Pediatric Meningitis: Clinical Guidelines, Issues, and Update
Author: Charles A. Nozicka, DO, FAAP, Assistant Professor of Pediatrics, Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, WI; Medical Director of Pediatric Services, Columbia Hoffman Estates Medical Center, Hoffman Estates, IL.
Peer Reviewer: Robert Schafermeyer, MD, Associate Chairman, Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC.
The diagnosis of pediatric meningitis presents the emergency physician with significant clinical challenges and formidable medicolegal risks. Young children and infants with meningitis are notorious for presenting with subtle symptoms and signs, often mimicking other more common illnesses. Although much has been published in the last several years regarding the approach to the febrile infant and child and the treatment of pediatric meningitis, clinicians must continue to approach every febrile child as potentially having bacterial meningitis. There remains the necessity for emergency physicians to continually update their practices and remain current in the diagnosis and treatment of this disease.
Pediatric meningitis continues to be a high-risk diagnosis for clinicians. It is often difficult to diagnose in its early stages and has the potential for serious permanent morbidity and death. Associated lawsuits can take the emergency physician beyond the limits of a malpractice policy, as judgments can be in the millions of dollars. Not only must the diagnosis be suspected and made in a timely matter, but these complicated cases demand exquisite attention to detail in all aspects of care.
Emergency physicians can improve the outcomes of children by suspecting the disease early and initiating treatment promptly. But which signs and symptoms are most useful in identifying the febrile infant or child that has early meningitis? Is there a point on the continuum from occult bacteremia to meningeal seeding to early meningitis when the diagnosis is impossible to make?
Which child with a febrile seizure needs a lumbar puncture? Is dexamethasone indicated in any child with suspected meningitis? Is there a "gold standard" pertaining to the timing of antibiotics after a child with meningitis presents to the ED?
This article addresses these questions and others associated with the latest standards for the diagnosis and treatment of pediatric meningitis. Its recommendations are based on available data; controversies are discussed where they currently exist.
The Editor
Initiation of Infection
Meningitis is characterized by inflammation of the meninges, connective tissue structures that surround the brain and spinal cord. When pathogens invade the central nervous system, they do so by several potential mechanisms. These include hematogenous dissemination after bacterial colonization and direct spread from a distant focus of infection, such as the mastoid ear cells or paranasal sinuses. In order to invade the nervous system, pathogenic organisms must penetrate the continuous protective cell layer of the blood brain barrier. Any disruption of this normal anatomy by trauma, operative procedures, or congenital deformities may facilitate such penetration. initiating infection.1
In cases involving hematogenous dissemination, the child initially has colonization of the nasal pharynx. The organism may then spread into the blood stream via the surrounding mucous membranes and capillaries. If the infecting organism is of sufficient virulence or inoculation, a significant bacteremia ensues which results in eventual meningeal invasion and bacterial replication in the subarachnoid space. The development of a sustained, high-grade bacteremia has been suggested as one important factor in the development of central nervous system invasion. Several investigators have suggested that the treatment of occult bacteremia in the young child or infant with initial empiric intervention during the bacteremic stage may prevent serious bacterial infections such as bacterial meningitis.2
Numerous investigators have studied the inflammatory response caused by the penetration of organisms into the central nervous system. Acute inflammatory mediators such as interleukins and cytokines have been implicated in the pathophysiology. This increased inflammatory response after initial antibiotic administration may result in hearing loss and other neurological sequelae; and is the theoretical basis for the use of steroids early in bacterial meningitis.3 Other various inflammatory mediators, such as superoxides and tissue necrosis factor (TNF), are the subject of numerous recent investigations.4,5
Acute Bacterial Meningitis
The bacterial organisms causing acute meningitis in the pediatric age group vary according to the underlying health status and age of the patient. In immunocompetent children, older than 3 months of age, three bacterial species account for the majority of CNS infections: Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis.6 Over the past five years, the widespread use of H. influenzae type B (HiB) conjugate vaccines has decreased the incidents of HiB meningitis in developed countries significantly.7,8 Between 1987 and 1994, the incidence of HiB meningitis declined 95% in the United States.8
Unique organisms such as group B Streptococcus, Escherichia coli, and Listeria monocytogenes, resulting from the infant’s contact with the perineum during the birth process, cause infection in the neonatal period (0-1 month). 9 Table 1 notes the most common organisms causing meningitis in each age group. Nevertheless, it is important to note that these age groups overlap. Salmonella meningitis, usually associated with gastroenteritis, is an uncommon cause of acute meningitis in the infant less than 12 months of age.1 Children with cerebral spinal shunts are susceptible not only to the usual pediatric pathogens, but may also be infected with Staphylococcus species.10 The most commonly cultured organisms in children with these shunts are Staphylococcus epidermidis and S. aureus.10 S. epidermidis may cause meningitis and sepsis in premature infants.
Clinical Presentation
The clinical presentation of acute bacterial meningitis differs significantly with the age of the child. Older children and adolescents frequently present with headache, fever, altered sensorium, and meningismus. Kernig’s or Brudzinski’s signs may be absent in up to 50% of adolescents and adults with bacterial meningitis.1 Their absence does not rule out the diagnosis. Vomiting is seen in more than half the patients presenting in this older age group.1 Younger pediatric patients may not manifest many of these classic symptoms and signs of bacterial meningitis.1 Neonates with acute bacterial meningitis often lack meningismus. Clinical clues of meningitis in neonates are temperature instability (hyperthermia or hypothermia), poor feeding, listlessness, lethargy, irritability, vomiting, or respiratory distress. A change in the child’s usual feeding pattern or state of alertness may be an important sign of meningitis. However, these findings are non-specific in the neonate and may be associated with numerous other acute illnesses. A bulging fontanelle may be seen in up to one-third of cases, although it usually appears later in the course of illness.1
Suspecting the Diagnosis
Meningitis, especially in children less than 2 years old, is frequently associated with acute otitis media, pneumonia, and even gastroenteritis. Therefore, the emergency physician must have a low threshold in considering the diagnosis of bacterial meningitis even with these other primary diagnoses. Although febrile children account for approximately 20% of all visits to the ED,11 it is not necessary to perform a lumbar puncture (LP) in every acutely febrile child with non-specific findings. The most important consideration in suspecting acute bacterial meningitis in the young child or infant is his or her perceived interaction with the surrounding environment. The child who is difficult to console by his or her mother or is paradoxically irritable (increasingly agitated with parental comforting) should be suspect. LP is recommended in the young child or infant who fails to follow your examination, interacts appropriately during a short period of observation, or appears more toxic than usual with an acute febrile illness. Again, the finding of another bacterial focus during the work-up of the young child or infant does not rule out meningitis.
All febrile neonates less than 2 months of age should undergo the full septic work-up, usually with initiation of empiric antibiotic treatment.12-14 This "work-up" includes bacterial cultures of urine, blood, and CSF.12-14 The difficulty in assessing the febrile neonate still mandates this aggressive laboratory evaluation.11-14
The age group of greatest concern for the practicing emergency physician is the child between the ages of 2 and 24 months. In these younger children, the initial presentation of early meningitis is often non-focal with fever, relative lethargy, irritability, and/or vomiting. Several investigators have studied the frequency of positive meningeal signs in young infants. Samson et al identified 21 infants ages 1-15 months with bacterial meningitis and found only 48% had positive meningeal signs, including nuchal rigidity or Kernig’s or Brudzinski’s signs.14 Walsh-Kelly et al found nuchal rigidity in only 27% of infants aged 0-6 months with bacterial meningitis compared to 95% of patients aged 19 months or older.15 The same investigators found that 28% of infants 12 months of age and younger with bacterial meningitis did not have physical evidence of meningeal irritation.15 A high index of suspicion for early bacterial meningitis is essential when evaluating the febrile infant 12 months of age or younger.
The "Partially Treated" Child
A child with partially treated meningitis may present atypically.7 Pretreatment with oral or inadequate parenteral antibiotics may "blunt" the severity of symptoms and signs. Children with partially treated meningitis demonstrate lower average maximum temperatures, more subtle alterations in mental status, and, often, a longer duration of symptoms prior to diagnosis.7 The emergency physician must be cognizant of the often subtle presentations of young children and infants who are partially treated.
The Child with a Cerebrospinal Shunt
The clinician will frequently evaluate a child with a cerebrospinal shunt. The most common of these are ventriculoperitoneal (VP) shunts. These patients are at risk not only for the usual bacterial pathogens, but are also at risk for staphylococcal meningitis. Their presentations are often similar to a "partially treated" child, with more subtle and non-specific symptoms and signs.16
The ventricular catheter is attached subcutaneously to a reservoir that may be percutaneously tapped to obtain ventricular fluid for both diagnostic and therapeutic purposes.17 It is recommended that the emergency physician obtain neurosurgical consultation prior to tapping a shunt reservoir.17
The Lumbar Puncture
Analysis of CSF, usually obtained by LP, is the basis for evaluation of the patient with suspected meningitis. In children without evidence of increased intracranial pressure, focal neurological findings, or papilledema, a CT scan is not necessary prior to an LP; it is extremely unlikely that uncal herniation with develop without evidence of increased intracranial pressure on physical examination. 18,19
With suspected increased intracranial pressure, a blood culture is obtained and empiric antimicrobial therapy initiated while the CT scan is pending.1,19 This same approach is usually required for patients with HIV, a history of brain tumors or neoplasms, or in whom a brain abscess is suspected from history and physical examination usually require this approach. Although one recent literature search found no evidence of a patient herniating with acute bacterial meningitis as a result of an LP,19 cerebral herniation occurring after LP in children with a normal CT scan has been reported.20
Once obtained, CSF should be sent for cell count, protein, glucose, bacterial culture, and Gram’s stain. Opening pressures, helpful in older children and adults, are usually not obtained in the infant age group.
A CSF glucose level of less than 40 mg/dL or a CSF glucose-to-blood glucose ratio of less than 0.3 to 0.5 suggests bacterial meningeal infection, as does a CSF protein of more than 150-170 mg/dL in neonates or 40-50 mg/dL in older infants and children.17 Children with significant hypoglycorrhachia (CSF glucose < 20 mg/dL) have a poorer prognosis than those with normal CSF glucose. In HIV-positive children, India ink, cryptococcal antigen, acid fast bacillus (AFB) smear and culture, and fungal cultures are included. Children with history of tuberculosis exposure or travel to an area endemic for tuberculosis should have CSF AFB smear and culture. These tests may not be included in the usual CSF panels in many institutions and must be specifically ordered. Table 2 delineates the usual cerebrospinal fluid characteristics of children. Initial CSF analysis may be unreliable in differentiating aseptic from bacterial meningitis. Finally, infants in the first month of life may have higher baseline WBC counts and protein than older children and adults.
Children with ventriculoperitoneal shunts will have elevated baseline CSF protein and cell counts; however, approximately 90% of those with cell counts greater than 100 cells/mm3 will be infected.16 Although higher WBC counts (generally > 1000 cell/mm3) with a predominance of polymorphic neutrophils (PMNs) are associated with bacterial meningitis, a finding of fewer WBCs (or < 50% PMNs) may be seen with early bacterial disease. Several investigators have reported series of patients with essentially normal CSF that were subsequently diagnosed with acute bacterial meningitis.21,22 Most of the patients in these two studies were less than 2 years of age. These studies indicate that a small number of patients with acute bacterial meningitis may present to a clinician during the early phase of meningeal invasion and have apparently normal CSF indices. Likewise, in early bacterial meningitis, a relatively low WBC cytology, negative Gram’s stain and even latex agglutination may mimic a child with aseptic meningitis. A child who clinically appears ill even with normal spinal fluid analysis or the consideration of early sepsis or meningitis mandates immediate empiric antimicrobial therapy and hospital admission. Such is often the case with early meningococcemia without meningitis. In the child admitted as "sepsis" with a "viral-appearing" CSF, repeat LP 12-24 hours later may clarify the situation with a conversion to CSF indices consistent with bacterial infection. Clinicians must be very cautious in making a diagnosis of aseptic meningitis based on initial CSF characteristics and electing not to treat with antibiotics.
The Traumatic LP
Traumatic spinal punctures may create a diagnostic challenge. The "traumatic tap" usually will "clear," producing less RBCs in the last sample tube compared to the first, whereas a subarachnoid hemorrhage results in an equal number of RBCs in each sample. The number of WBCs expected in a sample after a traumatic tap may be estimated.23 This formula estimates:
# of WBCs introduced/mm3 = (peripheral WBC) ´ (CSF RBCs)
(peripheral RBCs)
The expected WBC count is compared to the actual CSF WBC result. Another estimate is that for each 1000 RBCs introduced traumatically, 1-2 WBCs will be introduced.23
Associated Diagnostic Work-up
Other chemistry and hematological tests are usually obtained in the ED to help facilitate the management of the patient. A CBC is traditionally part of the patients work-up for sepsis, significant bacterial illness, or meningitis in the pediatric patient. A normal WBC count with the absence of a left shift does not exclude a significant bacterial infection and cannot be used to exclude bacterial meningitis. Serum electrolytes and glucose are obtained as a baseline and to exclude the syndrome of inappropriate antidiuretic hormone (SIADH).
Bacterial antigen tests of CSF (latex agglutination and counter immunoelectrophoresis) often routinely ordered, are relatively expensive and are usually of little value in the acute phase of management. An exception is the child on antibiotics for another focus of infection who presents with partially treated meningitis. Although the CSF cytology usually will be abnormal, instances of falsely negative cultures and Gram’s stains have been reported in patients who present with meningitis previously treated with antibiotics.1,7,24,25 In these cases, the latex agglutination or other rapid antigen detection test may yield a diagnosis.26 A clinician must realize, however, that there are many false-positive and false-negative results associated with rapid antigen detection.26 Use of urine for CIE or latex agglutination has even less specificity when used to identify a bacterial organism in meningitis.26
Numerous other laboratory tests have been evaluated to increase the specificity and sensitivity in patients with acute meningitis. CSF limulus lysate, CSF lactate,27 and CSF leukocyte esterase have been studied to help differentiate between aseptic and bacterial meningitis,27 but they are rarely indicated over the routine CSF analysis.17 Blood cultures are obtained, along with CSF, to rule out sepsis or bacteremia and increase the diagnostic yield for a bacterial pathogen.
A Differential Diagnosis
Occult Bacteremia. The pathophysiology of hematogenous dissemination involves the initially asymptomatic child being colonized with a virulent bacterial pathogen. This colonization leads to hematogenous dissemination and an initially "occult" bacteremia. During the early bacteremic phase, the infant or child may have a paucity of non-specific clinical findings. As the pathogens spread from bacteremia to meningeal invasion, a subtle, non-specific presentation including fever, irritability, or vomiting may be the only clinical findings. During the early meningeal phase, the diagnosis may be elusive until more focal signs develop. Clinicians caring for acutely febrile children must be aware that in this early phase, clinical signs and symptoms may be subtle and preclude the diagnosis of bacterial meningitis. Obviously there is a clinical continuum in the development of meningeal irritation in which specific signs of meningitis may be completely absent in the infant with early meningitisthe diagnosis is essentially clinically impossible to make during this period. The clinician evaluating the acutely febrile child must explain these issues to parents and provide comprehensive written discharge instructions enabling the parents to follow up quickly if the clinical condition of the child deteriorates.
Sepsis. The same pathophysiology that accounts for the development of meningitis explains the development of sepsis. Colonization leads to occult bacteremia, which, in turn, may lead to dissemination of bacterial infection to distant foci or to overt clinical sepsis.31 In children with fever, cyanosis, hypothermia, altered mental status, or other non-specific significant clinical presentations, the lack of positive CSF findings does not rule out sepsis. Meningococcemia is an example of a rapidly developing sepsis syndrome that occurs without clinical meningitis, with the child developing sepsis, hypotension, and DIC within a period of only a few hours.31 The child who presents with significant irritability, altered mental status, or signs of hemodynamic instability mandates stabilization of the ABCs and empiric antibiotic treatment initiatedeven in light of a negative spinal tap.
Encephalitis. Encephalitis is an inflammation of the central nervous system, usually of viral etiology, that often mimics meningitis. Encephalitis causes direct inflammation of the brain parenchyma. Patients usually present with profound altered mental status, severe headache, vomiting, autonomic nervous system dysfunction, or ataxia.32,33 With the exception of HSV, no specific treatment is available for most cases. Herpes simplex virus type 2 (HSV-2) in adolescents, often seen in conjunction with genital HSV, is usually associated with a self-limited form of meningitis, although chronic symptoms and recurrent meningitis does occur.33 HSV infections in infants are usually caused by HSV-2, a complication of maternal genital infection.33 Newborn infants usually present within the first week of life with fever or temperature instability and, often, jaundice. Vomiting, lethargy, respiratory distress, cyanosis, and shock may follow shortly. The presence of vesicular lesions (typically on the presenting body part during delivery) is helpful in making the diagnosis. However, skin lesions may be absent in up to 20% of infants.33 Herpes simplex virus type 1 (HSV-1), may cause a rapidly progressive fatal encephalitis occurring in approximately three-fourths of untreated cases.33 Children or adolescents with HSV-1 encephalitis usually have an abrupt onset with fever, chills, headaches, conjunctivitis, myalgias, sore throat, and other non-specific symptoms. Inflammation may be localized to the frontal temporal area with focal findings simulating a mass lesion, or the inflammation may be diffuse, involving both cerebral hemispheres.
LP usually reveals CSF pleocytosis with a predominance of lymphocytes. The diagnosis is suggested by characteristic CSF findings and clinical presentation along with MRI findings suggestive of a characteristic frontal temporal lesion. A brain biopsy may be necessary for confirmation, because HSV is rarely cultured directly from the CSF.33
When skin lesions are present, viral antigens can be detected using immunofluorescence, immunoparoxidase, or ELISA techniques. The diagnosis is strongly suggested by characteristic temporal lobe discharges on EEG and by temporal lobe swelling on MRI. Treatment with acyclovir should be initiated early if clinical suspicion for HSV encephalitis is high.33
Viral Meningitis. Many other viruses are capable of causing encephalitis32,33 or meningitis. Enteroviruses and arboviruses are the most common etiologic agents. Measles, mumps, or varicella can cause a post-infectious encephalitis occurring several weeks after the initial illness.32 These infections, considered diagnoses of exclusion, may mimic bacterial meningitis or HSV encephalitis, diseases which have specific treatments. Likewise, in the immunocompromised or HIV-positive patient, Cryptococcus neoformans and tuberculosis meningitis are diagnostic considerations. Lyme disease may present as aseptic meningitis. It should be considered with suggestive historical or physical findings.34
Non-Infectious Considerations. Other diagnostic entities that present with altered mental status and fever are toxicological syndromes including salicylates, phencyclidine, and acute lead encephalopathy or rheumatological diseases such as systemic juvenile rheumatoid arthritis, systemic lupus erythematosis (SLE), and, occasionally, Kawasaki’s disease. Subarachnoid hemorrhage, although rare in the pediatric population, can produce signs of meningismus with altered mental status. Subarachnoid hemorrhage can usually be distinguished from bacterial meningitis by a sudden onset of severe headache, and lack of prodromal signs in the presence of crenated RBCs in the cerebral spinal fluid with a paucity of WBCs.
Management. The initial management of children suspected of having meningitis includes airway management, evaluation for hypoxia, dehydration, increased intracranial pressure, electrolyte abnormalities, and coagulopathies. Assessment for shock with attention to mental status changes, peripheral profusion, delayed capillary refill, and significant tachycardia with or without hypotension are priorities for the emergency physician. Treatment of shock requires initial boluses 20 cc/kg of normal saline or Ringer’s lactate. If more than 40 cc/kg is required, consider central venous pressure monitoring.17,35 Although fluid restriction has been advocated in the past to prevent SIADH, most experts advocate conservative fluid management. Once circulation stabilization is achieved, fluids should be continued at 75-100% of maintenance requirements for the first 24-48 hours.36
Antibiotics should be initiated immediately on suspicion of bacterial meningitis. Initial treatment decisions are empirical because culture results will not be available for at least 24 hours. A Gram’s stain of the CSF must be examined for organisms, but results should not be the sole basis for initiating empiric therapy. Other considerations in antibiotic selection are age, underlying chronic conditions, and the child’s immunologic status. If immediate LP cannot be performed because of cardiovascular instability, technical difficulties, or consideration for increased intracranial pressure, antibiotics should be initiated after obtaining a blood culture with the anticipation that the LP will be completed as early as possible.35 When bacterial meningitis is suspected and vascular access cannot be achieved quickly, the intramuscular administration of antibiotics in usual parenteral dosages is recommended.17,31 For the child in shock who needs immediate fluid resuscitation with antibiotics, intraosseous administration is appropriate.17,31 Table 3 summarizes appropriate medications for bacterial meningitis.
Treatment Issues
Does Antibiotic Administration Before LP Alter CSF Results? Many physicians are concerned that giving antibiotics before an LP will significantly interfere with CSF analysis and confuse the diagnosis. One study addressing this issue indicates that although the potential for false-negative CSF cultures exist, a combination of using Gram’s stains, latex agglutination or counter current immunoelectrophoresis (CIE), and pretreatment blood cultures usually yield the suspected pathogen.37 The initiation of antibiotics before an LP will rarely alter the CSF enough to interfere with appropriate interpretation. The emergency physician should not wait for LP (or CT) results before starting appropriate antibiotics.
Antibiotics Should Be Initiated Within 30 Minutes of Presentation to the ED. Classic teaching recommends treatment of acute bacterial meningitis with parenteral antibiotics within 30 minutes of patient presentation. Studies have not demonstrated better outcomes with earlier administration of antibiotics,38,39 and prospective studies designed to address this issue will never be done. Several investigations have demonstrated the average time to administration of antibiotics at 2.1-3.0 hours.40,41 This is in contrast to the often quoted "gold standard" of 30 minutes.41 One study attributed the majority of the delay to time after the initial physician encounter, which, thus, is potentially preventable.40 Theoretical considerations of treating bacterial meningitis mandate appropriate antibiotics without preventable delay; however, the frequently quoted "within 30 minutes" of presentation may be an unreasonable goal and probably does not represent the "gold" standard.41
Dexamethasone or Not? That is the Question. Administration of dexamethasone during the treatment of H. influenzae (HiB) meningitis reduces the incidence of subsequent sensorineural hearing loss.42-49 The proposed mechanism of action is inhibition of inflammatory mediators such as cytokine production in the CSF.47 Dexamethasone has recently been studied with other bacterial pathogens; the benefits and the potential disadvantages are controversial.42 Several clinical trials have claimed to support the use of dexamethasone in cases of children with pneumococcal meningitis.42-49 A recent prospective study of 56 children with pneumococcal meningitis demonstrated a significant reduction in neurologic sequelae (most notably hearing loss) in dexamethasone-treated patients.49 If cephalosporin-resistant pneumococcal meningitis is suspected, vancomycin is indicated in the initial antimicrobial regimen.34,50 A potential complication using dexamethasone with pneumococcal meningitis has recently been reported: The penetration of vancomycin across the inflamed meninges is maybe decreased with dexamethasone therapy, potentially decreasing drug concentrations in the CSF.50,51 This is because inflammation of the blood-brain barrier during acute meningitis facilitates vancomycin passage into the subarachnoid space.42 Since the penetration of rifampin to the CSF is not altered by dexamethasone therapy, some experts have suggested that initial therapy in areas with cephalosporin-resistant organisms consist of cefotaxime or ceftriaxone combined with rifampin. In those patients in whom meningitis may be caused by HSV, concomitant use of dexamethasone could potentially have adverse effects.
The preponderance of data appears to support the use of dexamethasone in children older than 3 months of age with bacterial meningitis.42-49 Caution is necessary if HSV or cephalosporin-resistant pneumococcal meningitis is a consideration.17,50 The recommend dosage of dexamethasone is 0.15 mg/kg q6h intravenously for the first four days of therapy.31,44,47 The therapeutic effect of dexamethasone is maximized if it is administered 10 minutes before the administration of the first dose of antibiotics.44,47 Recommendations for the use of dexamethasone with tuberculosis meningitis differ and are beyond the scope of this report.51
Complications
Hypoglycemia. Hypoglycemia may occur as a reaction to stress, poor feeding, or shock. It is most commonly concomitant with meningitis in the first three months of life.31 Any child with altered mental status should have a bedside blood glucose check. If it is below 50 mg/dL, 25% dextrose should be given at a dosage of 0.25-1.00 g/kg (1-4 cc/kg).31 In infants less than 1 month of age, using a bolus of 10% dextrose (5 cc/kg) is advisable. This should be followed by IV infusions containing 5% dextrose solutions. Occasionally 10% dextrose-containing solutions may be necessary to maintain acceptable serum glucose levels.
Seizures. Seizures may be seen in up to 25% of children with bacterial meningitis. They are occasionally seen with viral meningitis, and are common with encephalitis, especially HSV infection.
Seizures should be treated with lorazepam 0.05-0.1 mg/kg/dose IV or diazepam 0.1-0.2 mg/kg/dose IV q5-10min (maximum, 10 mg). Rectal diazepam should be considered if venous access cannot be quickly obtained. The intravenous preparation is administered rectally, via a feeding tube or a 1 mL TB syringe, in a dosage of 0.5 mg/kg/dose. If diazepam is used, a longer-acting anticonvulsant such as phenytoin should be initiated. Anatomical abnormalities, such as subdural effusion or cerebral abscesses, and metabolic derangements should be excluded.
Disposition. All pediatric patients with possible bacterial meningitis require hospitalization. Those at risk for associated sepsis with poor profusion, coma, seizures, purpura, or petechia require close monitoring in a pediatric intensive care unit. A patient in whom there is a suspicion for bacterial meningitis despite a CSF analysis appearing normal or consistent with viral meningitis should be admitted for IV antibiotics pending culture results in 48-72 hours. Traditional management is on an inpatient basis; completion of therapy on an outpatient basis may be an option in the near future in uncomplicated patients, thus reducing medical costs.53
Chemoprophylaxis. Chemoprophylaxis is indicated in household, day care, nursery school contacts, and anyone with close intimate exposure to oral secretions of patients with meningococcal meningitis.17,32,55 Household contacts of patients with H. influenzae meningitis should receive chemoprophylaxis if there is at least one child 4 years old or younger in the household;52 then all contacts in the household, including adults, children, and the patients themselves should receive chemoprophylaxis (usually rifampin), including individuals previously immunized.17,52 Clinicians must be aware that the dosages for rifampin prophylaxis differ between these two pathogens and that prophylaxis does not prevent disease in all cases. Fever in a susceptible contact of a child with bacterial meningitis should be promptly evaluated for possible early invasive disease, even if prophylaxis was given. Pregnant women should not take rifampin.52 Rifampin causes orange bodily fluids (urine, stool, tears) and may stain soft contact lenses. Chemoprophylaxis and rifampin dosages are summarized in Table 4.
Prevention. Immunization with H. influenzae conjugate vaccine is now routinely available to children beginning at 2 months of age. Children who are less than 2 years of age who have recovered from H. influenzae meningitis should receive the H. influenzae conjugate vaccine, as the disease does not provide consistent long-term protection against reinfection.17,52 A polyvalent meningococcal vaccine is available but is only recommended for children older than 2 years of age who are at high risk for infection (i.e., those with immunodeficiency syndromes or complement component deficiency). A pneumococcal polyvalent vaccine composed of capsular antigens from 23 serotypes is available. It is also only recommended for children who are older than 2 years of age who are at risk of developing pneumococcal disease (i.e., immunodeficiency syndromes, sickle cell disease, nephrotic syndrome, and recurrent meningitis after head trauma).
Summary
Physicians face many perplexing questions and dilemmas concerning the diagnosis and management of pediatric meningitis. There are a number of important points to bear in mind. First, bacterial meningitis may be difficult to diagnose in the initial stages, especially during the neonatal period; the younger the child, the more subtle the signs and symptoms. Next, children may present with CSF findings indicating a viral infection or within normal limits (rarely) and still have early bacterial meningitis. Importantly, a negative LP never "rules out" sepsis, and empiric antimicrobial therapy should never be delayed to obtain an LP if bacterial meningitis is suspected. In partially treated patients, blood culture and bacterial antigen tests can often identify the causative organism.
Third-generation cephalosporins, cefotaximine, and ceftriaxone are the drugs of choice for pediatric bacterial meningitis. In the neonate, cefotaxime is combined with ampicillin. When cephalosporin-resistant S. pneumoniae is suspected, vancomycin is added. Dexamethasone administered with or before initial antibiotics decreases the neurological sequelae of HiB meningitis; its routine use with other bacterial etiologies is controversial.
References
1. Tunkel AR, Scheld WM. Acute meningitis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone Inc.; 1995:831-865.
2. Singer JI, Vest J, Prints A. Occult bacteremia and septicemia in the febrile child younger than two years. Emerg Med Clin North Am 1995;2: 381-416.
3. Jafari HS, McCracken GH. Dexamethasone therapy in bacterial meningitis. Pediatr Ann 1995;2:82-88.
4. Arditi M, Ables L, Yogev R, et al. Cerebrospinal fluid tumor necrosis factor-M and platelet-activating factor concentrations and seventy of bacterial meningitis in children. J Infect Dis 1990;162:139-147.
5. Saez-Horens X, Ramilo O, Mustafa MM, et al. Molecular pathophysiology of bacterial meningitis: Current concepts and therapeutic implications. J Pediatr 1990;116:671-684.
6. Bohr V, Hansen B, Jessen O, et al. Eight hundred and seventy-five cases of bacterial meningitis; clinical data, prognosis and the role of specialized hospital departments. J Infect 1983;7:21-30.
7. Lipton JD, Schafermeyer RW. Evaluating concepts in pediatric bacterial meningitis: Part IPathophysiology and diagnosis. Ann Emerg Med 1993;22:1602-1615.
8. Progress toward elimination of Haemophilus influenzae type B disease among infants and children. United States 1987-1995. MMWR Morb Mortal Wkly Rep 1996;45:901-905.
9. DeLanois J. Acute bacterial meningitis in the newborn. J Antimicrob Chemother 1994;34:61-73.
10. Wiedermann BL. Characteristics of pathogenic microbes and infectious syndromes. In: Holbrook PR. Textbook of Pediatric Critical Care. Philadelphia: WB Saunders Co.; 1993:898-917.
11. Singer JI. Fever and sepsis. In: Reisdorff EJ, Roberts MR, Wegenstein JG, eds. Pediatric Emergency Medicine. Philadelphia: WB Saunders Co.; 1993:556-565.
12. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guidelines for the management of infants and children 0-36 months of age with fever without source. Pediatrics 1993;92:1-12.
13. Nozicka CA. Evaluation of the febrile infant less than 3 months of age with no source of infection: new management strategies. Am J Emerg Med 1995;13:315-318.
14. Samson JH, Apthorp J, Finely A. Febrile seizures and purulent meningitis. JAMA 1969;210:1918-1919.
15. Walsh-Kelly C, Nelson DB, Smith DS, et al. Clinical predictors of bacterial versus aseptic meningitis in childhood. Ann Emerg Med 1992;21: 910-914.
16. Odio C, McCraken GH, Nelson JD. CSF shunt infections in pediatrics. Am J Dis Child 1984;138:249-251.
17. Barkin RM. Bacterial Meningitis. In: Barkin RM, ed. Pediatric Emergency Medicine: Concepts and Clinical Practice. 2nd ed. St. Louis: Mosby-Yearbook, Inc.; 1996
18. Haslem RA. Role of computed tomography in the early management of bacterial meningitis. J Pediatr 1991;119:157-159.
19. Archer B. Computed tomography before lumbar puncture in acute meningitis: A review of the risks and benefits. Can Med Assoc J 1993;148:961-965.
20 Rennick G, Shann F, de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ 1993;306:953-955.
21. Omorato IM, Wormser GP, Nicholas P. "Normal" CSF in bacterial meningitis. JAMA 1980;244:1469-1471.
22. Levy DR. Lumbar puncture and the diagnosis of meningitis. South Med J 1981;74:28-30.
23. Bonadio WA, Smith DS, Goddard S, et al. Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture. J Infect Dis 1990;162:251-254.
24. David SD, Hill SR, Feigl P, et al. Partial antibiotic therapy in Haemophilus influenzae meningitis: its effect on cerebrospinal fluid abnormalities. Am J Dis Child 1975;129:802.
25. Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases, 3rd ed. Philadelphia: WB SaunderS; 1992.
26. Dougherty JM, Jones J. Cerebrospinal fluid culture and analysis. Ann Emerg Med 1986;15:317.
27. Nelson N, Eeg-Olofsson, Larsson L. The diagnostic and predictive value of cerebrospinal fluid lactate in children with meningitis; its relation to current diagnostic methods. Acta Paediatr Scand 1986;75:52-57.
28. Lieu TA, Schwartz JS, Jaffe DM, et al. Strategies for diagnosis and treatment of children at risk for occult bacteremia: Clinical effectiveness and cost-effectiveness. J Pediatr 1991;118:21-29.
29. Fleisher GR, Rosenberg N, Vinci R, et al. Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia. J Pediatr 1994;124:504-512.
30. Baker MD, Bell LM, Avner JR. Outpatient management without antibotics Fof fever in selected infants. N EngL J Med 1993;329:1437-1441.
31. Fleisher GR. Infectious disease emergencies. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 3rd ed. Baltimore: Williams and Wilkins; 1993:595-606.
32. Reisdorff EJ. Viral encephalitis. In: Reisdorff EJ, Roberts MR, Weigenstein JG, eds. Pediatric Emergency Medicine. Philadelphia: WB Saunders Co.; 1993:1056-1062.
33. Lipton JD, Schafermeyer RW. Central nervous system infectionsthe usual and the unusual. Pediatric emergencies. Emerg Med Clin North Am 1995;13:417-443.
34. Sundel R. Rheumatologic emergencies. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 3 rd ed. Baltimore: Williams and Wilkins; 1993:1074-1078.
35. Bell LM. Shock. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 3 rd ed. Baltimore: Williams and Wilkins; 1993:44-54.
36. Brown LW, Feigin RD. Bacterial meningitis: Fluid balance and therapy. Pediatr Ann 1994,23:93-98.
37. Blazer S, Berant M, Alon U. Bacterial meningitis: Effect of antibiotic treatment on cerebrospinal fluid. Ann J Clin Pathol 1983;80:386-387.
38. Kallio MJ, Kilpi T, Anttila M, et al. The effect of a previous visit to a physician on outcome after bacterial meningitis. JAMA 1994;10:787-791.
39. Radetsky M. Duration of symptoms and outcome in bacterial meningitis: An analysis of causation and the implications of a delay in diagnosis. Pediatr Inf Dis J 1992;9:694-701.
40. Talan DA, Gutermann JJ, Overturf GD, et al. Analysis of emergency department management of suspected bacterial meningitis. Ann Emerg Med 1989;18:856-862.
41. Meadow WL, Lantos J, Tanz RR, et al. Ought "standard care" be the "standard of care"? A study of the time to administration of antibiotics in children with meningitis. Am J Dis Child 1993;147:40-44.
42. Schaad UB, Kaplan SL, McCracken GH. Steroid therapy for bacterial meningitis. Clin Infect Dis 1995;20:685-690.
43. Kaplan SL. Dexamethasone for children with bacterial meningitisshould it be routine therapy ? Am J Dis Child 1989;143:290-291.
44. American Academy of Pediatrics, Committee on Infectious Diseases. Dexamethasone therapy for bacterial meningitis in infants and children. Pediatrics 1990;86:130-133.
45. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants with bacterial meningitis. N Eng J Med 1991;324:1525-1531.
46. Schaad UB, Lips U, Gnehm HE, et al. Dexamethasone therapy for bacterial meningits in children. Lancet 1993;342:457-461.
47. Jafari HS, McCracken GH. Dexamethasone therapy in bacterial meningitis. Pediatr Ann 1994;23:82-88.
48. Girgis NI, Farid Z, Kilpatrick ME, et al. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 1989;8:848-851.
49. Kanra GY, Ozen H, Secmeer G, et al. Beneficial effects of dexa-methasone in children with pneumococcal meningitis. Pediatr Infect Dis J 1995;14:490-494.
50. Chandy JC. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: Case report and review. Clin Infect Dis 1994;18:188-193.
51. Starke JR. Current chemotherapy for tuberculosis in children. Infect Dis Clin North Am 1992;6:215-238.
52. Committee on Infectious Diseases: American Academy of Pediatrics. Report 1994. Elk Grove Village, IL: American Academy of Pediatrics: 1994
53. Waler J, Rathore MH. Outpatient management of pediatric bacterial meningitis. Pediatr Infect Dis J 1995;14:89-92.
Physician CME Questions
26. The most common form of bacterial meningitis in the immunocompetent child greater than 3 months of age is:
A. Haemophilus influenzae.
B. Group B Streptococcus.
C. Neisseria meningitidis.
D. S. pneumoniae.
E. Listeria monocytogenes.
27. In children with indwelling CSF shunts, which of the following organisms is/are common causes of acute bacterial meningitis?
A. Haemophilus influenzae
B. Staphylococcus aureus
C. Neisseria meningitidis
D. S. pneumoniae
E. All of the above
28. Normal CSF findings in the neonate (up to 1 month of age) include:
A. protein of 100 mg/dL.
B. WBC count of 50 cells/hpf.
C. protein of 200 mg/dL.
D. none of the above; all are abnormal.
29. If a child of less than 1 year of age presents with fever and altered mental status, with no evidence of trauma after history and physical examination:
A. a CT scan should always be done prior to the LP.
B. an LP is indicated if there are no indications of bleeding diatheses, increased intracranial pressure (besides a bulging fontanelle), or a hemodynamic instability.
C. an LP should never be done in a child with a bulging fontanelle.
D. a CBC and toxicology screen should be done first.
30. Empiric antibiotic therapy for the child with acute bacterial meningitis and an indwelling CSF shunt (i.e., VP shunt) would be:
A. gentamicin and ampicillin.
B. ceftriaxone and ampicillin.
C. ceftriaxone or cefotaxime plus vancomycin.
D. ceftazidime.
31. Viral meningitis:
A. can be consistently differentiated from bacterial meningitis on the basis of typical CSF characteristics.
B. is common in late summer due to various enteroviruses.
C. can usually be clinically distinguished from bacterial meningitis.
D. always is benign with a good prognosis.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content