Abstract:

This article provides a review of the

evaluation and management of
meningitis in young children. It
highlights the most common causes
of meningitis and the most current
Meningitis in
treatment recommendations. Since
the development of the hemophilus
and pneumococcal conjugate
Children:
vaccines, pediatric bacterial
meningitis has been diagnosed less
frequently. Viral meningitis is far
Diagnosis and
more common and tends to be a less
severe disease. It is very important
to maintain a high index of suspicion
and a low threshold for evaluation of
Treatment for the
meningitis in febrile young infants
younger than 3 months. Emergency
Keywords:
meningitis; encephalitis; children;
herpes simplex
Clinician
Gabriella Cardone Richard, MD,
Marcos Lepe, MD

*Texas Children's Hospital, Houston, TX;
Universidad Autnoma de Baja California.
Reprint requests and correspondence:
Gabriella Cardone, MD, Texas Children's
Hospital, 6621 Fannin Suite A-210,
Houston, TX 77030.
gabriellamd@me.com
1522-8401/$ - see front matter
2013 Elsevier Inc. All rights reserved.
A
59-day-old girl, former full-term healthy infant, pre-
sented to the emergency department with a 1-day
history of fever to 102F, poor feeding, and increased
fussiness. The mother remembers brief moments when
the infant rolled her eyes for a few seconds and abnormal arm
movements. The physical examination was unremarkable, in-
cluding a flat fontanel and normal capillary refill. Blood, urine, and
cerebrospinal fluid (CSF) were obtained.
A complete blood count revealed a white blood cell (WBC)
count of 13 480 with a left shift. The CSF revealed the following:
WBC 1519/mm 3 (77% neutrophils and 4% lymphocytes); red
blood cells (RBC) 3270/mm 3; glucose 98 mg/dL (vs a venous
glucose of 111); and protein 205 mg/dL. She was admitted to the
hospital and started on empiric vancomycin, ceftriaxone, and
acyclovir. Cerebrospinal fluid culture was positive for Gram (+)
organisms and grew group B streptococcus (GBS). Results of
herpes simplex virus (HSV) and enterovirus polymerase chain
reaction (PCR) assays were negative. When the diagnosis of GBS
meningitis was confirmed, acyclovir was discontinued. After a 2-
week hospitalization, the baby was discharged home in
excellent condition.

146 VOL. 14, NO. 2 MENINGITIS IN CHILDREN / RICHARD AND LEPE

 MENINGITIS IN CHILDREN / RICHARD AND LEPE VOL. 14, NO. 2 147
INTRODUCTION AND DEFINITIONS
Meningitis is an inflammation of the membranes
surrounding the central nervous system: dura
mater, arachnoid mater, and pia mater manifested
by CSF pleocytosis. 1-3 It reflects an inflammation
of the arachnoid mater and the CSF in both the
subarachnoid space and the cerebral ventricles.
Meningitis is caused by a myriad of pathogens that
can incite different symptoms, often making
diagnosis difficult. In younger age groups before
speech development, frequently few signs and
symptoms can be detected.
Meningitis, in particular bacterial meningitis,
carries very high morbidity rates (21%-56%),
which stresses the importance of prompt and
correct treatment. 3 The mortality of bacterial
meningitis when untreated can approach 100%.
There is also a great emphasis on promptly
diagnosing and empirically treating meningitis
because of the risk of permanent neurologic
sequelae, which ranges from 10% to 30%,
according to some sources for bacterial meningi-
tis. 4-7 Some authors argue that morbidity and
mortality vary with geographical location and age
and from one pathogen to another. 7 It is not
surprising that failure to diagnose pediatric
meningitis constitutes one of the most common
causes of medical malpractice cases within
pediatric emergency medicine. 4,8,9 There must
always be a high degree of suspicion whenever
certain symptoms arise. Table 1 lists some of the
nonspecific presenting complaints of infants with
meningitis.
Encephalitis, which is defined as an inflammatory
process of the brain parenchyma, shares some of the
same etiology and symptoms. 10 Encephalitis repre-
sents further disease invasion or progression. 11 The
presence or absence of normal brain function
distinguishes meningitis from encephalitis. The
presence of flaccid paralysis and reduced reflexes
is a manifestation of inflammation of the spinal cord,
referred to as myelitis.
Aseptic meningitis is a clinical syndrome in
which cultures for routine bacterial pathogens are
negative and there were no antibiotics given before
the lumbar puncture (LP). The causes can be
infectious and noninfectious, but viruses remain
the most common cause. For this reason, aseptic
meningitis and viral meningitis are frequently
interchangeable terms. 12-15
This article will provide a review of age-
appropriate clinical presentations, current diag-
nostic methods, and treatment options available to
the emergency clinician.
TABLE 1. Signs and symptoms of meningitis in
infants.
General Signs Specific Signs
Fever or hypothermia Convulsions
Respiratory distress or apnea Bulging fontanelle
Jaundice
Drowsiness
Reduced feeding
Failure to thrive
Unconsciousness
Lethargy
High-pitched cry
Vomiting
Irritability
Data from: the World Health Organization 37 and Curtis et al. 4
ETIOLOGY AND PREDISPOSING FACTORS
Bacteria, viruses, fungi, and parasites are consid-
ered infectious causes and are described in
Table 2. 16,17 Noninfectious causes include drugs,
neoplastic disease, and other systemic diseases. 3
Viral pathogens remain the number 1 cause of
meningitis in the United States. 14,18,19 The most
common viruses that cause meningitis are enterovi-
ruses. Other frequent viral pathogens include
arboviruses (eg, St Louis encephalitis virus, tick-
borne encephalitis virus, dengue virus, West Nile
virus), and herpesviruses (eg, Epstein-Barr virus,
herpesvirus types 1 and 2, varicella-zoster virus). 18
Fortunately, several diagnostic methods have been
developed to diagnose viral or aseptic meningitis, the
most important being reverse transcriptase PCR,
which is increasingly being used as the incidence of
aseptic meningitis rises. 20 PCR is often more readily
available than the viral culture, which can still be
sent as a confirmation.
Certain viruses produce some clues to the
etiology, some of which can be found in Table 2.
Findings frequently associated with viral infections
such as conjunctivitis, rash, herpangina, hand-foot-
mouth disease, generalized lymphadenopathy, oral
or genital ulcers, chicken pox, parotid swelling, and
others, should be noted.
Since the development and Food and Drug
Administration acceptance and use of the Haemo-
philus influenzae B (Hib) vaccine for use in infants,
there has been a tremendous decrease in its
incidence as a causative agent of meningitis. 21-24
Because of this, in the 1990s, Streptococcus pneu-
moniae became the primary cause of bacterial
148 VOL. 14, NO. 2 MENINGITIS IN CHILDREN / RICHARD AND LEPE

TABLE 2. Clinical indicators of viral etiologies of central nervous system infections.

Clinical Indicators Etiology Meningitis Encephalitis

Enteroviruses
Hand-foot-mouth disease, herpangina, pharyngitis, Coxsackie A and B Common Rare
conjunctivitis, pleurodynia, myopericarditis, rash
Rash Echoviruses Common Rare
Flaccid paralysis Polioviruses Common Rare
Arboviruses
Rash, mosquito exposure West Nile virus Uncommon Common
Mosquito exposure La Crosse (California) encephalitis virus, Common Common
Western equine encephalitis virus,
St Louis encephalitis virus
Mosquito exposure Eastern equine encephalitis virus Rare Common
Tick exposure Powassan virus Uncommon Common
Herpesviruses
Lymphadenopathy, pharyngitis, Cytomegalovirus and Epstein-Barr virus Uncommon Common
immunocompromised host
Oral lesions Herpes simplex type 1 Rare Common
Genital ulcers, sacral radiculopathy Herpes simplex type 2 Common Rare
Vesicular rash (chicken pox), shingles Varicella zoster virus Common Rare
Other viruses
Fever, cough, sore throat, vomiting, headache, diarrhea Influenza virus Rare Common
Intravenous drug use, risky sexual behavior Human immunodeficiency virus Common Common
Animal exposure; prodrome of nonspecific symptoms Rabies virus Rare Common
(fever, headache, malaise, myalgia, cough, sore throat,
nausea, vomiting)
Rodent pets or contact with rodent urine or droppings Lymphocytic choriomeningitis virus Common Uncommon
Parotitis unvaccinated or partially vaccinated Mumps virus Common Uncommon
individuals
Conjunctivitis, cough, coryza in unvaccinated Measles virus Common Rare
or partially vaccinated individuals

meningitis in children, 21,22 thus marking 2 distinct
eras: a pre-Hib vaccine era and a post-Hib vaccine
era. 23 Another vaccine of great importance is the S
pneumoniae vaccine (pneumococcal conjugate vaccine
[PCV]). The vaccine is presently composed of 13
polysaccharides or serotypes and 2 cross-reactive
serotypes. These and the newly identified serotypes
were responsible for most cases (80%) of invasive
pneumococcal disease in the United States between
2000 to 2010. 21,25,26 After the introduction of this
vaccine, several sources have reported a decreased
incidence of pneumococcus as the cause of menin-
gitis in unimmunized patients. 27,28 With the intro-
duction of both vaccines, the incidence of bacterial
meningitis declined in all groups except children
younger than 2 months. 28,29 Currently, S pneumoniae
remains the most frequent cause of bacterial
meningitis in children. 21,27,29-32 Table 3 summarizes
some predisposing factors for bacterial meningitis.
There are other factors that increase the risk for
bacterial meningitis such as penetrating trauma,
recent exposure to an individual with meningococ-
cal or Hib meningitis, and anatomical defects such as
dermal sinus or a urinary tract anomaly. 33
CLINICAL PRESENTATION, DIAGNOSIS,
AND MANAGEMENT
Patients 0 to 30 Days Old
The classic signs of meningismus such as neck
stiffness, headaches, photophobia, and Kernig or
Brudzinski signs are not present either because of
the immature nervous system in the newborn and
infant or because the patient's not-yet developed
speech makes it increasingly difficult to rely on the
usual adult signs and symptoms. 4,34,35 Instead, in
the neonate and infant, one must rely on other
nonspecific signs such as abrupt onset of fever,
accompanied by decreased activity, decreased
feeding, irritability, failure to thrive, and sleepiness,
among others (Table 1). 4-37
 MENINGITIS IN CHILDREN / RICHARD AND LEPE VOL. 14, NO. 2 149

TABLE 3. Entry site, age, and predisposing factors for bacterial meningitis.
Pathogen Entry Site Age Range Predisposing Factors

N meningitidis Nasopharynx All ages None, rarely complement deficiency

S pneumoniae Nasopharynx, direct extension across skull All ages Conditions that predispose to pneumococcal
fracture, or from contiguous or distant bacteremia, choclear implants, defects of ear
foci of infection ossicle, cribiform plate fracture, and basilar
skull fracture with otorrhea
S aureus Skin, foreign body, bacteremia All ages Surgery and foreign body such as ventricular
drains, endocarditis, cellulitis, and skin ulcerations
L monocytogenes Gastrointestinal tract and placenta Neonates Cell mediated immunity defects (eg, transplants
and use of steroids), pregnancy, liver disease,
and malignancy)
Coagulase-negative Foreign body All ages Foreign bodies such as ventricular drains, surgery
staphylococci
Gram-negative bacilli Various Neonates Neurosurgery, ventricular drains, advanced
medical illness
H influenzae Nasopharynx, contiguous spread from Nonvaccinated Diminished humoral immunity
local infection children, adults

Neonates are at increased risk for severe sys-
temic disease, particularly by HSV, with progres-
sion to encephalitis with seizures and/or focal
neurologic findings. 36 They can manifest with
systemic presentations that include pneumonia,
hepatitis with hepatic necrosis, myocarditis, and
necrotizing enterocolitis. 36 In the above presenta-
tions, disseminated intravascular coagulation and
findings of sepsis can mimic overwhelming bacterial
infections.
To optimize evaluation and management, one
should obtain a thorough history in neonates with
fever greater than 100.4F or 38C. The history
should include perinatal and birth history (mater-
nal fever, maternal GBS status, and sexually
transmitted infections, in particular HSV, gonor-
rhea, and chlamydia). It should also include
history of prolonged rupture of membranes and
nursery events, sick contacts and daycare pres-
ence, associated symptoms (vomiting, diarrhea,
cough, congestion, etc), and changes in behavior,
feeding, and activity.
Along with the aforementioned clinical charac-
teristics, there are also other key points to have in
mind. One would be the age of the patient. There are
well-defined differences between cases of meningitis
within the first month of life and cases described in
infants older than 60 days. The former group is of
special mention because the highest incidence of
bacterial meningitis is seen within the first month of
life. 30 The physical examination should readily
identify the patient who requires resuscitation vs
the well-appearing infant. Vital signs including pulse
oximetry and capillary refill should be documented,
and signs of toxicity such as inconsolability, poor
perfusion and tone, and lethargy should be noted. A
bulging fontanelle typically presents late in the
illness. Nuchal rigidity can be present in one third of
the patients aged 0 to 6 months and 95% of patients
older than 19 months. 38
There are multiple studies that document the use
of peripheral WBCs in the evaluation of all febrile
young infants. These studies are not the focus of this
review. Despite their common use, there is

TABLE 4. Cerebrospinal fluid analysisreference ranges.

Age WBC Glucose CSF Glucose/Blood Glucose Protein

Preterm 9 (0-25 WBCs/mm 3); 57% PMNs 50 (24-63 mg/dL) 55%-105% 115 (65-150 mg/dL)
Term 8 (0-22 WBCs/mm 3); 61% PMNs 52 (34-119 mg/dL) 44%-128% 90 (20-170 mg/dL)
Child 0-7 WBCs/mm 3; 0% PMNs 40-80 mg/dL 50% 5-40 mg/dL

Data from: McMillan JA, Feigin RD. Oski's Pediatrics: Principles & Practice. Philadelphia, Pa: Lippincott Williams &
Wilkins; 2006.
150 VOL. 14, NO. 2 MENINGITIS IN CHILDREN / RICHARD AND LEPE
significant variability in the sensitivity and specific-
ity of this test in determining the presence or
absence of meningitis, and the decision to perform a
blood culture and a lumbar puncture (LP) should
not be based solely on the WBC count.
Various observational studies indicate that the
use of C-reactive protein and procalcitonin en-
hances the ability to detect serious bacterial
infection and invasive bacterial illness. These tools
in combination with a urine dipstick, WBC, and
absolute neutrophil count (ANC) can direct the
clinical management. Procalcitonin has variable
performance by age and is not usually available at
bedside, limiting its use. 39-41
An LP should be performed in all febrile children
younger than 28 days and in all ill-appearing febrile
infants and should be strongly considered in febrile
young infants treated with empiric antibiotics
before the evaluation. The presence of invasive
infection including osteomyelitis, abscess, mastitis,
omphalitis, or cellulitis obligates the consideration
of LP, as does the presence of seizures. Reference
CSF ranges are displayed in Table 4.
Patients Older Than 1 Month
Clinical Presentation and Diagnosis
Most infants older than 1 month with bacterial
meningitis present with fever and signs of inflam-
mation of the meninges (nausea, vomiting, head-
ache, back pain, nuchal rigidity, confusion,
anorexia, irritability). Paradoxical irritability,
when attempts to console the infant cause further
distress or pain, is commonly reported by parents of
children with serious illness, particularly meningi-
tis. Frequently, upper respiratory infections precede
the illness. There is no single sign that is pathogno-
monic for the disease. 42 The triad of fever, neck
stiffness, and mental status changes is present only
in 44% of adults with meningitis and less frequently
in children, or may not occur until late in the
course. 32 Papilledema is a rare finding in acute
bacterial meningitis, and subdural empyema, brain
abscess, and venous sinus occlusion should be ruled
out if papilledema is seen on clinical examination. 42
Seizures occur in 20% to 30% of patients before
hospitalization. 15
The manifestations of viral meningitis are generally
similar to those of bacterial meningitis but are usually
less severe. 43 Certain viruses provide some clues to
the etiology (Table 2). Findings frequently associated
with viral infections such as conjunctivitis, rash,
herpangina, hand-foot-mouth disease, generalized
lymphadenopathy, oral or genital ulcers, chicken
pox, or paratid swelling should be noted. Viral
meningitis may be suspected based on epidemiologic
data and clinical features, but these are unreliable in
the earliest stages of bacterial meningitis; therefore,
the approach should be similar to that of bacterial
meningitis until the identification of the pathogen is
accomplished or the etiology for the symptoms is clear
to the practitioner.
In meningococcemia, an erythematous maculopap-
ular eruption may be present initially and be followed
by the development of petechiae and purpura. 42
Evaluation
As discussed earlier, meningitis, in particular
bacterial meningitis, is an emergency and the
diagnostic interventions have to be done immedi-
ately. A careful history and physical examination,
blood tests, and LP ideally should be performed
before the administration of antibiotics. However, in
fulminant cases (eg. decreased blood pressure),
resuscitation and shock management take priority,
and a blood culture should be obtained before
antibiotics, if at all possible, with the LP performed
as soon as it is feasible. The current criterion
standard in establishing the diagnosis of meningitis
in infants is obtaining CSF and then analyzing its
contents: protein, glucose, cell count and differen-
tial, Gram stain, and culture. 4,34,35,44,45 Typical CSF
findings in meningitis are displayed in Table 5.
The presence of pleocytosis is strongly associated
with meningitis. In addition, it is generally accepted
that viral meningitis has fewer and more vague
symptoms than bacterial meningitis. 43 The CSF
findings can direct further diagnostic tests such as
PCR to look for viral genomes. 46 The CSF results
aid the physician in deciding whether to give
antibiotics for bacterial causes, acyclovir for HSV,
or supportive care for other viral causes. 20 If
bacterial meningitis is suspected and the LP is
contraindicated or unsuccessful or if neuroimaging
is needed before performing the LP, antibiotics
should not be delayed. Additional studies including
serology for measles, mumps, arboviruses, varicella,
Ebstein-Barr virus, lymphocytic chorionic menin-
gitis virus (LCMV), HIV, syphilis, and Lyme disease
may be sent if indicated.
How to Interpret CSF Reference Ranges
The CSF WBC count in acute bacterial meningitis
is usually more than 1000/high-power field, with
predominance of neutrophils, but in early pre-
sentations, few or no WBC may be present. 13 The
glucose is less than 40 mg/dL (2.2 mmol/L), and the
ratio of the CSF to blood glucose concentration is
usually depressed (b 0.6). The CSF protein ranges
 MENINGITIS IN CHILDREN / RICHARD AND LEPE VOL. 14, NO. 2 151

TABLE 5. Cerebrospinal fluid analysis in meningitis.

Total WBC Count (cells/L) Glucose (mg/dL) Protein (mg/dL)

N 1000 100-1000 5-100 b 10 a 10-45 b N 250 c 50-250 d

Less Some cases Encephalitis Encephalitis TB meningitis; Neurosyphilis; TB meningitis

common of mumps fungal meningitis some viral
and LCMV infections
(such as mumps
and LCMV)
More Bacterial Bacterial or Early bacterial Bacterial Bacterial Bacterial Viral meningitis;
common meningitis viral meningitis; meningitis; viral meningitis meningitis meningitis Lyme disease;
TB meningitis meningitis; neurosyphilis
neurosyphilis;
TB meningitis

TB indicates tuberculosis, LCMV indicates lymphocytic chorionic meningitis virus.

Data from: Feigin RD, Cutrer WB. Bacterial meningitis beyond the neonatal period. In: Feigin and Cherry's Textbook of Pediatric
Infectious Diseases, 6th ed, Feigin RD, Cherry J, Demmler-Harrison GJ, Kaplan SL (Eds), Saunders, Philadelphia 2009. p.439.
a
Less than 0.6 mmol/L.
b
Ranging from 0.6 to 2.5 mmol/L.
c
Greater than 2.5 g/L.
d
Ranging from 0.5 to 2.5 g/L.

between 100 and 500 mg/dL. In a traumatic LP, the
protein concentration may be increased; it can be
corrected by subtracting 1 mg/dL for every 1000
RBC/L. 42,47 The presence of polymorphonuclear
(PMN) cells is not pathognomonic for bacterial
meningitis because aseptic meningitis can have an
early neutrophilic predominance. With a traumatic
LP, it is common to use cell count correcting
formulas, none of which have total confidence, but
a commonly used formula is to subtract 1 WBC for
every 1000 RBCs/L. 48 The presence of immature
bands does not help distinguish between viral and
bacterial etiologies (Table 5).
In viral meningitis, the cell count typically ranges
from 10 to 500 cells/L. Some exceptions have been
described with particular viruses, as previously
published. 14,19,49,50 Normal counts can be seen early
in the course of the infection. The predominance of
mononuclear cells is the norm in viral meningitis, but
as described earlier, PMN cells can be seen in the first
24 to 48 hours of the illness. 19 Glucose is normal or
slightly reduced, but usually 40% of the serum value or
greater, and CSF protein is less than 100 mg/dL. Gram
stain of the CSF should be negative for bacteria.
Improvement of symptoms after an LP is also
frequently observed, even in young infants.
Samples of CSF should be sent for PCR analysis
for enterovirus, and in appropriate patients, for
herpes simplex and West Nile viruses. Rectal swabs
and throat swabs may be sent for viral culture to
confirm the PCR results in enteroviral illness. PCR
has largely replaced viral cultures in the diagnosis of
viral meningitis. Diagnostic accuracy is improved,
and time to diagnosis is shortened compared with
cultures, therefore reducing unnecessary days of
hospitalization, intravenous antibiotic therapy, and
additional diagnostic testing. 51-56
The absence of a positive Gram stain does not
exclude bacterial meningitis because it depends on
the number of organisms present and the use of
cytocentrifugation, yet it is positive in 90% of
patients with pneumococcal meningitis 57 and 80%
of those with meningococcal meningitis. 58 For
Listeria and gram-negative bacilli, the Gram stain is
positive in one third to one half of the samples. 59,60
The isolation of the bacterial pathogen confirms the
diagnosis for bacterial meningitis. The PCR of CSF is
most helpful in meningococcal disease in patients
with negative cultures. 61
The use of prior antibiotics, in particular oral, has
minimal effects on CSF cytology, but it may affect
the chemistry results. Cerebrospinal fluid glucose
and protein levels should be interpreted with
caution in the setting of antibiotic pretreatment.
The culture and Gram stain are more commonly
affected by prior use of antibiotics. 62,63
Table 6 reflects a previously validated score by
Nigrovic et al, 64 the Bacterial Meningitis Score. This
score is a clinical prediction rule for use in otherwise
healthy children older than 2 months with CSF
pleocytosis (WBC count N 10 cells/L) and no prior
use of antibiotics. It should be used in combination
152 VOL. 14, NO. 2 MENINGITIS IN CHILDREN / RICHARD AND LEPE

pathogens. One should err on the side of early

TABLE 6. Bacterial Meningitis Score (BMS). antibiotic administration rather than later.
Delays in administering antibiotics have been
Predictor Criteria (Points) associated with worse patient outcomes. 68-71 Eventu-
ally, antibiotics should be adjusted, depending on the
CSF Gram stain Positive (2 points if present,
0 if absent)
CSF total protein 80 mg/dL (1 point if present, TABLE 7. Suggested antibiotic dosing and
0 if absent) administration.
CSF ANC 1000 cells/mm 3
(1 point if present, 0 if absent) Outpatient or emergency center empirical therapy (IM/IV)
Peripheral ANC 10 000 cells/mm 3 Ceftriaxone Infants aged N 28 d: 100 mg/kg
(1 point if present, 0 if absent) sodium per dose once a day or divided every 12 h
Seizures During or before presentation Empirical parenteral therapy (IV)
(1 point if present, 0 if absent) Ampicillin Neonates
Aged b 7 d: 150 mg/kg per
A BMS of 2 or higher indicates bacterial meningitis with dose every 12 h
100% sensitivity and 97% specificity. A BMS of 0 predicted Aged N 7 d: 75 mg/kg per
aseptic meningitis with 73% sensitivity and 100% sensitivity. dose every 6 h
BMS indicates Bacterial Meningitis Score, ANC indicates Treatment for 48 h, neonates
absolute neutrophil count, CSF indicates cerebrospinal fluid. No meningitis: 75 mg/kg per
Data from: Nigrovic et al.64 dose every 12 h
Meningitis or no LP performed:
with clinical judgment to detect children at very low 75 mg/kg per dose every 6 h
risk for bacterial meningitis. Infants aged N 28 d
No meningitis: 50 mg/kg per
dose every 6 h
Treatment Meningitis or no LP performed:
Once the question of whether the clinical picture 100 mg/kg per dose every 6 h
favors bacterial vs viral/aseptic meningitis is an- Cefotaxime Neonates
swered, the course of treatment can be determined. sodium Aged b 7 d: 50 mg/kg per
A clinical picture of less specific signs/symptoms plus dose every 12 h
negative CSF criteria is sufficient evidence to allow Aged 7-28 d: 50 mg/kg per
the physician to cease antibiotic treatment and dose every 8 h
consider CSF PCR to verify a viral etiology. Reverse Infants aged N 28 d:
transcriptase PCR is now regarded as the criterion No meningitis: 75 mg/kg per
dose every 8 h
standard to diagnose viral meningitis; this is probably
Meningitis or no LP performed:
explained by the near-dominance of viral etiologies 75 mg/kg per dose every 6 h
for most cases of meningitis in children. 20 It is Gentamicin sulfate Neonates: 4 mg/kg per dose every 12 h
perhaps most valuable for serving as an indicator as Infants aged N 28 d: 2.5 mg/kg
to when to stop antibiotic treatment and when to per dose every 8 h
adjust for either a course of acyclovir or just Treatment of choice of suspected staphylococcus
supportive therapy until viral meningitis runs its Vancomycin Neonates
course. 65 If CSF pleocytosis is minimal but the Aged 7 d: 15 mg/kg per dose
patient exhibits specific clinical features of HSV every 12 h
meningitis, acyclovir should be initiated immediately Aged N 7 d: 15 mg/kg per dose
and PCR should be done for HSV as soon as possible. 20 every 8 h
Infants aged N 28 d
Herpes simplex virus is presently the only viral
No meningitis: 15 mg/kg per
meningitis for which acyclovir is recommended; dose every 8 h
other forms of viral meningitis usually run a mild Meningitis or no LP performed:
course and require no specific treatment. 66 15 mg/kg per dose every 6 h
If the diagnosis of bacterial meningitis is established Treatment of choice for HSV
or suspected, empirical antibiotic treatment should be Acyclovir Neonates and infants
initiated immediately following the guidelines out- 20 mg/kg per dose every 8 h
lined in Tables 7 and 8. 7,67 Empiric antibiotics should
be directed toward the patient's age because there is a IM indicates intramuscular, HSV indicated herpes simplex
correlation between age and most probable bacterial virus, LP indicates lumbar puncture.
 MENINGITIS IN CHILDREN / RICHARD AND LEPE VOL. 14, NO. 2 153

TABLE 8. Etiology and treatment of bacterial meningitis.

Patient Group Common Organisms Antimicrobial Therapy

0-28 d GBS, Escherichia coli, Listeria monocytogenes, Third-generation cephalosporin plus

and other gram-negative bacteria an aminoglycoside
1 and b 3 mo GBS, gram-negative bacilli, S pneumoniae, N meningitidis Third-generation cephalosporin
3 mo and b 3 y S pneumoniae, N meningitidis, GBS, gram-negative bacilli Third-generation cephalosporin
3 and b19 y S pneumoniae, N meningitidis Third-generation cephalosporin
Neurosurgical problems and S aureus, S pneumoniae Vancomycin + third-generation
head trauma cephalosporin

For resistant S pneumoniae, the American Academy of Pediatrics recommends vancomycin plus cefotaxime or ceftriaxone
as empiric therapy. It should also be used in any sick patients or patients with clear bacterial meningitis until sensitivities
and specificities of culture are completed.
Some data were from Sez-Llorens X, McCracken GH Jr. Antimicrobial and anti-inflammatory treatment of bacterial
meningitis. Infect. Dis. Clin. North Am. 1999 Sep;13(3):619636, vii 57; and 2013 Up to Date, Evaluation and management of
fever in the neonate and young infant (less than three months of age) and TCH Evidence-Based Outcomes Center Clinical
Algorithm for Neonates & Infants with Fever Without Localizing Signs (FWLS) (0-60 days). Evidence-Based Outcomes
Center, Quality and Outcomes Center. Texas Childrens Hospital; 2009. Plus additional data from other sources. 5863

specific CSF culture and sensitivity analysis, 20 but the
initial management should be aggressive to include
coverage for resistant pneumococcal meningitis (grade
1A recommendation) with cefotaxime (300 mg/kg/d, to
a maximum of 12 g divided into 3 doses) or ceftriaxone
(100 mg/kg/d, to a maximum of 4 g divided into 2
doses) plus vancomycin (50 mg/kg/d intravenously
[IV]; to a maximum of 4 g divided in to 4 doses).
Acyclovir should be given when a neonate is ill
appearing, if there is history of maternal genital herpes
and/or the presence of mucocutaneous vesicles, if the
child presents with seizures or focal neurologic
abnormalities, or if hepatic enzyme levels are elevated.
If a traumatic tap is suspected, one must be conserva-
tive in making the decision to start acyclovir, especially
if the infant is seriously ill. The dose of acyclovir is
60 mg/kg/d in 3 divided doses and continued until the
result of CSF culture or CSF HSV DNA PCR is negative.
An algorithm for patients older than 1 month has
been modified for this review (Figure 1). Resuscitation
should be a priority when indicated. Laboratory
evaluation should include a complete blood count
with platelets and differential, blood cultures, and
serum electrolytes with glucose, blood urea nitrogen,
and creatinine. In patients with clinical sepsis,
petechiae or purpura, prothrombin time and partial
thromboplastin time, and other markers of sepsis or
disseminated intravascular coagulation should be
obtained. If imaging is required on clinical grounds,
treatment including antibiotic therapy should not be
delayed; imaging should be obtained as soon as
reasonably possible.
The use of dexamethasone reduces the risk of
hearing loss in children with Hib meningitis, but there
is no clear evidence that it alters other neurologic
outcomes in children with bacterial meningitis. 72,73
The debate among experts continues in relation to the
efficiency of dexamethasone for children with menin-
gitis caused by other organisms. The American
Academy of Pediatrics Committee of Infectious
Diseases suggests that this therapy is beneficial in
children with Hib meningitis, if given before or at the
same time as the first dose of antimicrobial therapy.
The use of this agent after 1 hour of the administration
of the first dose of antibiotic does not improve the
outcome. Dexamethasone should not be used in
infants younger than 6 weeks or those with congenital
abnormalities of the central nervous system. 72,73
Treatment for special circumstances such as immu-
nodeficiency, recent neurosurgery, anatomical de-
fects, penetrating head trauma, CSF leak, and
epidemics requires consultation with an expert in
infectious disease and is beyond the scope of this
review. N meningitidis is best treated with penicillin, but
a third-generation cephalosporin or chloramphenicol
can be considered in patients allergic to -lactams. 74,75
In the referenced Red Book from the American
Academy of Pediatrics, alternative antibiotics per
etiology can be found, including the use of naficilin
or oxacillin for methicillin-sensitive Staphylococcus
aureus. Treatment should be adjusted upon availability
of cultures.
SUMMARY
Meningitis is an acute illness with signs and
symptoms of meningeal irritation. The manifesta-
tions of viral and bacterial meningitis can be similar,
154 VOL. 14, NO. 2 MENINGITIS IN CHILDREN / RICHARD AND LEPE
Figure 1. Management algorithm for infants ( 1 month) and children with suspected bacterial meningitis. Data from: Tunkel et al 73 and
Fleisher. 43
but the severity of viral etiologies is usually less. As
detailed previously, no signs or symptoms are
pathognomonic, and the clinician should be very
careful to avoid missing the diagnosis. Neonates often
present with vague and nonspecific complaints.
Children who present with suspicion of meningitis
should be treated as bacterial meningitis until the
diagnosis can be excluded.
Bacterial meningitis is an emergency that should
be evaluated and treated promptly, and the man-
agement algorithm should be followed closely. The
evaluation of clotting factors is particularly indicated
when purpuric lesions or petechiae are noticed or
clinical sepsis is present. Antibiotics should never be
withheld when bacterial meningitis is suspected, and
the LP cannot be performed or must be delayed.
The isolation of bacterial pathogen or a positive
PCR finding in the CSF confirms the diagnosis of
either viral or bacterial meningitis. In enterovirus
season (late summer/early fall), clinical findings and
 MENINGITIS IN CHILDREN / RICHARD AND LEPE VOL. 14, NO. 2 155
epidemiology can aid in the diagnosis, as with other
viral syndromes.
Beyond the neonatal period, S pneumoniae and N
meningitidis are the most common causes of bacterial
meningitis; certain host factors may predispose to a
particular organism. Very sick patients with selected
features such as immunosuppression and prior use
of antibiotics or history of exposures (ticks, tuber-
culosis, etc) should be approached accordingly.
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