use liposomal mg/kg/dose IV
Mycoses formulation: 5 mg/kg/dose daily
Molds IV once daily (may
Leishmania (may premedicate with premedicate
species acetaminophen + with
Histoplasmosis antihistamine to prevent acetaminophen
Coccidiomycoses infusion reactions) + antihistamine
to prevent
infusion
reactions)
Cryptococcus Liposomal dosing as above. 3-6 mg/kg/day
Empiric in febrile amphotericin IV daily
neutropenic B (may
patients premedicate
with
acetaminophen
+
diphenhydrami
ne to prevent
 11

infusion
reactions)
MYCOBACTER Initial intensive phase
IAL
Empiric for strong Ethambutol Weight-based: ≤40 kg: 15 to
suspicion of <15 years or ≤40 kg: 15 to 25 25 mg/kg/dose
tuberculous mg/kg/dose PO once daily PO once daily
meningitis: (Maximum dose: 1 g/dose) 40-55 kg: 800
combination 40- 55 kg: 800 mg PO once mg PO once
regimen (4 drugs) daily daily
56-75 kg: 1200 mg PO once 56-75 kg: 1200
daily mg PO once
76-90 kg: 1600 mg PO once daily
daily 76-90 kg: 1600
mg PO once
daily

Isoniazid <15 years and ≤40 kg: 10-15 5 mg/kg/dose

mg/kg/dose PO once daily PO once daily
(Maximum dose: 300
mg/dose)
<15 years and >40 kg, or ≥15
years: 5 mg/kg/dose PO once
daily
Pyrazinamide <40 kg: 35 mg/kg/dose PO 40-55 kg: 1000
once daily mg PO once
40-55 kg: 1000 mg PO once daily
daily 56-75kg: 1500
56-75 kg: 1500 mg PO once mg PO once
daily daily
76-90 kg: 2000 mg PO once 76-90kg: 2000
daily mg PO once
daily
Rifampin/rifa <28 days: 2.5-10mg/kg/dose 10 to 20 mg/kg
mpicin IV every 12 h once daily
<15 years and ≤40kg: 10-20 (maximum:
mg/kg/dose IV once daily 600 mg/dose)
<15 years and >40kg, or ≥15
years: 10 mg/kg once daily
(Maximum: 600 mg/dose)
a
Dosing may vary for preterm infants or those with very low birth weight- please
consult local pharmacy formulary
b
Neonates should only receive intramuscular formulations of ceftriaxone. Intravenous
formulations have potential for fatal lung and kidney damage in preterm and term
neonates.
c
In neonates, lipid formulations of amphotericin have poorer penetration into the CNS
than conventional amphotericin, so conventional formulations should be used.
 13
Neonate (<28 days) Infants/Children (≥28 Adults - Adults - Healthcare associated
days) immunocompetent immunocompromised
Ampicillin (0-7 d: 100 Ceftriaxone (80-100 Ceftriaxone (2 g IV Cefepime (2 g IV every Cefepime (2 g IV every 8 h)
mg/kg/dose IV every 8 mg/kg/day IV divided every 12 h) 8 h)
h; 8-28 d: 75 every 12-24 hours;
mg/kg/dose IV every 6 maximum dose: 4 g/day)
h)
Or Or Or Or
°Cefotaxime (75 Cefotaxime (2 g IV Meropenem (2 g IV Ceftazidime (2 g IV every 8 h)
mg/kg/dose IV q6-8h) every 4-6 h) every 8 h)
Plus Plus Plus plus Or
Vancomycin (15 Vancomycin (15-20 Vancomycin (15-20 Meropenem (2 g IV every 8 h)
Gentamicin (0-7 d: 4 mg/kg/dose IV q6h) mg/kg/dose IV every 8- mg/kg IV every 8-12 h)
mg/kg/dose IV every 12 h
24 h; 8-28 d: 5
mg/kg/dose IV every
24 h)
Or Plus (if > 50 yrs) plus Plus
o
Cefotaxime (0-7 d: 50 Ampicillin (2 g IV Ampicillin (2 g IV Vancomycin (15-20 mg/kg IV
mg/kg/dose IV every 8- every 4 h) every 4 h) Q 8-12 h)
12 h; 8-28 d: 50
mg/kg/dose IV every 6-
8 h)
 14
Or
Ceftazidime (0-7 d:
50mg/kg/dose IV every
8-12 h; 7-28 d:
50mg/kg/dose IV every
8 h)
*¶Dexamethasone *¶Dexamethasone
(0.15mg/kg IV q6h) – give (10mg IV every 6 h) –
before or with first dose of give before or with first
antibiotic dose of antibiotic
 14

Notes on Table 4
*in patients with certain risk factors (e.g., unimmunized patients, young children [age
≥6 weeks to ≤5 years], children with sickle cell disease, asplenic patients) or if there
is known or suspected Haemophilus influenzae or S. pneumoniae infection (e.g.,
based on Gram stain results).
¶dexamethasone, if given, should be administered before or immediately after the first
dose of antibiotics. Duration of treatment: 2-4 days for adults and children
◦
Cefotaxime: currently on shortage in U.S.
Vancomycin: not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose
to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL

If Beta lactam allergic:

For Listeria: trimethoprim-sulfamethoxazole - 5mg/kg (based on the trimethoprim
component) IV every 6 to 12h
For S. Pneumoniae, N. Meningitidis, H. influenzae: replace the Beta lactam with
moxifloxacin 400mg po daily or levofloxacin 750mg IV daily
Suspected healthcare associated meningitis: replace Beta lactam with Aztreonam
(2g IV every 6 to 8h) or Ciprofloxacin (400mg IV every 8 to 12h)

5.2 Bacterial Meningitis

Worldwide, Streptococcus pneumoniae and Neisseria meningitides account for the ma-
jority of cases of acute bacterial meningitis. Neonates have a permeable blood brain
barrier and are at risk of infection caused by Group B streptococcus (GBS), Listeria
monocytogenes, and Escherichia coli. Empiric antibiotic therapy should include ampi-
cillin, gentamicin, and a third-generation cephalosporin (ceftazidime or cefotaxime). In-
fants, children, and young adults with bacterial meningitis are at risk for Haemophilus
influenzae (if not vaccinated), Neisseria meningitidis, and Streptococcus pneumoniae.
Middle-aged adults are at highest risk for Streptococcus pneumoniae. As such, both
groups should be started on a third-generation cephalosporin and vancomycin at doses
appropriate for CNS penetration and renal function. The elderly and immunosuppressed
population, including those with alcohol dependence, are at risk for Streptococcus pneu-
moniae and Listeria monocytogenes. As such, they should be started on ampicillin, a
third-generation cephalosporin, and vancomycin at doses appropriate for CNS penetra-
tion and renal function.29 In case of severe penicillin allergy, vancomycin can be used
for gram-positive with moxifloxacin or levofloxacin for S. Pneumoniae, N. Meningitidis,
H. influenzae. Trimethoprim-sulfamethoxazole is used when Listeria is suspected and
aztreonam may be used for Gram-negative coverage.

5.3 Adjunctive Treatment with Steroids

The value of adjunctive treatment with steroids in bacterial meningitis has long been a
topic of debate, and likely, the debate will continue until definitive data are obtained.
There is evidence supporting the use of dexamethasone in bacterial meningitis, particu-
larly in CNS infections caused by Streptococcus pneumoniae.20,30 In a Cochrane system-
atic review and meta-analysis30, it was found that corticosteroids overall reduced the rate
 15

of any hearing loss, severe hearing loss, and neurological sequelae. Subgroup analyses
showed that corticosteroids: (a) prevented hearing loss in children with bacterial meningi-
tis, (b) reduced severe hearing loss only in children with meningitis due to H. influenzae,
(c) reduced mortality in Streptococcus pneumoniae but not for other bacteria, and (d) pro-
tected against severe hearing loss and short-term sequelae for children in high-income
countries, but not for those in low-income countries. This may be due to a higher inci-
dence of malnutrition, delays in seeking treatment, as well as a much higher incidence
of HIV in such countries because advanced HIV disease attenuates host response and
negates any additional benefit of dexamethasone.30
The Infectious Disease Society of America’s (IDSA) practice guidelines from 2004
recommend discontinuation of corticosteroids if it is clearly evident that Streptococcus
pneumoniae is not the cause of the bacterial meningitis.29 However, based on the more
recent data from the above meta-analysis30, the 2016 European Society for Clinical Mi-
crobiology and Infectious Diseases (ESCMID) guidelines on diagnosis and treatment of
acute bacterial meningitis32, dexamethasone should be stopped if the patient is discovered
not to have bacterial meningitis or if the bacterium causing the meningitis is a species
other than H. influenzae or S. pneumoniae, although some experts advise that adjunctive
treatment should be continued irrespective of the causative bacterium. Adjunctive corti-
costeroids are also recommended for TB meningitis regardless of disease severity.25
Dexamethasone is the preferred corticosteroid, when these agents are used, due to
superior penetration into the cerebrospinal fluid (CSF) and a longer half-life.30 Corti-
costeroid should be given 10 to 20 minutes before antibiotics, or with the first dose of
antibiotics until up to 4 hours after the first antibiotic dose.32 Other corticosteroids can
be used in equivalent doses if dexamethasone is not available. There is insufficient data
to recommend starting corticosteroids in neonates.29,32 A recent study evaluating delayed
outcomes after treatment for bacterial meningitis in adults found that adverse clinical out-
come was associated with the use of adjunctive steroids.33 The overall implication of this
recent report is yet to be seen.

5.4 Neuroimaging in Suspected CNS Infection

In a patient with suspected CNS infection, performance of head CT and LP should not
delay antimicrobial treatment. Emergent imaging, especially in the first hour of presen-
tation with a suspected CNS infection, usually starts with a CT scan of the head. In a
study of the need for head CT prior to LP among 301 patients with suspected bacterial
meningitis, 78% of patients had a head CT performed prior to LP.34 Of these patients,
24% had an abnormality on the CT, and 5% had evidence of mass effect. Age > 60 years,
immunocompromised state, history of CNS disease, altered level of consciousness and
focal neurologic deficits were predictive of abnormal CT findings. If CT scans were or-
dered only on those individuals with a predictive sign of CT abnormality, the rate of CT
acquisition would have decreased by 41%.34 The IDSA Practice Guidelines for the Man-
agement of Bacterial Meningitis29,35−37, recommend that head CT should be done prior
to LP if certain features are present at baseline as they are likely to be associated with
abnormal findings on a head CT (see box below).
 16

Indications for neuroimaging prior to Lumbar Puncture

 Patient is ≥ 60 years
 History of CNS disease
 Immunocompromised state
 History of seizure (within one week of presentation)
 Abnormal neurologic exam findings
 Impaired level of consciousness
 Abnormal language
 Cranial nerve findings
 Motor findings
 Papilledema or loss of venous pulsations on fundoscopic examination

Brain herniation after LP occurs in approximately 5% of cases or less.36 CT scan can

detect brain shift and findings of impending herniation, contraindicating an LP. However,
CSF pressure may be elevated, even to levels where herniation may occur, in absence of
abnormalities on CT.35,36 Meningitis can be fulminant and characterized by progressive
inflammation of the meninges and brain swelling. Patients can herniate after LP because
of disease progression, or due to the inflammatory response to bacterial proinflammatory
substances liberated after antibiotic administration (especially if steroids are not given
around the time of first antibiotic administration), and not necessarily as a result of the
LP.35,36 Vice versa, CSF pressure can be normal in patients with space occupying lesions
causing brain shift seen on CT scan, even in the stage of herniation, and the LP may lead
to herniation even with the CSF having normal pressure.35,36 Because of these findings,
it has been suggested that the terms “raised intracranial pressure (ICP)” and “intracra-
nial hypertension” are ambiguous and should be avoided. Instead, it should be specified
whether brain shift, raised CSF pressure, or a combination of the two is present.35 Ongo-
ing leakage of CSF after LP has been suggested to be responsible for delayed herniation
several hours later (up to 12 hours in one report).36
Glimaker et al37 reported on data showing that moderately to severely impaired con-
sciousness alone, in the absence of focal neurological signs or other findings indicating
a space-occupying lesion or signs of imminent herniation is not a contraindication to LP
without head CT scan. In addition, new onset seizures (if not ongoing), and immuno-
compromised state did not appear to be contraindications for LP before CT scan in the
data reviewed, as long as in both there were no focal neurological signs or other findings
indicating a space-occupying lesion or signs of imminent herniation. These data resulted
in a revision of the Swedish guidelines on acute bacterial meningitis in 2009, in which
new onset seizures and immunocompromised state as contraindications to initial LP be-
fore head CT scan were removed.27,37 Of note, the IDSA guidelines on meningitis were
last updated in 2004, without availability of a similar recent update.29
Importantly: obtaining a cranial CT and performing an LP should never delay an-
tibiotic administration and initial resuscitation. With the most sensitive organisms, CSF
sterilization occurs only after 4–6 hours following initiation of antimicrobials.19
In patients who do not present with above-mentioned signs, have normal mental sta-
tus, and have no focal neurologic deficits, a head CT is not always required prior to LP.
 17

However, in most patients who have a clinical presentation consistent with acute bacterial
meningitis or encephalitis, there will be enough diagnostic uncertainty that CT may be
advisable prior to LP to rule out other etiologies.
An LP is helpful in a patient without classic symptoms but suspicion for CNS infec-
tion, as it also serves the evaluation of encephalitis.
Known or suspected immunocompromised patients may present with less classic signs
of meningitis or encephalitis. For such patients, the clinician should lower the pre-test
probability for these diagnoses and err on the side of a more complete work-up, including
emergent brain imaging followed by LP as above.
In cases of a normal head CT in the presence of fever, abnormal WBC, headache, and
altered mental status, suspicion for meningitis or encephalitis should remain moderate
to high. If the head CT shows a condition that adequately explains the patient’s clini-
cal presentation, the evaluation of bacterial meningitis can be aborted or adjusted to the
diagnostic findings.

FIGURE 2
Axial CT in a 64-year-old man presenting with headache, altered mental status and
fever. The CT shows multiple hypodense lesions (yellow arrows) with sur- rounding
edema (white arrows) bilaterally in the parasagittal frontal lobes and right temporal
lobe. He was, on further work-up with magnetic resonance imaging (MRI) of the brain,
diagnosed to have multiple brain abscesses.

6 LP and CSF Analysis

Lumbar Puncture to obtain CSF for analysis is essential for both establishing a diagnosis
and tailoring therapy. Potential contraindications should be considered including a space
occupying lesion with mass effect, abnormal intracranial pressure, local infection at the
puncture site and increased bleeding risk that may include the use of anticoagulant med-
ications, coagulopathies, and thrombocytopenia. Informed consent should be obtained
 18

prior to obtaining CSF via LP, when possible, and the clinical team should perform a
“time-out” prior to starting the procedure.
Optimally the patient should be positioned in the left lateral decubitus position, as
an opening pressure (OP) cannot be measured if the patient is sitting up. After prepping
and draping the patient in the usual, sterile fashion, and accessing the subarachnoid space
with a spinal needle, the OP should be measured with a manometer prior to the collection
of CSF. An elevated OP is indicative of elevated ICP. If the OP is found to be greatly
elevated expert opinion recommends that the needle stylet should be left in place and
mannitol administered. It may be prudent to recheck the pressure after a few minutes to
confirm that the CSF pressure has declined, before removing the needle. To avoid CSF
leakage and post LP headache, the patient should keep the head of bed less than 15 degrees
following the procedure for 30 minutes.
CSF should be collected in a minimum of four tubes (Table 5). CSF should be sent
for cell count and differential, protein, glucose, lactic acid (if available), gram stain and
cultures, and specific testing for pathogens as indicated (Table 5). Newer technologies
such as multiplex polymerase chain reaction (PCR), proteomics and genetic sequencing
may be available and provide a faster and more accurate diagnosis for bacterial meningitis
compared to culture.28
Larger volumes of CSF increase the sensitivity of a Gram’s stain and culture and is
also helpful for culture when there is a suspicion of TB or fungal meningitis. Clinicians
should be aware of local laboratory policies regarding minimum amounts of CSF required
for Gram’s stain and culture.
TABLE 5
Tubes for collection of CSF
Tub Tes
Always measure an opening pressure before collecting CSF. CSF entering the
manometer can then be emptied into Tube 1 and used for cell count and differential.
1 (and 4) Cell count and differential (if tube 1 was turbid or bloody, and
tube 4 is clear, this suggests a traumatic tap)
2 • Protein
• Glucose
• Lactic acid
• Consider: procalcitonin
3 • Gram stain and cultures
• CSF herpes simplex virus and enterovirus PCR (may also
send in tube 2)
• Save our specimen*
4 (and 1) Cell count and differential
* The save our specimen sample may be used later for additional studies as indicated by
clinical scenario and preliminary CSF cell counts and chemistries. Additional studies
may include (though are not limited to): additional PCR testing, specific pathogen-
directed antigen and antibody assays, India ink stain (if fungal infection is suspected),
viral and/or fungal cultures.
 TABLE 6
CSF Analysis
LP findings in WBC RBC CSF glu- CSF protein Organisms Opening pressure
meningitis cose/serum
glucose ratio**
Normal* [56-58] Neonates 0- Absent > 0.6 Neonates 0-28days: None Children: 11.5-
28days: 0- <127mg/dL 28cmH2O
15cells/µL Infants 29-56days: Adults: 6-25
Infants 29- < 99mg/dL cmH2O
56 days: 0-9 Children >56days and
cells/µL adults: <50mg/dL
Children >56
days and adults:
0-5 cells/µL
Bacterial 100s to 1,000s Usually < 0.6 elevated Seen on Gram’s 20-50 cmH2O
cells/µL, neu- normal stain in approx-
trophil predomi- imately 70% of
nance cases
Continued on next page

19
 Table 6 continued
Non-Herpes 10 to several Absent Slightly de- < 50mg/dL usually. If Absent on the 6-30cmH2O
Virus 100cells/µL, creased or elevated, it is usually Gram’s stain
lymphocyte normal <100mg/dL Despite these
predominance characteristics,
continue antibi-
otics until CSF
culture results are
negative and clin-
ical improvement
is demonstrated.
Continued on next page

20
 Table 6 continued
Herpes virus 100scells/µL typ- 10–100cells/ µ > 0.6 Either < 50mg/dL or Absent on the 6-30cmH2O
ically with a lym- or higher mildly elevated, usually Gram’s stain
phocytic predom- <100mg/dL The presence
inance of seizures and
findings of uni-
or bilateral hy-
podensities with
or without hem-
orrhage in the
frontal or tempo-
ral lobes on brain
MRI, and rarely
on brain CT
scans, are also
compatible with
this diagnosis.
Fungal May be normal Absent Decreased or >50mg/dL, often highly India ink stain 20-100cmH2O
or normal elevated can detect Cryp-
If elevated it tococcus
is usually 100
to 400cells/µL,
lymphocyte
predominance
Continued on next page

21
 Table 6 continued
Tuberculosis Elevated, usu- Absent < 0.6 > 50mg/dL, often highly Acid fast bacilli 20-40cmH2O
ally 100 to elevated occasionally
400cells/µL, seen on smear
with lymphocyte with Kinyoun or
predominance Ziehl-Neelsen
stains
* Neonatalranges provided are for term neonates with normal birth weight. Values may varyfor preterm or low birth weight neonates.
** Anabsolute normal range cannot be given for CSF glucose; it is usually consideredto be normal when the CSF glucose/serum glucose ratio is > 0.6 . The CSF glucose levels generally
do not riseabove 300mg/dl (16.7 mmol/L) regardless of serum levels, so the ratio maydecrease with rising serum glucose level. In neonates the CSF/serum glucose ratiovaries more than
adults and is generally higher in normal CSF [37]. Overall, elevatedglucose level in the CSF only occurs with hyperglycemia, and not with any otherCNS pathologies.

22
 23

In patients with CSF findings suggesting bacterial meningitis, clinicians should con-
tinue antibiotics, stop acyclovir, and continue dexamethasone. Subsequently, they should
adjust antibiotics, and either continue or stop dexamethasone based on final culture results
and sensitivities.
In addition to antibiotics and dexamethasone, supportive care and management of
other organ systems is important in patients with bacterial meningitis. Some patients
may have a concomitant bacteremia with the offending pathogen and may require fo-
cused resuscitation and management of sepsis. If the LP demonstrates an elevated OP,
ICP monitoring, and treatment of intracranial hypertension may be required. Details of
management of intracranial hypertension can be found in the ENLS manuscript on the
same topic and in the 2020 Neurocritical Care Society Guidelines for Cerebral Edema
Management.

6.1 Prophylaxis
Close contacts of patients diagnosed with meningococcal infection are defined as those
who have had > 8 hours of contact while in close proximity of < 1 meter or have been di-
rectly exposed to oral secretions within 7 days prior to onset of symptoms or until 24 hours
after initiation of antimicrobials. For these close contacts, chemoprophylaxis should be
administered as early as possible, i.e., within 24 hours. Regimens for adults include either
rifampin 600 mg orally every 12 h for two days, a single oral dose of ciprofloxacin 500
mg or single dose of intramuscular ceftriaxone 150 mg. Vaccination with meningococ-
cal vaccine to boost herd immunity and promote outbreak control is recommended when
there is a meningococcal outbreak.

6.2 Encephalitis
Encephalitis is defined by the presence of an inflammatory process of the brain in associ-
ation with clinical evidence of neurologic dysfunction. Most of the pathogens that cause
encephalitis are viruses. However, other pathogens such as bacteria, Mycobacteria (TB),
spirochetes, Rickettsia, Ehrlichia, fungi, and protozoa can also cause encephalitis.
Despite extensive testing, the etiology of encephalitis remains unknown in most
patients.39 In patients with encephalitis, it may be difficult to determine the relevance of
an infectious agent identified outside of the CNS (e.g., from blood, stool, nasopharynx,
or sputum), which may play a role in the neurologic manifestations of illness, but not
necessarily by directly invading the CNS.39 Symptoms and signs of encephalitis and
meningitis are similar, for example, decreased level of consciousness may be present
in meningitis due to inflammation of the brain tissue, but not necessarily due to direct
infection of the brain tissue. Noninfectious CNS diseases (e.g., vasculitis, collagen
vascular disorders, autoimmune and paraneoplastic syndromes) may present in a similar
way to infectious causes of encephalitis and should be considered in the differential
diagnosis. Many cases of encephalitis do not have definitive treatment, but specific
agents should be sought and identified, when possible, which is important for prognosis,
potential prophylaxis, and counseling of patients and family members, as well as public
health interventions.
 24

Diagnosis of encephalitis requires an LP, which may need to be delayed if the previ-
ously mentioned contraindications are present. If encephalitis is being considered in the
differential diagnosis of CNS infection, then an MRI of the brain should be done within
24 to 48 hours after admission, as it is the most sensitive neuroimaging test to evaluate
patients with encephalitis. If MRI cannot be done, then CT with and without contrast
enhancement can be done instead.39 If the MRI is being performed before the LP, the
initiation of appropriate antimicrobials should never be delayed until the imaging is done.
Detection of IgM antibodies in CSF caused by numerous viruses is diagnostic of neuroin-
vasive disease. Cultures of the CSF are of limited value in determination of viral causes
but are helpful in diagnosing bacterial and fungal infections. The PCR test greatly in-
creases the ability to diagnose infections of the CNS, especially viral infections caused by
Herpes viruses, including Herpes simplex, and should be done on all patients suspected
of having meningitis/encephalitis. If a patient with encephalitis has a negative PCR, and
continues to display symptoms despite adequate treatment, consideration should be given
to repeating the test after 3 to 7 days, as the PCR can be false negative very early in the
disease. Despite a wide range of viruses that can cause encephalitis, specific antiviral
therapy is generally limited to Herpes viruses (especially Herpes simplex virus) and HIV,
treated with acyclovir and antiretrovirals, respectively.39

F IGURE 3

CT and MRI Brain of herpes encephalitis 75-year-oldmale presenting with two days of
altered mental status, low grade fever and seizure. Panel A: CT scan of head shows
extensive edema involving the right medial temporal lobe with hemorrhagic conversion.
Panel B: MRI brain (FLAIR sequence) shows extensive vasogenic edema involving the
right medial temporal and right medial orbitofrontal lobes suggestive of herpes
encephalitis.

For suspicion of viral encephalitis and, particularly, HSE, treatment should begin with
IV acyclovir. Acyclovir needs to be adjusted in cases of impaired renal function. Hydra-
tion should be sufficient to achieve normovolemia, thereby avoiding the complication of
acyclovir-associated renal failure. For varicella-zoster virus (VZV), acyclovir is recom-
 25

mended, but ganciclovir can be given alternatively. For cytomegalovirus, the combination
of ganciclovir and foscarnet is recommended (see Table 3).
The treatment of non-herpetic viral encephalitis is primarily supportive in nature.
Many of these patients will have a significantly depressed level of consciousness, mak-
ing close observation and airway management crucial. For West Nile virus, there is risk
of respiratory decompensation from neuromuscular weakness secondary to spinal cord
involvement and depression of consciousness. Oxygen saturation may fall due to aspi-
ration or hypoventilation and CO2 may rise as an early indicator of ventilatory failure.
Admission to the ICU for observation is frequently warranted.
Other forms of viral encephalitis, such as those caused by the arboviruses, including
West Nile virus, may also have a sub-acute presentation.40 There are no pharmacothera-
peutic interventions for these encephalitides, but until exclusion of HSE can be verified,
empiric acyclovir is reasonable.

6.3 Mycobacterial CNS Infection

TB meningitis is another CNS infection to be considered in the early differential diagno-
sis, especially if there has been a subacute and more protracted course of onset of illness.
In a patient presenting with a symptom duration of more than 5 days, particularly if the
patient is immunocompromised, the diagnosis of TB meningitis should be considered.41
Tuberculosis is more prevalent in high-risk groups including the homeless, nursing home
residents, ethnic minorities, and persons infected with HIV.42 Cranial nerves are affected
in 20% to 30%, most commonly III, VI, VII, and VIII.43 TB meningitis can be compli-
cated by hydrocephalus, tuberculomata, brain abscess formation, and disorders of sodium
and water metabolism.44 Demonstration of acid-fast bacilli in the CSF is the gold standard
of diagnosis. However, sensitivities vary with technique and are at best 60%, and results
take 2 to 6 weeks of incubation.44 Therefore, in practice, a combination of clinical presen-
tation, CSF appearance, imaging, and acid-fast bacilli at other sites is used to make a pro-
visional diagnosis. CSF OP is usually moderately elevated (18-30 cm H2O), CSF glucose
is often depressed (< 2.2 mmol/L), and CSF protein is usually elevated.42 Acellular CSF
profiles may occur.45 PCR assays have improved the diagnostic process in TB meningitis
with sensitivity of 56-76% and specificity of 89-98%, depending on the assay.46,47 Imag-
ing may reveal hydrocephalus, tuberculomata, or meningeal enhancement, seen best with
MRI, as 25% of head CT scans performed at the time of initial presentation are normal.43
Empiric treatment regimens are largely based on those for pulmonary TB, with a
staged combination regimen (see Table 3). Treatment delay is to be avoided like any
other bacterial meningitis.48

6.4 Fungal Meningitis or Encephalitis

Fungal CNS infections are highly variable in clinical presentation and need to be consid-
ered in suspected CNS infections that evolve over days in an immunosuppressed patient.
Prior history of CNS disease or systemic fungal infections and rapid disease progression
should raise the index of suspicion for fungal meningitis.
 26

As with other CNS infections, fast identification and treatment initiation significantly
affects the odds of a better outcome.26 Typical CSF findings include lymphocytic pleocy-
tosis (few to several hundred per HPF) and for certain organisms also with eosinophilic
predominance. CSF glucose is decreased, and CSF protein is generally elevated (up to
13.9 mmol/L or beyond). If CSF acquisition via LP is difficult or impossible, it can be
an indicator of very high (>1gm/dL) CSF protein and obstructive hydrocephalus. Empiric
amphotericin B should be administered during diagnostic testing.

7 Pediatric Considerations
Bacterial meningitis is an important contributor to pediatric morbidity and mortality.49
Diagnosis can be difficult in infants who often have non-specific manifestations such as
fever, hypothermia, lethargy, irritability, respiratory distress, poor feeding, vomiting, or
seizures. In older children, clinical manifestations include fever, headache, photopho-
bia, nausea, vomiting, and decreased mental status.50 The major pathogens involved are
dependent on the age of the child29,49:

• Neonatal period: depending on early (within the first week of life) versus late onset
(between the second and sixth weeks of life); most common pathogens GBS, E.
coli, other gram-negative bacilli51
• <2 months: GBS, Listeria monocytogenes, Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae
• 2 to 23 months: Streptococcus pneumoniae, GBS, N. Meningitidis, Haemophilus
influenzae29,52

• 2 to 10 years: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus

influenzae
• 11 to 17 years: Neisseria meningitidis, Streptococcus pneumoniae

Bacterial meningitis is a true pediatric medical emergency and immediate diagnostic and
therapeutic steps must be taken (Figure 4). The initial management should include eval-
uation and restoration of normal oxygenation, ventilation, and perfusion. For children
with a GCS ≤ 8 and/or lack of airway protective reflexes, intubation for airway protec-
tion is advised. Like adults, pediatric patients with bacterial meningitis may also present
with signs and symptoms of septic shock. Per the Pediatric Septic Shock Guidelines29,52
IV access with rapid isotonic fluid resuscitation of 20-60 mL/kg in the first hour should
be administered with a goal to restore normal peripheral perfusion, heart rate and blood
pressure for age. If shock is fluid refractory, epinephrine for cold shock or norepinephrine
for warm shock should be initiated. Supportive care should also include detection and
management of hypoglycemia, acidosis, and coagulopathy.
LP and blood cultures should be performed without delay, and empiric antibiotics
should be given immediately following its completion. If performance of blood cultures
 27

FIGURE 4
Approach to suspected CNS infection in infants and children
 28

or the LP is not possible or must be delayed (i.e., due to the need to obtain brain imag-
ing), initiation of antibiotic therapy should not be postponed. Children with mass effect
on brain imaging or sings of intracranial hypertension are at higher risk of cerebral her-
niation when a LP is performed. If signs of mass effect or intracranial hypertension are
evident on neuroimaging (prior to LP), or the LP has an elevated OP, neurosurgery should
be consulted for ICP monitoring. There is some evidence to support that aggressive man-
agement of cerebral perfusion pressure improves outcome in pediatric patients with acute
CNS infections.29
An empiric antibiotic regimen (Table 4) for infants < 2 months of age should include
ampicillin, gentamicin, and cefotaxime.29 In older infants, children, and adolescents, the
appropriate empiric treatment regimen should cover penicillin resistant S. pneumoniae
and N. meningitidis.52 Pneumococcus is the most common cause of bacterial meningitis
in pediatric patients from ages 2 months to 11 years. Therefore, it is important to consider
in-vitro susceptibility for Pneumococcus. In case of penicillin allergy, alternatives such
as aztreonam or levofloxacin (depending on the organism targeted) should be considered.
The empiric antibiotic regimen should be broadened in infants and children with immune
deficiency, penetrating head trauma, other anatomic defects, or if the development of
meningitis is healthcare-related.53 The recommended empiric therapy for these patients
is vancomycin plus an antipseudomonal beta-lactam (such as cefepime, ceftazidime, or
meropenem), per the practice guidelines of the IDSA.53
Adjunctive therapy with dexamethasone has been discussed previously. The Ameri-
can Academy of Pediatrics Committee on Infectious Diseases suggests that dexametha-
sone therapy may be beneficial in children with Hib meningitis if given before or at the
same time as the first dose of antimicrobial therapy and that it should be considered for
infants and children with pneumococcal meningitis after weighing the potential risks and
benefits.54 The 2016 ESCMID guidelines32 state that based on expert consensus, dexam-
ethasone can still be started up to 4 hours after initiation of antibiotic treatment. Finally,
there is insufficient data to recommend starting corticosteroids in neonates.29,30,32
Children with encephalitis present with symptoms of CNS dysfunction including al-
terations of consciousness, cortical dysfunction with focal neurologic signs and ataxia.
Additional signs and symptoms include fever, seizures, and abnormal neuroimaging.55 As
in the case of children with bacterial meningitis, the initial management includes restora-
tion of normal oxygenation, ventilation, and perfusion, as well as detection and manage-
ment of hypoglycemia, acidosis, and coagulopathy. Seizure detection and treatment are
also vital.
Acute flaccid myelitis (AFM) has emerged as a rare but feared problem where previ-
ously healthy children present with acute paralysis.52 While encephalitis from enterovirus
is relatively well known, there is emerging evidence that AFM may be a delayed response
to respiratory enterovirus infection, particularly Enterovirus D68. Typically, children have
a viral respiratory or, less commonly, gastrointestinal prodrome with fever, headache,
neck stiffness and myalgia in varying combinations. This is followed by a rapidly pro-
gressive flaccid limb weakness over hours to days (upper limbs, respiratory or quadri-
paresis) +/- cranial nerve and bowel/bladder involvement. CSF shows pleocytosis and
elevated protein, but no virus has been isolated in the CSF. MRI of the spinal cord shows
 29

longitudinally extensive predominantly gray matter involvement. Treatment is supportive

including respiratory support.
Finally, several infectious diseases previously thought to be eradicated by immuniza-
tions have been increasingly observed due to declining rates of vaccine use in certain
areas. Post infectious measles encephalitis and mumps-associated meningitis, which can
complicate up to 10% of mumps cases, are some examples. Mumps-associated meningitis
is generally benign, although long term sequelae from encephalitis are common.

8 Nursing Considerations
The role of the nurse for a patient who presents with suspected meningitis includes assist-
ing the providers with the initial examination, airway, and hemodynamic stabilization, ob-
taining intravenous access, and prompt administration of antibiotics. Nursing assessment
should include establishing an initial neurologic exam and baseline vital signs. Respira-
tory status can be compromised due to a declining level of alertness or from concomitant
pneumonia. Close monitoring of respiratory status including respiratory rate, ability to
clear secretions, pattern, and depth of respiration, etc. is important in identifying patients
who need endotracheal intubation. Hemodynamic compromise can occur in patients with
meningitis including sepsis and/or septic shock. The bedside nurse should closely monitor
the patient’s volume status and hemodynamics paying particular attention to blood pres-
sure and heart rate trends. Hyperthermia can occur secondary to infection.56 Antipyretics
and other measures of fever control should be instituted promptly and as needed. Vigilant
monitoring for complications of meningitis and encephalitis including signs or symp-
toms of cerebral edema (e.g., Cushing’s triad), increased ICP, hydrocephalus and seizures
with prompt notification to provider teams with any change in status. Additionally, the
nurse should anticipate regular monitoring of labs, with particular attention towards the
metabolic panel to trend serum sodium as well as changes in creatinine related to the ad-
ministration of antimicrobials. Seizure precautions should be in place for all patients with
meningitis and encephalitis including keeping the bed in low position with padded side
rails and suction and oral airway available at bedside.56 Finally, nurses should be vigilant
about enforcing droplet and isolation precautions to minimize spread of infection.

9 Communication
Transfer of care to the accepting health care team is an important step to maintain continu-
ity of management. Most patients with bacterial meningitis and viral encephalitis require
the oversight and care that an ICU can provide. Tables 7 and 8 outline information that is
important to pass along to the accepting health care team.
 30

TABLE 7
Meningitis and encephalitis Communication checklist
Communication sign out
 Presenting signs, symptoms, vital signs on admission and relevant past medical
history
 Relevant laboratory results including white blood cell count, bicarbonate level,
lactate level, and renal function
 Head CT and results if obtained
 IV fluid administered, input/output
 Antibiotics administered and time started; dexamethasone if given
 Results of LP, including opening pressure
 Current vital signs, pre-transfer physical and neurological exam
 Ongoing concerns, active issues, outstanding studies/tests
 Infectious precautions applied/required

TABLE 8
Sample Structured Communication
Communication – elements to include
 Age
 GCS
 Airway status
 Hemodynamic condition
 Presumed pathogen (bacterial, viral etc.)
 Imaging findings
 Antibiotics, steroids
 Precautions necessary

Communication – structure and sample

Prehospital provider to ED: “This is Medic 2 calling for a destination request for a
24-year-old male with fever, headache, vomiting and altered mental status. Concern
for bacterial meningitis, droplet precautions in place. On arrival at the patient’s home,
he was agitated but alert. 8 minutes into the transport, he vomited and now is
progressively lethargic. We are assisting oxygenation with a nasal cannula. On alert
for intubation if further vomiting and decline in mental status. Blood pressure is
100/60 mm Hg, tachycardic at 110 with a temperature of 38.3 degrees celsius. He has
received one liter of normal saline and has one peripheral antecubital 18 g IV."

ED handoff to ICU: "24-year-old male, with purulent discharge from right ear,
ruptured tympanic membrane, fever of 101 F, headache and progressive altered
mental status, GCS 8 (E2 M4 V2), meningismus. Intubated in ED in one attempt with
a size 6.5 ETT, concern for bacterial meningitis, on droplet precautions. CT scan
normal; LP with opening pressure 18, 5400 WBC, neutrophils 90%, protein 120,
glucose 50. CSF gram stain pending. Blood cultures sent. Vancomycin, cefepime and
dexamethasone 8 mg given. 2 lit NS given, BP 110/65 mm Hg."
 31

Clinical Pearls
 95% of patients with meningitis have 2 of the following: fever, neck stiffness/pain,
change in mental status and headache.
 Encephalitis results in depressed mental status and affects cortical brain function
(e.g., aphasia, hemiparesis).
 A high index of suspicion is required for immunocompromised patients and
neonates as they can present with atypical symptoms and unusual pathogens like
fungi and TB.
 Bacterial meningitis and Herpes encephalitis have specific treatments that can
improve patient outcome if administered quickly.
 Two sets of blood cultures should be obtained prior to antibiotics.
 A normal WBC count in the peripheral blood does not rule out meningitis.
 Certain clinical signs can be predictive of an abnormal head CT; a head CT should
be obtained when these are present prior to performing an LP.
 Herniation can occur in up to 5% of patients, when LP is done, even with a normal
head CT
 Lumbar puncture is essential for diagnosis. However, performance of CT and LP
should not delay antimicrobial treatment.
 Ceftriaxone, Vancomycin, and Acyclovir should be started empirically for bacterial
meningitis. For adults > 50 years, immunocompromised patients, or infants <2
months old, Ampicillin should be added to cover Listeria.
 Dexamethasone should be started 10-20 minutes before, with or up to 4 hours after
antibiotics for bacterial meningitis. Further continuation of steroids depends on the
specific bacteria identified.

10 Starred References
#29, Tunkel, A.R., et al: 2004 IDSA guidelines on acute community acquired meningitis-
one of the most comprehensive sources of information on acute bacterial meningitis
#30, Brouwer, M.C., et al: The basis for the ESCMID recommending steroids not
only for Streptococcus pneumonia, as stated in the 2004 IDSA guidelines, but also for
Haemophilus influenzae.
#32, van de Beek, D., et al: The ESCMID guidelines from 2016- it is the most recent
guideline for acute bacterial meningitis.
#34, Hasbun, R., et al: Describes the clinical findings predictive of an abnormal head
CT that would preclude an LP.
#39: Tunkel, A.R., et al: IDSA encephalitis guidelines- one of the most comprehensive
sources of information on encephalitis.

11 References
1. van de Beek, D., de Gans, J., Tunkel, A.R.Wijdicks, E.F. Community-acquired bacterial
meningitis in adults. N Engl J Med 2006;354(1):44-53.
2. Schuchat, A., Robinson, K., Wenger, J.D., et al. Bacterial meningitis in the United
States in 1995. Active Surveillance Team. N Engl J Med 1997;337(14):970-6.
 32

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Acknowledgements
The authors are grateful for the contributions and insight provided by the following re-
viewers: Natalie Gofman, Pharm.D., BCPS, BCCCP; Yasser Abulhasan, MBChB, FR-
CPC, FNCS.