Pediatric emergency medicine trisk 568

TABLE 94.7
EMPIRIC ANTIBIOTIC THERAPY FOR SUSPECTED ACUTE BACTERIAL MENINGITIS
Age

Most common pathogens

Empiric antibiotics

<1 mo

Group B streptococcus (S. agalactiae), E. coli,
Listeria monocytogenes, Klebsiella species

Ampicillin (50 mg/kg every 8 hrs in the first week
of life; 50 mg/kg every 6 hrs on days 8–28)
and
Cefotaxime (50 mg/kg every 8 hrs in the first
week of life; 50 mg/kg every 6 hrs on days 8–
28)

1–23 mo

S. pneumoniae, N. meningitidis, group B
streptococcus, E. coli, H. influenzae type b

Vancomycin (15 mg/kg every 6 hrs)
and
Cefotaxime (75 mg/kg every 6 hrs, maximum 2
g/dose) or ceftriaxone (50 mg/kg every 12 hrs,
maximum 2 g/dose)

≥24 mo

N. meningitidis, S. pneumoniae

Vancomycin (15 mg/kg every 6 hrs)
and
Cefotaxime (75 mg/kg every 6 hrs, maximum 2
g/dose) or ceftriaxone (50 mg/kg every 12 hrs,
maximum 2 g/dose)

From Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267–1284, by
permission of the Oxford University Press.

TABLE 94.8
MANIFESTATIONS OF NEONATAL HERPES SIMPLEX VIRUS INFECTION a

Goals of Treatment
The goal of treatment of neonatal HSV is the rapid recognition and initiation of acyclovir promptly. Clinical
outcomes include time to antiviral therapy and neurologic sequelae.
Clinical Considerations
Clinical recognition: There are three manifestations of HSV in the neonatal period: SEM disease, seen in
approximately 45% of cases; CNS disease, seen in 30%; and disseminated disease, seen in 25%. The most
common clinical and laboratory presentations are described in Table 94.8 . There is substantial overlap between
the three most common disease entities, as many children with vesicles have more invasive disease, and many
children with disseminated disease have CNS involvement. Children with isolated SEM disease have the best
prognosis, with few reported cases of death or neurologic sequelae. While the mortality rate for CNS disease is
low, most children have neurologic sequelae. In contrast to older patients, in whom HSV has a tropism for the
temporal lobes, neonatal CNS HSV infection often involves multiple portions of the brain. Children with
disseminated disease present septic, and require multiorgan system support, as they often have severe synthetic
hepatic dysfunction resulting in coagulopathy and can develop HSV pneumonitis, which is often hemorrhagic.

Adrenal involvement is common; as such, the provider should consider hydrocortisone for children with suspected


HSV disease. The most severe disease typically occurs in children who never develop a vesicular rash, as the
diagnosis often is delayed in these children. As such, the absence of a rash should not lead the clinician to
eliminate HSV from the differential diagnosis.
Triage considerations: Febrile and hypothermic neonates should be evaluated promptly for HSV in addition to
bacterial infections. The clinician’s index of suspicion for HSV should be increased in the following
circumstances: vesicles; seizures or abnormal neurologic examination; CSF pleocytosis; or evidence of hepatic
dysfunction, including coagulopathy.
Clinical assessment: The diagnosis is confirmed by isolation of HSV via culture or polymerase chain reaction
(PCR). Surface cultures should be obtained from the conjunctivae, nose, mouth, and anus (even if there are no
obvious vesicles in these locations), in addition to cultures being obtained from vesicles. In the latter instance, the
swabs should be rubbed against the base of the vesicle, as opposed to aspirating fluid from the vesicle itself. HSV
PCR of the CSF is more sensitive (97% to 100%) than viral culture of the CSF, but the sensitivity is lower early in
the disease process. As such, a negative HSV CSF PCR does not rule out CNS involvement. If the index of
suspicion for HSV disease is high, it is reasonable to repeat PCR testing prior to stopping therapy. PCR (qualitative
or quantitative) can also be obtained from the blood; this is of particular utility in children who are coagulopathic
or have other clinical features which make LP difficult. HSV serologies are not useful in the acute setting. In
addition to routine laboratory evaluation and cultures, ALT, prothrombin time, and partial thromboplastin time
should be obtained. Obtaining a serum glucose is also useful, as hepatic dysfunction can result in an inability to
mobilize glycogen stores and result in hypoglycemia.
Management: Neonates with suspected HSV should receive parenteral acyclovir (20 mg/kg every 8 hours).
Children in whom ocular disease is present should be promptly evaluated by an ophthalmologist and receive
topical antiviral therapy, such as 1% trifluridine (one drop every 6 hours) to the affected eye(s), in addition to
parenteral acyclovir. Neonates, especially those with disseminated disease, are likely to require blood products and
fresh frozen plasma to treat coagulopathy. Many of the considerations noted in the section on bacterial meningitis
also are applicable for HSV meningoencephalitis. Standard and contact precautions (if vesicles are present) should
be used for children with suspected HSV disease.

Meningitis, Aseptic
Both infectious and noninfectious processes can produce aseptic meningitis ( Table 94.9 ). The most common
cause is viral meningitis. In Lyme-endemic regions, clinicians should also suspect Borrelia burgdorferi as a cause
of aseptic meningitis. The signs and symptoms of aseptic meningitis mimic those of acute bacterial meningitis, but
alterations in level of consciousness or focal neurologic deficits are rarer than in bacterial meningitis. Initial
laboratory evaluation should parallel that described for bacterial meningitis. Enteroviral PCR should be sent on the
initial CSF. Ill-appearing children or infants in the first 1 to 2 months of life should have HSV PCR on the CSF
and serum sent as well (see HSV meningoencephalitis section) and acyclovir (20 mg/kg every 8 hours for children
0 to 3 months; 15 mg/kg every 8 hours for children >3 months of age) should be initiated. Most patients need no
further tests, but in atypical situations, consideration should always be given to nonviral causes that may mandate
additional diagnostic steps or specific therapy. If tuberculosis is suspected based on family contacts, high CSF
protein, a low CSF glucose with lymphocytic predominance, or abnormal chest radiography, then a Mantoux
tuberculin skin test (TST), and an interferon gamma release assay should be obtained. In endemic areas, serologic
studies for Lyme disease and antibiotic therapy may be indicated based upon the exposure history and time of year.
A CT scan provides essential information about patients with symptoms or signs of parameningeal infection, HSV
encephalitis, or CNS tumors and hemorrhages. Immunosuppressed patients develop infections with a wide variety
of unusual bacteria, fungi, and parasites that can be identified in many cases with appropriate examination and
culture of the CSF (e.g., India ink and acid-fast stains, cryptococcal antigen testing, fungal and mycobacterial
cultures).


TABLE 94.9
CAUSES OF ASEPTIC MENINGITIS
Viral

Enteroviral
Herpes simplex virus
Arboviral
Lymphocytic choriomeningitis virus
Mumps

Other viral infections

Bacterial

Early or partially treated bacterial meningitis
Parameningeal infection
Mycobacterium tuberculosis
Borrelia burgdorferi (Lyme disease)
Rickettsial diseases
Bartonella henselae (cat scratch)
Leptospirosis
Treponema pallidum (syphilis)
Mycoplasma

Fungal

Cryptococcus
Histoplasmosis

Parasitic

Candida
Naegleria
Toxoplasmosis
Taenia solium (neurocysticercosis)
Malaria
Trichinosis

Noninfectious

Neoplasia
Kawasaki disease
Hemorrhage
Collage vascular diseases
Hypersensitivity reactions
Heavy metal poisoning
Sarcoidosis

Because the CSF findings in aseptic meningitis overlap those in bacterial infections, hospital admission is
usually warranted until the CSF culture results are available. However, the experienced clinician may choose to
follow the older child as an outpatient if the family is reliable and nonviral causes (e.g., Lyme disease,
tuberculosis, cryptococcosis) are clinically unlikely. To guide clinicians, the Bacterial Meningitis Score has been
derived and validated to identify children at very low risk (negative predictive value 99.7%) for bacterial
meningitis. Low-risk features are negative CSF Gram stain; CSF absolute neutrophil count (ANC) <1,000 cells/
μL, CSF protein <80 mg/dL, peripheral ANC <10,000 cells/mm3, and no seizures at or prior to presentation.
Additionally, a positive rapid enteroviral PCR may support outpatient management if available and the patient is
clinically well.

Encephalitis and Meningoencephalitis


Encephalitis is an inflammation of the brain that can occur with or without associated meningeal irritation; the
former is termed meningoencephalitis, but the terms will be used interchangeably in this section. The clinical
manifestations can overlap with those of meningitis. The etiologies most commonly associated with encephalitis
are listed in
e-Table 94.2 ; however, an etiology is found in only a small fraction of children and adults with
encephalitis. In circumstances where etiologies are found, almost 70% are viral (most commonly enterovirus,
followed by HSV and Epstein–Barr virus [EBV]) and approximately 20% are bacterial. In the last two decades, it
has been recognized that several arboviruses endemic in the United States can cause encephalitis. These viruses,
which include West Nile, St. Louis, La Crosse, and the equine encephalitides, are termed arbo viruses because they

are ar thropod-bo rne viruses, not because they share phylogenetic characteristics. The clinical manifestations
include altered consciousness or behavioral changes, seizures, hemiparesis, or ataxia, often with nausea and
vomiting. Fever is not uniformly present. Postinfectious cases can have associated demyelination in the absence of
acute signs of infection; most cases of brainstem encephalitis are postinfectious. The differential diagnosis of
encephalitis includes ingestion, metabolic disorders, structural lesions (masses, bleeds, emboli), acute
demyelinating encephalomyelitis (ADEM), and autoimmune encephalitis (NMDAR). One diagnostic approach to
the child with suspected encephalitis is listed in Table 94.10 , realizing that repeated history taking may be
necessary to elucidate all exposures a child may have had. Children with encephalitis should be started on
acyclovir (20 mg/kg every 8 hours) pending HSV PCR, as this is one of the few treatable causes of encephalitis. If
a CSF pleocytosis exists, empiric initiation of parenteral antibiotics (e.g., vancomycin [15 mg/kg every 6 hours]
and cefotaxime [75 mg/kg every 6 hours; maximum: 2 g/dose]) is reasonable pending bacterial culture results.
Consideration should be given to admission of these patients to intensive care unit settings for closer monitoring
given concerns for changes in the ability to protect the airway, increased intracranial pressure, or electrolyte
imbalances. Standard precautions are recommended for most forms of encephalitis.