Neurocrit Care

https://doi.org/10.1007/s12028-019-00816-2

MENINGITIS AND ENCEPHALITIS

Emergency Neurologic Life Support:

Meningitis and Encephalitis
Katharina M. Busl1*, Ricardo Hernandez2, William J. Meurer3, Sarah Peacock4 and Sandra D. W. Buttram5,6

© 2019 Neurocritical Care Society

Abstract 
Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis, 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 were chosen as one of
the Emergency Neurological Life Support protocols. This protocol provides a practical approach to recognition and
urgent treatment for meningitis and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric treat-
ment are discussed. The typical clinical triad of headache, fever, and neck stiffness, as well as partial manifestations 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 antimi-
crobial 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.
Keywords:  Meningitis, Bacterial meningitis, Encephalitis, Herpes simplex encephalitis, Tuberculous meningitis

Introduction patients have a predominance of meningitis or encepha-

Meningitis and encephalitis are potentially life-threaten-
ing central nervous system (CNS) infections, which often
present initially to the Emergency Department (ED).
Many of these patients are critically ill and are trans-
ported to the ED by Emergency Medical Services (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 meningoencepha-
litis. Meningitis causes fever, meningismus, and pain
(e.g., headache and neck pain), but, other than depress-
ing a patient’s mental status, does not affect cortical
brain functions (e.g., aphasia, seizure, and hemiparesis).
Encephalitis typically causes cortical disturbance, par-
ticularly altered level of consciousness and seizures. Most
*Correspondence: Katharina.Busl@neurology.ufl.edu
1
Department of Neurology/Division of Neurocritical Care, College
of Medicine, University of Florida, Gainesville, FL, USA
Full list of author information is available at the end of the article
litis, but many have features of a combined meningoen-
cephalitis syndrome. The two CNS infections that are
most important to recognize in the first hour are bacte-
rial meningitis and herpes simplex encephalitis (HSE), as
these diseases produce significant morbidity and mortal-
ity 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. A large number of survivors are left with neuro-
logic sequelae [1]. The incidence and common causative
agents have changed considerably in developed countries
since the introduction of conjugate vaccines for Hae-
mophilus influenzae B (HiB) and meningococcus [2].
Because of poverty and poor healthcare infrastructure,
they remain significantly more common in developing
countries [3]. The annual incidence of bacterial meningi-
tis in the USA is approximately 3 cases per 100,000 [1],
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 varie-
ties display seasonal and geographic variation.
Bacterial meningitis and bacterial or viral encephalitis
are medical, neurologic, and, occasionally, neurosurgi-
cal emergencies which carry substantial morbidity and
mortality despite modern medical management. Accord-
ing to one study, 48% of patients with bacterial meningi-
tis present within 24 h 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 simi-
larly to adults, neonates are more likely to present with
nonspecific findings including decreased feeding, irrita-
bility, and lethargy [3]. Meningitis should be considered
in the differential diagnosis of any lethargic, vomiting,
irritable neonate.
Fever is a major feature of these infectious illnesses.
Additional symptoms include stiff neck (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 menin-
gitis, 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 stud-
ies of patients with meningitis demonstrated that 95% of
patients had at least two of the three elements of the clas-
sic triad [5]. The absence of fever, altered mental status,
and neck pain in an immunocompetent patient essen-
tially 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 definitive clinical sign. A review
of papers on adult meningitis published between 1966
and 1997 found that Kernig’s sign was the sign most fre-
quently elicited when evaluating a patient for possible
meningitis. Kernig’s sign is elicited with the patient lying
supine and passively flexing the hips and knees to 90°.
The clinician then extends the patient’s knee, straight-
ening 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 posterior 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 cli-
nician 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 is unknown. Therefore, the absence of these
signs should not be used to rule out meningitis [6].
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 hori-
zontally at a frequency of two rotations per second. A
positive jolt accentuation test produces exacerbation of
the patient’s headache [5]. In a small study, this maneuver
had a sensitivity of 100% and a specificity of 54% for iden-
tification of meningitis.
The Emergency Neurological Life Support (ENLS) sug-
gested algorithm for the initial diagnosis, and treatment
for meningitis and encephalitis is shown in Fig. 1.
Suggested items to complete within the first hour of
evaluating a patient with meningitis and encephalitis are
shown in Table 1.
Management protocol
 • Recognize key clinical features of brain infections and identify a pos-
sible 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
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, breath-
ing, and circulation), and begin management as appropri-
ate 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 Scale (GCS), measure-
ment 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 (Table  2). Prehospital
resuscitation of patients with life-threatening infections
can expedite achievement of resuscitation goals includ-
ing achieving adequate mean arterial pressure (MAP) [7].
In a population-based retrospective study, prehospital IV
placement and fluid administration were associated with
a decreased likelihood of in-hospital mortality [8].
Initial Assessment in the Emergency Department
As with all acute medical and neurological events, the
basic ABCs of resuscitation should be evaluated imme-
diately on presentation to the ED. Vital signs (includ-
ing temperature, blood pressure, heart rate, and
 Fig. 1  ENLS meningitis and encephalitis algorithm

Table 1  Meningitis and encephalitis checklist for the first hour

Checklist

☐ 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 is a concern)
☐ Head CT, if patient neurological exam abnormal
☐ Lumbar puncture (LP), if CT results available
☐ If meningococcus remember exposure prophylaxis for contacts

respiratory rate, along with peripheral oxygen satura-
tion), a pain scale, assessment of GCS, and a rapid check
of the patient’s serum glucose level should be quickly
obtained at triage and compared to those obtained by
prehospital personnel.
In most instances, an oral temperature is adequate.
Patients who are markedly tachypneic or shivering may
not be able to keep their mouths closed for oral tem-
perature measurement and may require rectal or inva-
sive temperature measurement for accuracy. Both fever
(temperature  > 38.0  °C) and hypothermia (tempera-
ture < 36.0 °C) are compatible with CNS infection.
If the patient is normothermic, the pretest 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. Immunocompromised 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 com-
munity-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].
Patients with altered mental status are at risk of aspi-
ration, have decreased the ability to maintain a pat-
ent airway, and should be monitored for the need for
endotracheal intubation. Intubation should be considered
for any patient with a GCS ≤ 8 for airway protection.
Patients with bacterial meningitis are at risk of pneu-
monia and/or bacteremia with the same pathogen, fur-
ther reinforcing the need to closely monitor vital signs,
breathing, and hemodynamics.
Immediately after the initial assessment and triage,
patients at high risk of meningitis should be placed on
droplet precautions until further workup has been com-
pleted. Adequate 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 differen-
tial, basic metabolic panel, prothrombin time and par-
tial 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 min [9], and
the patient’s vital signs, mental status, and airway should
be reassessed every 5  min during the initial phase of
treatment (Table 2).
Similar to patients with other bacterial infections, some
patients with bacterial meningitis will be hypotensive.
This may result from sepsis or increased insensible fluid
losses from fever, tachypnea, diaphoresis, and vomiting.
In addition, bacterial meningitis, like other diseases caus-
ing septic shock, can trigger a pronounced inflammatory
response, leading to vasodilation, capillary leak, and, in
some cases, myocardial dysfunction. The initial resuscita-
tion strategy in critically ill patients with suspected men-
ingitis or encephalitis that fulfill sepsis criteria should
be identical to that recommended for other sepsis and
septic shock patients. Surviving Sepsis Campaign recom-
mends beginning resuscitation immediately in patients
with hypotension (systolic blood pressure < 90  mmHg;
MAP < 65 mmHg) or a serum lactate of ≥ 4 mmol/L with
an initial fluid challenge of 30  ml/kg of crystalloid over
20 to 30 min, in the first 3 h. These recommendations are
in light of recent randomized trials of alternative resus-
citation strategies in patients with severe sepsis and sep-
tic shock, suggesting that early identification, rapid fluid
resuscitation, timely antibiotic administration, and care-
ful monitoring may be more important than the specific
resuscitation algorithm and goals [9–13].
One liter boluses of crystalloid over 20–30 min should
be given repeatedly 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 maintenance level once goals are
achieved or when the patient demonstrates no further
fluid responsiveness [2, 10]. Norepinephrine should be
used for blood pressure support if the patient remains
hypotensive despite initial resuscitation.
The optimal translation of resuscitation recommen-
dations from sepsis to the management of patients with
CNS infections is unclear, and, in particular, the relation-
ship between aggressive early volume resuscitation and
cerebral edema is yet to be systematically investigated.
The results of the recently completed ProCESS, ProM-
ISe, and ARISE studies contribute little to this discussion
since less than 1% of the patients enrolled in ProCESS
and < 2% of the patients enrolled in ARISE and ProMISe
trials had meningitis [11–16].
Diagnostics
CBC and Blood Culture
Peripheral WBC can be elevated or depressed in patients
with CNS infection, and frequently increased immature
forms of WBCs are seen in peripheral blood [17]. A nor-
mal 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, 18, 19], 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 neu-
roimaging and LP should not delay initiation of empiric
antimicrobial therapy. Neuroimaging and LP are dis-
cussed after the section on antimicrobial treatment.
Management
Initiation of Treatment: Start Antibiotics
Appropriate antimicrobials should be started as soon as
possible after a patient with suspected CNS infection pre-
sents 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%
[20]. This was confirmed in another study of 261 patients
treated with a protocolized 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 [21].
Table 2  Prehospital and ED considerations
• Early notification (including radio report to prepare and mobilize hospi-
tal 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)
 While the applicability of these findings from the sep-
sis literature to patients with bacterial meningitis is lim-
ited by the small percentage of patients in each study
who had primary CNS infections, less rigorous studies
have demonstrated an association between time to anti-
biotic administration and outcomes for bacterial men-
ingitis, HSE, fungal CNS infections, and tuberculous
(TB) meningitis [22–25]. However, delays in antibiotic
administration are common. In a cohort of 122 patients
with documented bacterial meningitis, one study found a
mean time from triage to antibiotics of 3 h (interquartile
range, or IQR 1.6 to 4.3 h) with 90% of this delay occur-
ring after the initial physician encounter [23]. In a study
examining the impact of the 2009 changes in Swedish
recommendations 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 [26].
The choice of empiric antimicrobials is based on sev-
eral factors, including the time course of symptom pro-
gression, patient age, and other infectious risk factors.
For suspected CNS infections that evolve over hours,
bacterial meningitis, viral meningitis, and, less com-
monly, 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 considered.
Empiric treatment regimens should be chosen to cover
all etiologies that the clinical picture and limited initial
diagnostic workup supports. This may include combi-
nations of antibacterial, antiviral, and antifungal agents.
Local patterns of antimicrobial prevalence and antibiotic
resistance need to be considered [27].
Bacterial Meningitis
Worldwide, Streptococcus pneumoniae and Neisseria
meningitidis account for the majority of acute bacterial
meningitis. Neonates have a permeable blood–brain bar-
rier and are at risk of infection caused by Group B strep-
tococcus (GBS), Listeria monocytogenes, and Escherichia
coli. Empiric antibiotic therapy should include ampicil-
lin, gentamicin, and a third-generation cephalosporin
(ceftazidime or cefotaxime). Cefotaxime is currently not
available in the USA. Infants, 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 cepha-
losporin and vancomycin at doses appropriate for CNS
penetration and renal function. The elderly and immu-
nosuppressed population, including those with alcohol
dependence, are at risk for Streptococcus pneumoniae
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 [28]. In case of severe penicillin
allergy, vancomycin can be used for Gram-positive with
moxifloxacin or levofloxacin for S. Pneumoniae, N. Men-
ingitidis, H. influenzae. Trimethoprim–sulfamethoxazole
is used when Listeria is suspected and aztreonam may be
used for Gram-negative coverage (Tables 3, 4).
Adjunctive Treatment with Steroids
The value of adjunctive treatment with steroids in bac-
terial 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 dexa-
methasone in bacterial meningitis, particularly in CNS
infections caused by Streptococcus pneumoniae [19, 29].
In a Cochrane systematic review and meta-analysis [29],
it was found that corticosteroids overall reduced the rate
of any hearing loss, severe hearing loss, and neurological
sequelae. Subgroup analyses showed that corticosteroids
(a) prevented hearing loss in children with bacterial men-
ingitis, (b) reduced severe hearing loss only in children
with meningitis due to H. influenzae, (c) reduced mortal-
ity in Streptococcus pneumoniae but not for other bac-
teria, and (d) protected against severe hearing loss and
short-term sequelae for children in high-income coun-
tries, but not for those in low-income countries. This
may be due to a higher incidence 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 negate any additional ben-
efit of dexamethasone [30].
The Infectious Disease Society of America’s (IDSA)
practice guidelines from 2004 recommend discontinua-
tion of corticosteroids if it is clearly evident that Strep-
tococcus pneumoniae is not the cause of the bacterial
meningitis [28]. However, based on the more recent data
from the above meta-analysis [29], the 2016 European
Society for Clinical Microbiology and Infectious Diseases
(ESCMID) guidelines on diagnosis and treatment for
acute bacterial meningitis [31], dexamethasone should
be stopped if the patient is discovered not to have bacte-
rial 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 bacte-
rium. Adjunctive corticosteroids are also recommended
for TB meningitis regardless of disease severity [24].
Dexamethasone is the preferred corticosteroid, when
these agents are used, due to superior penetration into
the cerebrospinal fluid (CSF) and a longer half-life [29].
Corticosteroid should be given 10 to 20 min before anti-
biotics, or with the first dose of antibiotics until up to 4 h
Table 3  Dosing and target pathogens of antimicrobial therapy in adult/pediatric patients with normal renal and hepatic
function
Target Agent Children Adults

Bacterial
Group B Streptococci Ampicillin 0 to 7 days: 100 mg/kg/dose IV every 2 g IV every 4 h
Listeria 8–12 h
Gram-negative bacteria (E. coli) 8 to 28 days: 50–100 mg/kg/dose IV
every 6–8 h
> 28 days: 50 mg/kg/dose IV every
6 h (Maximum dose: 12 g/day)
H. influenzae Ceftazidime 0 to 7 days: 50 mg/kg/dose IV every 2 g IV every 8 h
N. meningitidis 8–12 h
P. aeruginosa > 7 days: 50 mg/kg/dose IV every 8 h
S. pneumoniae
H. influenzae Cefotaxime 0–7 days: 50 mg/kg/dose IV every 2 g IV every 4–6 h
N. meningitides 8–12 h
P. aeruginosa 8–28 days: 50 mg/kg/dose IV every
S. pneumoniae 6–8 h
>28 days: 75 mg/kg/dose IV every
6–8 h
H. influenzae Ceftriaxone Neonates 2 g IV every 12 h
N. meningitidis < 14 days: 50 mg/kg IV once daily
S. pneumoniae ≥ 14 days: 100 mg/kg X1, then
80–100 mg/kg/day IV once daily
Infants/children:
80–100 mg/kg/day divided every
12–24 h
(Maximum dose: 4 g/day)
S. aureus Vancomycin 15 mg/kg/dose IV every 6 h 15–20 mg/kg/dose IV every 8 -12 h
S. pneumoniae
Enterococcus species Gentamicin Neonates: 4–5 mg/kg/dose IV every 5 mg/kg/day IV in divided doses every
Listeria monocytogenes 24–36 h 8 h
S. agalactiae Infants/children: 2.5 mg/kg/dose IV
P. aeruginosa every 8 h
H. influenzae Meropenem 40 mg/kg/dose IV every 8 h 2 g IV every 8 h
N. meningitidis
S. pneumoniae
Alternative in penicillin allergy Aztreonam 30 mg/kg/dose IV every 6–8 h (Maxi- 2 g IV every 6–8 h
H. influenzae mum dose: 8 g/day)
Enterobacteriaceae
P. aeruginosa
Viral
Herpes simplex virus Acyclovir Birth to 12 years old: 20 mg/kg/dose 10 mg/kg/dose IV every 8 h
IV every 8 h
12 years or older: 10 mg/kg/dose IV
every 8 h
Varicella zoster virus Acyclovir Birth to 12 years old: 20 mg/kg/dose 10 mg/kg/dose IV every 8 h
Or IV every 8 h 5 mg/kg/dose IV every 12 h
Ganciclovir 12 years or older: 10 mg/kg/dose IV
every 8 h
5 mg/kg/dose every 12 h
Cytomegalovirus (in HIV-infected) Ganciclovir 5 mg/kg/dose every 12 h plus foscar- 5 mg/kg/dose every 12 h plus foscarnet
Off-label net until symptoms improve until symptoms improve
Fungal
Candida species Amphotericin B lipid complex 5 mg/kg/dose IV daily (may premedi- 5 mg/kg/dose IV daily (may premedi-
Aspergillus species cate with acetaminophen + anti- cate with acetaminophen + antihista-
Mucorales histamine to prevent infusion mine to prevent infusion reactions)
Mycoses reactions)
Molds
Leishmania species
Table 3  (continued)
Target Agent Children Adults

Cryptococcus Liposomal amphotericin B 3–5 mg/kg/day IV daily (may
Empiric in febrile neutropenic premedicate with acetami-
patients nophen + diphenhydramine to
prevent infusion reactions)
Mycobacterial Initial intensive phase
Empiric for strong suspicion of tuber- Ethambutol Weight-based:
culous meningitis: combination 40–55 kg: 800 mg PO daily
regimen (4 drugs) 56–75 kg: 1200 mg PO daily
76–90 kg: 1600 mg PO daily
Isoniazid 5 mg/kg/day
Pyrazinamide < 40 kg: 35 mg/kg/day
40–55 kg: 1000 mg daily
56–75 kg: 1500 mg daily
76–90 kg: 2000 mg daily
Rifampin/rifampicin 10 mg/kg once daily (maximum:
600 mg/dose)
3–6 mg/kg/day IV daily (may premedi-
cate with acetaminophen + diphen-
hydramine to prevent infusion
reactions)
<15 years and ≤ 40 kg: 15 to 25 mg/
kg/day
40–55 kg: 800 mg PO daily
56–75 kg: 1200 mg PO daily
76–90 kg: 1600 mg PO daily
< 15 years and ≤ 40 kg: 10–15 mg/kg/
day; maximum dose: 300 mg/dose
< 15 years and > 40 kg and ≥ 15 years:
5 mg/kg/day
40–55 kg: 1000 mg daily
56–75 kg: 1500 mg daily
76–90 kg: 2000 mg daily
10 to 20 mg/kg once daily (maximum:
600 mg/dose)

after the first antibiotic dose [31]. Other corticosteroids Indications for neuroimaging prior to lumbar puncture
can be used in equivalent doses if dexamethasone is not
available. There are insufficient data to recommend start- • Patient is ≥ 60 years
ing corticosteroids in neonates [28, 31]. A recent study • History of CNS disease
evaluating delayed outcomes after treatment for bacterial • Immunocompromised state
meningitis in adults found that adverse clinical outcome • History of seizure (within 1 week of presentation)
was associated with the use of adjunctive steroids [32]. • Abnormal neurologic exam findings
The overall implication of this recent report is yet to be   ◦ Impaired level of consciousness
seen.   ◦ Abnormal language
  ◦ Cranial nerve findings
Neuroimaging in Suspected CNS Infection   ◦ Motor findings
In a patient with suspected CNS infection, the perfor-   ◦ Papilledema or loss of venous pulsations on fundoscopic examina-
tion
mance of head CT and LP should not delay antimicrobial
treatment. Emergent imaging, especially in the first hour
Brain herniation after LP occurs in approximately 5%
of presentation with a suspected CNS infection, usually
of cases or less [35]. CT scan can detect brain shift and
starts with a CT scan of the head. In a study of the need
findings of impending herniation, contraindicating an LP.
for head CT prior to LP among 301 patients with sus-
However, CSF pressure may be elevated, even to levels
pected bacterial meningitis, 78% of patients had a head
where herniation may occur, in the absence of abnormali-
CT performed prior to LP [33]. Of these patients, 24%
ties on CT [34, 35]. Meningitis can be fulminant and char-
had an abnormality on the CT, and 5% had evidence of
acterized by progressive inflammation of the meninges
mass effect. Age > 60  years, immunocompromised state,
and brain swelling. Patients can herniate after LP because
history of CNS disease, altered level of consciousness,
of disease progression, or due to the inflammatory
and focal neurologic deficits were predictive of abnor-
response to bacterial proinflammatory substances liber-
mal CT findings. If CT scans were ordered only on those
ated after antibiotic administration (especially if steroids
individuals with a predictive sign of CT abnormality, the
are not given around the time of first antibiotic adminis-
rate of CT acquisition would have been decreased by 41%
tration), and not necessarily as a result of the LP [34, 35].
[33]. The IDSA Practice Guidelines for the Management
Vice versa, CSF pressure can be normal in patients with
of Bacterial Meningitis [28, 34–36] recommend that head
space-occupying lesions causing brain shift seen on CT
CT should be done prior to LP if certain features are pre-
scan, even in the stage of herniation, and the LP may lead
sent at baseline as they are likely to be associated with
to herniation even with the CSF having normal pressure
abnormal findings on a head CT (see box below).
Table 4  Empiric treatment for suspected bacterial meningitis in children and adults with normal renal and hepatic func-
tion
Empiric treatment for suspected bacterial meningitis in children and adults
Neonate/infant Infants/children Adults—immunocom- Adults—immunocompro- Healthcare-associated
(< 2 months) (≥ 2 months) petent mised

Gentamicin (4–5 mg/kg/ Ceftriaxone (80–100 mg/ Ceftriaxone (2 g IV every Cefepime (2 g IV every 8 h) Cefepime (2 g IV every 8 h)
dose IV every 24–36 h) kg/day IV divided every 12 h)
12–24 h; maximum dose:
4 g/day)
Or Or Or Or
Cefotaxime (75 mg/kg/dose Cefotaxime (2 g IV every Meropenem (2 g IV every Ceftazidime (2 g IV every 8 h)
IV q6–8 h)c 4–6 h) 8 h)
Plus Plus Plus Plus Or
Ampicillin (0–7 days: Vancomycin (15–20 mg/kg/ Vancomycin (15–20 mg/kg/ Vancomycin (15–20 mg/kg Meropenem (2 g IV every 8 h)
100 mg/kg/dose IV dose IV q6 h) dose IV every 8–12 h IV every 8–12 h)
every 8–12 h, 8–28 days:
50–100 mg/kg IV every
6–8 h)
Plus Plus (if > 50 yrs) Plus Plus
c
Cefotaxime (0–7 days: Ampicillin (2 g IV every 4 h) Ampicillin (2 g IV every 4 h) Vancomycin (15–20 mg/kg IV
50 mg/kg/dose IV every Q 8–12 h)
8–12 h, 8–28 days: 50 mg/
kg/dose IV every 6–8 h)
Or
Ceftazidime (0–7 days:
50 mg/kg/dose IV every
8–12 h
> 7 d: 50 mg/kg/dose IV
every 8 h)
Dexamethasone (0.15 mg/ Dexamethasone (10 mg IV
kg IV q6 h)—give before every 6 h)—give before
or with first dose of or with first dose of
­antibioticab ­antibioticab
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—5 mg/kg (based on the trimethoprim component) IV every 6 to 12 h
For S. Pneumoniae, N. Meningitidis, H. influenzae: replace the beta lactam with moxifloxacin 400 mg po daily or levofloxacin 750 mg IV daily
Suspected healthcare-associated meningitis: replace beta lactam with aztreonam (2 g IV every 6 to 8 h) or ciprofloxacin (400 mg IV every 8 to 12 h)
a
  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)
b
  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
c
  Cefotaxime: currently not available in the USA

[34, 35]. Because of these findings, it has been suggested
that the terms “raised intracranial pressure (ICP)” and
“intracranial hypertension” are ambiguous and should
be avoided. Instead, it should be specified whether brain
shift, or raised CSF pressure, or a combination of the two
is present [34]. Ongoing leakage of CSF after LP has been
suggested to be responsible for delayed herniation several
hours later (up to 12 h in one report) [35].
Glimaker et  al. [36] reported on data showing that
moderately to severely impaired consciousness 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 ongo-
ing) and immunocompromised 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 neuro-
logical signs or other findings indicating a space-occu-
pying 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 before head CT scan were removed [26, 36].
Of note, the IDSA guidelines on meningitis were last
updated in 2004, without availability of a similar recent
update [28].
Importantly: obtaining a cranial CT and performing an
LP should never delay antibiotic administration and ini-
tial resuscitation. With the most sensitive organisms, CSF
sterilization occurs only after 4–6 h following the initia-
tion of antimicrobials [18].
In patients who do not present with the above-men-
tioned signs, have normal mental status, and have no
focal neurologic deficits, a head CT is not always required
prior to LP. 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 infection, as it also serves the eval-
uation 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 pretest probability for these diagnoses and err on
the side of a more complete workup, 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 clinical presentation,
the evaluation of bacterial meningitis can be aborted or
adjusted to the diagnostic findings (Fig. 2).
Fig. 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 surrounding edema (white arrows) bilaterally in the parasagittal frontal lobes and right temporal lobe. He was, on further workup with
magnetic resonance imaging (MRI) of the brain, diagnosed to have multiple brain abscesses (Color figure online)
LP and CSF Analysis
CSF analysis is essential for both establishing a diagno-
sis and tailoring therapy. Informed consent should be
obtained 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 fash-
ion, and accessing the sub-arachnoid space with a spinal
needle, the OP should be measured with a manometer
prior to the collection of CSF. An elevated OP is indica-
tive of elevated ICP. If the OP is found to be greatly ele-
vated (e.g., > 400 mm H ­ 2O), 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. In order to avoid
CSF leakage and post-LP headache, the patient should
keep the head of bed less than 15° following the proce-
dure for 30 min.
CSF should be collected in a minimum of four tubes
(Table  5). CSF should be sent for cell count and differ-
ential, protein, glucose, lactic acid (if available), Gram
stain and cultures, and specific testing for pathogens as
indicated (Table  5). Newer technologies such as multi-
plex 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 [27] (Table 6).
Table 5  Tubes for collection of CSF
Tube Test
1 (and 4) Cell count and differential (if
tube 1 was turbid, and tube
4 is clear, this suggests a
traumatic tap)
2 • Protein
• Glucose
• Lactic acid
3 • Gram stain and cultures
• India ink if fungal infection
suspected
• Antigens (includes fungal)
• PCR (may also send in tube 2.
For viruses: herpes simplex,
enterovirus, etc.; Mycobac-
teria)
• IgM for viruses
• Viral culture
4 (and 1) Cell count and differential
Larger volumes of CSF increase the sensitivity of a
Gram’s stain and culture and are 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.
In patients with CSF findings suggesting bacterial
meningitis, clinicians should continue 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, sup-
portive 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 focused resus-
citation and management of sepsis. If the LP demon-
strates 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
2019 Neurocritical Care Society Guidelines for Cerebral
Edema Management (to be published at the end of 2019).
Prophylaxis
Close contacts of patients diagnosed with meningococ-
cal infection are defined as those who have had > 8 h of
contact while in close proximity of < 3 feet, or have been
directly exposed to oral secretions within 7 days prior to
onset of symptoms or until 24  h after initiation of anti-
microbials. For these close contacts, chemoprophylaxis
should be administered as early as possible, i.e., within
24 h. Regimens for adults include either Rifampin 600 mg
orally every 12 h for 2 days, a single oral dose of Cipro-
floxacin 500  mg or single dose of intramuscular Ceftri-
axone 150  mg. Vaccination with meningococcal vaccine
to boost herd immunity and promote outbreak control is
recommended when there is a meningococcal outbreak.
Encephalitis
Encephalitis is defined by the presence of an inflam-
matory process of the brain in association with clinical
evidence of neurologic dysfunction. The majority of the
pathogens that cause encephalitis are viruses. However,
other pathogens such as bacteria, mycobacteria (TB), spi-
rochetes, Rickettsia, Ehrlichia, fungi, and protozoa can
also cause encephalitis.
Despite extensive testing, the etiology of encephalitis
remains unknown in most patients [38]. 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 [38]. Symp-
toms and signs of encephalitis and meningitis are similar;
for example, decreased level of consciousness may be pre-
sent in meningitis due to inflammation of the brain tissue,
but not necessarily due to direct infection of the brain tis-
sue. Noninfectious CNS diseases (e.g., vasculitis, collagen
vascular disorders, autoimmune and paraneoplastic syn-
dromes) 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 defini-
tive treatment, but specific agents should be sought and
identified, when possible, which is important for progno-
sis, potential prophylaxis, and counseling of patients and
family members, as well as public health interventions.
Diagnosis of encephalitis requires an LP, which may
need to be delayed if the previously mentioned contrain-
dications 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 h 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 [38]. If the MRI is being performed
before the LP, the initiation of appropriate antimicrobi-
als should never be delayed until the imaging is done.
Detection of IgM antibodies in CSF caused by numer-
ous viruses is considered to be diagnostic of neuroinva-
sive disease. Cultures of the CSF are of limited value in
determination of viral causes but are helpful in diagnos-
ing bacterial and fungal infections. The PCR test greatly
increases the ability to diagnose infections of the CNS,
especially viral infections caused by herpes viruses,
Table 6  CSF analysis
LP findings WBC RBC CSF glucose/ CSF protein Organisms
in meningitis serum glu-
cose ­ratiob

Normal ≤ 5 per high-powered field ≤ 5 per HPF > 0.6 < 50 mg/dL None
(HPF)a
Bacterial 100’s to 1000’s per HPF, neu- Usually normal < 0.6 > 50 mg/dL Seen on Gram’s stain in
trophil predominance approximately 70% of cases
Non-herpes virus 10 to several 100 per HPF, None per HPF > 0.6 < 50 mg/dL usually. Absent on the Gram’s stain
lymphocyte predomi- If elevated it is usu- Despite these characteristics,
nance ally < 100 mg/dL continue antibiotics until
CSF culture results are nega-
tive and clinical improve-
ment is demonstrated
Herpes virus 100’s per HPF typically with 10–100 per HPF or > 0.6 Either < 50 mg/dL or Absent on the Gram’s stain
a lymphocytic predomi- higher mildly elevated, usu- The presence of seizures and
nance ally < 100 mg/dL findings of uni- or bilateral
hypodensities with or
without hemorrhage in the
temporal lobes on brain
MRI, and rarely on brain CT
scans, are also compatible
with this diagnosis
Fungal May be normal or Absent Decreased or > 50 mg/dL, often highly India ink stain can detect
If elevated it is usually 100 normal elevated Cryptococcus
to 400’s, lymphocyte
predominance
Tuberculosis Elevated, usually 100 to Absent < 0.6 > 50 mg/dL Acid-fast bacilli occasionally
400’s, with lymphocyte seen on smear with Kinyoun
predominance or Ziehl–Neelsen stains
a
 HPF = High power field
b
  An absolute normal range cannot be given for CSF glucose; it is usually considered to be normal when the CSF glucose/serum glucose ratio is > 0.6. The CSF glucose
levels generally do not rise above 300 mg/dL (16.7 mmol/L) regardless of serum levels, so the ratio may decrease with rising serum glucose level. In neonates, the CSF/
serum glucose ratio varies more than adults and is generally higher in normal CSF [37]. Elevated glucose level in the CSF only occurs with hyperglycemia, and not with
any other CNS pathologies

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 con-
tinues 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 gener-
ally limited to herpes viruses (especially herpes simplex
virus) and HIV, treated with acyclovir and antiretrovirals,
respectively [38] (Fig. 3).
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.
Hydration should be sufficient to achieve normovolemia,
thereby avoiding the complication of acyclovir-associated
renal failure. For varicella zoster virus (VZV), acyclovir is
recommended, but ganciclovir can be given alternatively.
For cytomegalovirus, the combination of ganciclovir plus
foscarnet is recommended (see Table 3).
The treatment for non-herpetic viral encephalitis is
primarily supportive in nature. Many of these patients
will have a significantly depressed level of conscious-
ness, making close observation and airway management
crucial. For West Nile virus, there is risk of respiratory
decompensation from neuromuscular weakness second-
ary to spinal cord involvement and depression of con-
sciousness. Oxygen saturation may fall due to aspiration
or hypoventilation and ­CO2 may rise as an early indicator
of ventilatory failure. Admission to the ICU for observa-
tion is frequently warranted.
Other forms of viral encephalitis, such as those caused
by the Arboviruses, including West Nile virus, may also
have a subacute presentation [39]. There are no pharma-
cotherapeutic interventions for these encephalitides, but
until exclusion of HSE can be verified, empiric acyclovir
is reasonable.
Mycobacterial CNS Infection
TB meningitis is another CNS infection to be consid-
ered in the early differential diagnosis, especially if
there has been a subacute and more protracted course
of onset of illness: In a patient presenting with a symp-
tom duration of more than 5  days, particularly if the

Fig. 3  CT and MRI brain of herpes encephalitis. A 75-year-old male
presenting with 2 days of altered mental status, low-grade fever and
seizure. a CT scan of head shows extensive edema involving the right
medial temporal lobe with hemorrhagic conversion. b MRI brain
(FLAIR sequence) shows extensive vasogenic edema involving the
right medial temporal and right medial orbitofrontal lobes suggestive
of herpes encephalitis
patient is immunocompromised, the diagnosis of TB
meningitis should be considered [40]. Tuberculosis
is more prevalent in high-risk groups, including the
homeless, nursing home residents, ethnic minorities,
and persons infected with HIV [41]. Cranial nerves
are affected in 20 to 30%, most commonly III, VI, VII,
and VIII [42]. TB meningitis can be complicated by
hydrocephalus, tuberculomata, brain abscess forma-
tion, and disorders of sodium, and water metabolism
[42]. 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 [43]. Therefore, in practice, a
combination of clinical presentation, CSF appearance,
imaging, and acid-fast bacilli at other sites is used to
make a provisional diagnosis. CSF OP is usually mod-
erately elevated (18–30 cm ­H2O), CSF glucose is often
depressed (< 40  mg/dL), and CSF protein is usually
elevated [41]. Acellular CSF profiles may occur [44].
PCR assays have improved the diagnostic process in TB
meningitis with sensitivity of 56–76% and specificity of
89–98%, depending on the assay [45, 46]. Imaging 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 [42].
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 similar to
any other bacterial meningitis [47].
Fungal Meningitis or Encephalitis
Fungal CNS infections are highly variable in clinical pres-
entation and need to be considered 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.
As with other CNS infections, fast identification and
treatment initiation significantly affect the odds of a
better outcome [25]. Typical CSF findings include lym-
phocytic pleocytosis (few to several hundreds per HPF)
and for certain organisms also with eosinophilic pre-
dominance. CSF glucose is decreased, and CSF protein
is generally elevated (up to 250  mg/dL or beyond). If
CSF acquisition via LP is difficult or impossible, it can
be an indicator of very high (> 1  gm/dL) CSF protein
and obstructive hydrocephalus. Empiric amphotericin B
should be administered during diagnostic testing.
Pediatric Considerations
Bacterial meningitis is an important contributor to pedi-
atric morbidity and mortality [48]. Diagnosis can be diffi-
cult in infants who often have nonspecific manifestations
such as fever, hypothermia, lethargy, irritability, respira-
tory distress, poor feeding, vomiting, or seizures. In older
children, clinical manifestations include fever, headache,
photophobia, nausea, vomiting, and decreased mental
status [49]. The major pathogens involved are dependent
on the age of the child [28, 48]:
•  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 bacilli [50].
• < 2 months—GBS, Listeria monocytogenes, Strepto-
coccus pneumoniae, Neisseria meningitidis, Haemo-
philus influenzae.
•  2 to 23  months—Streptococcus pneumoniae, GBS,
N. meningitidis, Haemophilus influenzae [28, 51].
•  2 to 10 years—Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae.
•  11 to 17  years—Neisseria meningitidis, Streptococ-
cus pneumoniae.
Bacterial meningitis is a true pediatric medical emer-
gency, and immediate diagnostic and therapeutic steps
must be taken (Fig.  4). The initial management should
include evaluation and restoration of normal oxygena-
tion, ventilation, and perfusion. For children with a
GCS ≤ 8 and/or lack of airway protective reflexes, intu-
bation for airway protection is advised. Similar to adults,
pediatric patients with bacterial meningitis may also pre-
sent with signs and symptoms of septic shock. Per the
Pediatric Septic Shock Guidelines [28, 51] 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 pres-
sure for age. If shock is fluid refractory, epinephrine for
cold shock or norepinephrine for warm shock should
be initiated. Supportive care should also include detec-
tion and management of hypoglycemia, acidosis, and
coagulopathy.
LP and blood cultures should be performed without
delay, and empiric antibiotics should be given immedi-
ately following its completion. If performance of blood
cultures or the LP is not possible or must be delayed
(i.e., due to the need to obtain brain imaging), initiation
of antibiotic therapy should not be postponed. Children
with mass effect on brain imaging or signs  of intracra-
nial hypertension are at higher risk of cerebral herniation
when a LP is performed. If signs of mass effect or intrac-
ranial 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 management of cerebral per-
fusion pressure improves outcome in pediatric patients
with acute CNS infections [28].
An empiric antibiotic regimen (Table  4) for
infants < 2 months of age should include ampicillin, gen-
tamicin, and cefotaxime [28]. In older infants, children,
and adolescents, the appropriate empiric treatment
regimen should cover penicillin-resistant S. pneumo-
niae and N. meningitidis [51]. 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 Pneu-
mococcus. In case of penicillin allergy, alternatives such
as aztreonam or levofloxacin (depending on organism
targeted) should be considered. The empiric antibi-
otic regimen should be broadened in infants and chil-
dren with immune deficiency, penetrating head trauma,
other anatomic defects, or if the development of men-
ingitis is healthcare-related [52]. The recommended
empiric therapy for these patients is vancomycin plus
an antipseudomonal beta lactam (such as cefepime, cef-
tazidime, or meropenem), per the practice guidelines of
the IDSA [52].
Adjunctive therapy with dexamethasone has been
discussed previously. The American Academy of Pedi-
atrics Committee on Infectious Diseases suggests that
dexamethasone 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 [53]. The 2016 ESCMID guidelines
[31] state that based on expert consensus, dexameth-
asone can still be started up to 4  h after initiation of
antibiotic treatment. Finally, there are insufficient data
to recommend starting corticosteroids in neonates [28,
29, 31].
Children with encephalitis present with symptoms
of CNS dysfunction including alterations of conscious-
ness, cortical dysfunction with focal neurologic signs,
and ataxia. Additional signs and symptoms include fever,
seizures, and abnormal neuroimaging [54]. As in the case
of children with bacterial meningitis, the initial manage-
ment includes restoration of normal oxygenation, ventila-
tion, and perfusion, as well as detection and management
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 previously healthy children
present with acute paralysis [51]. While encephalitis from
enterovirus is relatively well known, there is emerging
evidence that AFM may be a delayed response to respira-
tory enterovirus infection, particularly Enterovirus D68.
Typically, children have a viral respiratory or less com-
monly gastrointestinal prodrome, with fever, headache,

Fig. 4  Approach to suspected CNS infection in infants and children
neck stiffness, and myalgia in varying combinations. This
is followed by a rapidly progressive 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 longitudinally extensive predominantly gray mat-
ter involvement. Treatment is supportive including res-
piratory support.
Finally, several infectious diseases previously thought
to be eradicated by immunizations have been increas-
ingly 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-asso-
ciated meningitis is generally benign, although long-term
sequelae from encephalitis are common.
Nursing Considerations
The role of the nurse for a patient who presents with
suspected meningitis includes assisting the providers
with the initial examination, airway and hemodynamic
stabilization, obtaining intravenous assess, and prompt
administration of antibiotics. Nursing assessment
should include establishing an initial neurologic exami-
nation and baseline vital signs. Respiratory 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, depth of respiration, etc. is
important in identifying patients who need endotra-
cheal intubation. Hemodynamic compromise can occur
in patients with meningitis including sepsis and/or
septic shock. The bedside nurse should closely moni-
tor patient’s volume status and hemodynamics paying
particular attention to blood pressure and heart rate
trends. Hyperthermia can occur secondary to infection
[55]. Antipyretics and other measures of fever control
should be instituted promptly and as needed. Vigilant
monitoring for complications of meningitis and enceph-
alitis includes signs or symptoms of cerebral edema
(e.g., Cushing’s triad), increased ICP, hydrocephalus
and seizures with prompt notification to provider teams
with any change in status. Seizure precautions should
be in place for all patients with meningitis and enceph-
alitis including keeping the bed in low position with
padded side rails and suction and oral airway available
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, pretransfer physical and neurological exam
☐ Ongoing concerns, active issues, outstanding studies/tests
☐ Infectious precautions applied/required

Table 8  Meningitis and encephalitis—sample structured communication

Communication—elements to include

☐ Age
☐ GCS
☐ Airway status
☐ Hemodynamic condition
☐ Presumed pathogen (bacterial, viral, etc.)
☐ Imaging findings
☐ Antibiotics, steroids
☐ Precautions necessary
Sample sign-off narrative:
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 min into the trans-
port, 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 101 F. 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

at bedside [55]. Finally, nurses should be vigilant about
enforcing droplet and isolation precautions to minimize
spread of infection.
Communication
Transfer of care to the accepting healthcare team is an
important step to maintain continuity 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 healthcare
team.

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 menin-
gitis
• 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 min before, with or up to
4 h after antibiotics for bacterial meningitis. Further continuation of
steroids depends on the specific bacteria identified
Author details
1
 Department of Neurology/Division of Neurocritical Care, College of Medi-
cine, University of Florida, Gainesville, FL, USA. 2 Department of Internal
Medicine/Division of Critical Care, Boone Hospital Center, BJC Health Care,
Columbia, MO, USA. 3 Departments of Emergency Medicine and Neurology,
University of Michigan, Ann Arbor, MI, USA. 4 Department of Critical Care
Medicine, Mayo Clinic, Jacksonville, FL, USA. 5 Department of Child Health, Uni-
versity of Arizona College of Medicine, Phoenix, AZ, USA. 6 Cardon Children’s
Medical Center, Mesa, AZ, USA.
Acknowledgements
The authors are grateful for the contributions and insight provided by the fol-
lowing reviewers: Natalie Gofman, Pharm.D., BCPS, BCCCP; Yasser Abulhasan,
MBChB, FRCPC.
Author contributions
All authors contributed to drafting and/or revising the manuscript.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
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