Despite advances in antimicrobial and general supportive therapies, central nervous system (CNS) infections remain a significant cause of morbidity and mortality in children. As classical signs and symptoms often are not present, especially in the younger children, diagnosing CNS infections is a challenge to the emergency department. Also, even for children who have had prompt diagnosis and treatment, a high frequency of neurologic sequelae remains. This often leads to legal action. The emergency clinician is faced with the daunting task of separating out those few children with CNS infections from the vast majority of children who come to the ED with less serious infections.
To develop bacterial meningitis, the invading organism must gain access to the subarachnoid space. This is usually via hematogenous spread from the upper respiratory tract where the initial colonization has occurred. Less frequently, there is direct spread from a contiguous focus (eg, sinusitis, mastoiditis, otitis media) or through an injury, such as a skull fracture.
The most common causative organisms in the first month of life are Escherichia coli and group B streptococci. Listeria monocytogenes infection also occurs in patients in this age range and accounts for 5-10% of cases. Neisseria meningitidis infections occurring in the first month of life have been reported. From 30-60 days, group B streptococcal infection occurs frequently, and the gram-negative enterics decline in frequency. Streptococcus pneumoniae, Haemophilus influenzae, and N meningitidis occur rarely in this age group. In those older than 2 months, S pneumoniae and N meningitidis currently cause the majority of the cases of bacterial meningitis. H influenzae may still occur, especially in children who have not received the Hib vaccine.
The most common causative organisms (eg, N meningitidis, S pneumoniae, H influenzae) contain a polysaccharide capsule that allows them to colonize the nasopharynx of healthy children without any systemic or local reaction. A concurrent viral infection may facilitate the penetration of the nasopharyngeal epithelium by the bacteria. Once in the bloodstream, the polysaccharide capsule allows the bacteria to resist opsonization by the classical complement pathway and, thus, inhibit phagocytosis.
Unusual bacteria occasionally cause meningitis. Pasteurella multocida is known to cause skin infections from cat or dog bites. A recent case described a 7-week-old infant with P multocida meningitis after exposure to dog saliva with no wound, emphasizing the need to protect young children from this pathogen. This infection, while rare, is associated with significant morbidity and mortality.
Salmonella meningitis should be suspected in any child with this organism grown at any other site in an unwell child or one younger than 6 months. Mothers known to be infected with Salmonella during pregnancy may put their child at risk. As therapy is different for Salmonella meningitis, while rare, it must be considered in the above situations.
The bacteremic phase allows penetration of the cerebrospinal fluid (CSF) through the choroid plexus. The CSF is poorly equipped to control infection because type-specific antibodies do not penetrate the blood brain barrier well and complement components are absent or in low concentrations.
The cell walls of both gram-positive and gram-negative bacteria contain potent triggers of the inflammatory response. In the gram-positive bacteria, teichoic acid is considered the major pathogenic component. In gram-negative bacteria, lipopolysaccharide or endotoxin is the major pathogenic component. These components are released in the CSF during bacterial growth and especially with the lysis of bacterial cells. Antibiotic therapy causes a significant release of the mediators of the inflammatory response.
The mediators of the inflammatory response include cytokines (tumor necrosis factor, interleukin 1, 6, 8, 10), platelet activating factor, nitric oxide, prostaglandins, and leukotrienes. These mediators cause disruption of the blood brain barrier, vasodilation, neuronal toxicity, meningeal inflammation, platelet aggregation, and activation of leukocytes. The capillary endothelial cell is the main site of injury in bacterial meningitis; thus, it is a vasculitis, which results in destruction of vascular integrity. The ultimate consequences are damage to the blood brain barrier, brain edema, impaired cerebral blood flow, and neuronal injury.
Because of the damage done by the body's response to the infection, various anti-inflammatory agents have been used in an attempt to decrease the morbidity and mortality of bacterial meningitis. Only dexamethasone occasionally has been proven effective.
Viral meningitis or aseptic meningitis is the most common infection of the CNS. It most frequently occurs in children younger than 1 year. Enterovirus is the most common causative agent and is a frequent cause of febrile illnesses in children. Other viral pathogens include paramyxoviruses, herpes, influenza, rubella, and adenovirus. Meningitis may occur in up to half of children younger than 3 months with enteroviral infection. Enteroviral infection can occur any time during the year but is associated with epidemics in the summer and fall. Viral infection causes an inflammatory response but to a lesser degree than bacterial infection. Damage from viral meningitis may be due to an associated encephalitis and increased intracranial pressure.
Fungal meningitis is rare but may occur in immunocompromised patients; children with cancer, previous neurosurgery, or cranial trauma; or premature infants with low birth rates. Most cases are in children who are receiving antibiotic therapy and, thus, usually are inpatients.
The etiology of aseptic meningitis caused by drugs is not well understood. This form of meningitis is infrequent in the pediatric population.
Encephalitis is a similar disease of the central nervous system. This disease is an inflammation of brain parenchyma. Often, a viral agent is responsible. Viral entry occurs through hematogenous or neuronal routes.
The more common form of encephalitis is transmitted by bites of mosquitoes and ticks, infected with the virus. The virus comes from the Togavirus, Flavivirus, and Bunyavirus families.
The more common types of encephalitis in the United States are La Crosse virus, eastern equine encephalitis virus, and St Louis virus. Often, these causes of encephalitis cause similar signs and symptoms. Confirmation and differentiation come from laboratory testing. However, its utility is limited to a number of identifiable pathogens.
West Nile virus is becoming a leading cause of encephalitis, caused by the arbovirus from the Flaviviridae family. Mosquitoes, spreading virus between its natural hosts, migrating birds, transmit it. Mosquitoes bite humans, who become infected with the virus. However, human hosts are dead-end hosts for the virus.
Most humans do not develop the disease. Approximately 1 symptomatic infection develops for every 120-160 asymptomatic ones. The young and old are at risk of developing symptomatic disease.
It has become a greater public health issue, given that spread occurs with migratory birds. The first cases were identified in New York City in 1999, with additional cases being identified in the following years across the United States.
Encephalitis can be transmitted by other means. Herpetic encephalitis and rabies are two examples, where transmission occurs by direct contact and mammalian bites, respectively. In the case of herpetic encephalitis, there is evidence of virus reactivation and subsequent intraneuronal transmission, leading to encephalitis.
The advent of vaccine has changed the incidence of disease. The incidence of disease caused by H influenzae, S pneumoniae, and N meningitidis has decreased.
The advent of universal Hib vaccination in developed countries has lead to the reduction of more than 99% of invasive disease. The vaccine is directed against the H influenzae type b strain. This protection continues even when Hib is coadministered with other vaccines. Just as important, the vaccine continues to confer immunity into later childhood.
A similar effect occurs with the advent of pneumonococcal vaccine. This is true for the pneumococcal polysaccharide vaccines conjugated to various proteins. Given at ages 2, 4, and 6 months, this vaccine has reduced invasive disease more than 90%. Age groups most affected are those younger than age 2 years and those aged 2-5 years. This was proven in a surveillance study in Louisville, Kentucky.[1] Nearly half of those with pneumococcal disease are caused by nonvaccine serotypes.[2, 3]
However, vaccine for Neisseria has not been efficacious in younger children. This is due to poor immunogenic response. Current recommendation targets immunization for children older than age 2 years and high-risk patients with asplenic and terminal complement deficiencies. In addition, young adults living in close quarters, such as dormitories or military barracks, will benefit.
The incidence of neonatal meningitis has shown no significant change in the last 25 years. Viral meningitis is the most common form of aseptic meningitis and, since the introduction of mumps vaccine, is caused by enteroviruses in up to 85% of cases. Incidence of encephalitis is more difficult to estimate because of difficulty in establishing the diagnosis. One report estimates an incidence of 1 in 500-1000 in the first 6 months of life.
International
In a survey by the Hib and Pneumococcal Working Group, the incidence of meningitis in 2000 varied from regions across the world. The overall incidence of pneumococcal meningitis was 17 cases per 100,000, with the highest incidence in Africa at 38 cases per 100,000 and the lowest incidence in Europe at 6 cases per 100,000. The overall death rate was 10 cases per 100,000. The highest death rate was 28 cases per 100,000 in Africa, and the lowest death rates were 3 cases per 100,000 in Europe and Western Pacific regions.[4]
A similar trend was identified for Hib meningitis. The overall incidence of Hib meningitis in 2000 was 31 cases per 100,000. The African region had the highest rate at 46 cases per 100,000, and Europe had the lowest rate at 13 cases per 100,000. The death rate was 13 cases per 100,000. The highest death rate was 31 cases per 100,000 in Africa, and the lowest death rate was 4 cases per 100,000 in Europe.[5]
Mortality/Morbidity
Morbidity and mortality rates depend on the infectious agent, age of the child, general health, and prompt diagnosis and treatment. Despite improvement in antibiotic and supportive therapy, a significant mortality and morbidity rate remains.
The overall mortality for bacterial meningitis is 5-10% and varies with causative organism and age. Neonatal meningitis has a mortality rate of 15-20%. In older children, the mortality rate is 3-10%. Meningitis from S pneumoniae has the highest mortality rate (26.3-30%); H influenzae type B has a 7.7-10.3% mortality rate; N meningitidis has the lowest mortality rate of the most common organisms, at 3.5-10.3%.
Up to 30% of children have neurological sequelae. This varies by organism, with S pneumoniae having the highest rate of complications.
One study indicates that the complication rate from S pneumoniae meningitis did not vary if the infection was from a penicillin sensitive or resistant strain. This study showed that dexamethasone did not improve outcomes.[6]
Some studies have shown the incidence of profound bilateral hearing loss, up to 4% in all bacterial meningitis cases.[7] Sensorineural hearing loss is one of the most frequent problems. Children at greatest risk for hearing loss include those with evidence of increased intracranial pressure, abnormal findings on CT scan, male sex, low glucose levels in CSF, infection by S pneumoniae, and nuchal rigidity.
As many of the children affected are very young and cognitive and motor skills are immature, some of the sequelae may not be recognized for years. A recent study followed children who recovered from meningitis for 5-10 years. They found 1 in 4 school-aged meningitis survivors had either serious and disabling sequelae or a functionally important behavior disorder or neuropsychiatric or auditory dysfunction that impaired their performance in school.
Viral meningoencephalitis: Enteroviral infection usually has few complications. Herpes simplex and arbovirus infections, in addition to viral infections in AIDS patients, can result in severe neurological disease.
Tuberculous meningitis: Morbidity and mortality rates are related to the stage of the disease. Stage I has a 30% significant morbidity, stage II 56%, and stage III 94%.
Race
Bacterial meningitis more frequently occurs in black and Hispanic children. This is thought to be related to socioeconomic rather than racial factors.
Sex
Prevalence of bacterial meningitis is higher in males. A recent report from Finland showed males more often had mumps and varicella encephalitis, whereas females had adenoviral and Mycoplasma encephalitis more often.
Age
For both meningitis and encephalitis, the greatest occurrence is in children younger than 4 years with a peak incidence in those aged 3-8 months.
The younger the child, the less likely he or she is to exhibit the classic symptoms of fever, headache, and meningeal signs.
Meningitis in the neonatal period is associated with maternal infection or pyrexia at delivery. The child younger than 3 months may have very nonspecific symptoms, including hyperthermia or hypothermia, change in sleeping or eating habits, irritability or lethargy, vomiting, high-pitched cry, or seizures.
Meningismus and a bulging fontanel may be observed but are not needed for diagnosis.
A child who is quiet at rest but who cries when moved or comforted may have meningeal irritation (paradoxical irritability).
After age 3 months, the child may display symptoms more often associated with bacterial meningitis, with fever, vomiting, irritability, lethargy, or any change in behavior.
After age 2-3 years, children may complain of headache, stiff neck, and photophobia.
The clinical course may be brief and fulminant with rapid progression of symptoms or may follow a more gradual course with several days of upper respiratory infection progressing to more severe symptoms. The fulminant course is more often associated with N meningitidis infection.
Viral meningitis
In areas with widespread vaccination of children, enteroviruses are the most common causes of viral meningitis. The onset is variable and may have several days of fever, anorexia, and general malaise. It also may present as a rather abrupt onset of fever, nausea, vomiting, and headache.
Additional symptoms are shared with enteroviral infections, such as pharyngitis, conjunctivitis, and myositis.
Other causes of viral meningitis also may be associated with encephalitis. Arboviral infections frequently have associated encephalitis and seizures.
Adenoviral, mumps, and varicella-zoster infections tend to be more severe than enteroviral infections, and often evidence of encephalitis is present.
In areas with low vaccination rates, mumps virus is often the most frequent cause of meningitis.
Fungal meningitis occurs in immunocompromised patients and has a variable presentation.
Aseptic meningitis may be caused by drugs, usually nonsteroidal anti-inflammatory drugs (NSAIDs), IVIG, and antibiotics. A recent report was of a pediatric patient with a trimethoprim-sulfamethoxazole–induced meningitis. Symptoms were similar to those of viral meningitis. Symptoms may occur within minutes of ingestion of the drug.
Encephalitis
Diagnosis for the causative viral agent is aided by historical facts. Information such as season of year, travel, activities, and exposure to animals helps with diagnosis.
A distinction between viral encephalitis and postinfectious encephalomyelitis is important because management and prognosis are different. With postinfectious encephalomyelitis, the usual presentation is a nonspecific respiratory viral syndrome.
Physical examination findings are widely variable based on age and infecting organism. It is important to remember that the younger the child, the less specific the symptoms.
In the young infant findings that definitely point to meningitis are rare.
The infant may be febrile or hypothermic.
Bulging of the fontanel, diastasis of the sutures, and nuchal rigidity point to meningitis but are usually late findings.
As the child grows older, the physical examination becomes more reliable.
Meningeal signs (eg, headache, nuchal rigidity, positive Kernig and Brudzinski signs) should be sought, and their presence or absence recorded.
A definitive diagnosis of meningitis requires examination of CSF via lumbar puncture. Presence or absence of classic meningeal signs and symptoms should not be used as the sole criteria for referring patients for further diagnostic testing.[8]
Focal neurological signs may be present in up to 15% of patients and are associated with a worse prognosis.
Seizures occur in up to 30% of children with bacterial meningitis.
Obtundation and coma occur in 15-20% of patients and are more frequent with pneumococcal meningitis.
Encephalitis may present like meningitis or the symptoms of the systemic viral infection may predominate.
Encephalitis
Physical findings for encephalitis are fever, headache, and decreased neurological function. Decreased neurological functions include altered mental status, focal neurological function, and seizure activities. These findings can help identify the virus type and prognosis.
In West Nile virus, the signs and symptoms are nonspecific and include fever, malaise, periocular pain, lymphadenopathy, and myalgia.
West Nile virus has some unique physical findings including fine, maculopapular, erythematous rash; proximal muscle weakness; and flaccid paralysis. This rash is commonly found in children.
Critically ill patients have neurological dysfunction, such as altered mental status and cranial nerve dysfunction, as the major physical finding.
Bacterial antigen studies can be performed on urine and serum; they can be useful in cases of pretreated meningitis. However, a negative bacterial antigen study result does not rule out meningitis.
Imaging studies rarely are required in the initial management of meningitis or encephalitis when the clinical presentation is typical. Exceptions include the need to rule out other pathology before performing an LP or when focal neurologic signs are present.
Imaging may be useful to check for abscesses, subdural effusions, empyema, or hydrocephalus.
Normal CT scan findings do not rule out increased intracranial pressure (ICP).
Preliminary studies have suggested procalcitonin to be a useful biomarker to the presence of bacterial meningitis. One study suggests that its use will enhance a sensitivity of a clinical decision rule, Bacterial Meningitis Score by Nigrovic et al.[9, 10, 11]
The most important laboratory study is examination of CSF. The lumbar puncture (LP) should include opening and closing pressure in the cooperative patient.
Cell count
Gram stain
Culture and sensitivity
Glucose
Protein and antigen
Acid-fast bacillus
Fungal stains
Bacterial meningitis
White blood cell (WBC) counts over 1000/mm3 usually are caused by bacterial infections. Counts of 500-1000/mm3 may be bacterial or viral and need further evaluation. Lower counts are usually associated with viral infections. The total WBC count cannot definitely distinguish between bacterial and other causes. It was generally believed that a predominance of polymorphonucleocytes (PMNs) pointed to bacterial meningitis, but this has been unreliable. To differentiate bacterial and aseptic meningitis on the basis of percentage and absolute number of premature neutrophils (ie, bands) has been nondiagnostic.[12]
Gram stain may aid in diagnosis, but the diagnosis may be missed in up to 30-40% of cases of culture-proven disease. The sensitivity of a positive Gram stain is 67%.[13]
The protein concentration usually is elevated in bacterial meningitis, but it also is elevated by a traumatic tap. The glucose is usually reduced in bacterial meningitis. Normal CSF glucose should be greater than two-thirds that of the serum glucose. Levels less than 50% of serum are suggestive of bacterial meningitis.
Ancillary tests, such as total protein concentration, glucose concentration, and percent of neutrophils in CSF, are not helpful to for diagnosis, when the cell counts are low (less than 30/mm3). Its utility is useful only when they are highly abnormal.
Latex agglutination tests are available to test for S pneumoniae, H influenzae, group B Streptococcus, and N meningitidis. A negative result, however, does not rule out bacterial infection.
Even with normal CSF results, the fluid should be sent for culture. N meningitidis and S pneumoniae are known to give normal CSF results.
In an evidence-based article, Ray et al found that meningitis may still exist in 10% of children who have normal CSF analysis.[14] Their recommendation is to treat any child with antibiotics if there is a risk of bacterial meningitis.
In cases where antibiotic administration leads to CSF sterilization, polymerase chain reaction (PCR) may have a role in identifying the pathogen. PCR is able to identify the pathogen quickly and accurately. The sample does not need to have a high number of organisms. However, this test needs further validation.
Nigrovic et al found that Gram stain results (white blood cell count and the absolute neutrophil count) in the CSF were not affected by pretreatment with antibiotics (p = 0.86). However, the rates of positive cerebrospinal fluid culture (p = 0.001) and blood culture (p = 0.05) were lower with pretreatment with antibiotics. After pretreatment with antibiotics for ≥12 hours, these patients have higher CSF glucose levels (p = 0.005) and lower CSF protein levels (p = 0.008).[15]
Procalcitonin has shown promise as a biomarker to distinguish bacterial meningitis from aseptic meningitis. From their retrospective analysis of admitted patients with meningitis, Dubos et al found a 99% sensitivity and 83% specificity for procalcitonin at 0.5 ng/mL.[16]
Clinical decision rule
There is an interest to differentiate bacterial meningitis and aseptic meningitis. To date, 5 clinical decision rules exist. These clinical decision rules identify low-risk patients by scoring or modeling clinical variables, blood variable, and CSF variables. With any clinical decision rule, they are used to identify patients at risk of meningitis. Those who are at low risk can avoid parenteral antibiotic and hospitalization.
The clinical decision rule by Nigrovic et al[11] has shown high accuracy and simplicity of use. Comparison among the 5 clinical decision rules has not been performed. In addition, general applicability of these rules has not been validated.
Viral meningitis
The WBC count in viral meningitis is usually below 500/mm3, with greater than 50% lymphocytes.
The protein may be elevated.
The glucose level may be normal or low.
Gram stain results are negative.
Encephalitis
In addition to the studies for meningitis, an EEG, CT scan, and MRI have been used for evaluation.
More recently, PCR has been used for diagnosis.
CSF analysis shows pleocytosis (predominantly mononuclear cells) and high levels of protein. A small percentage (3-5%) of samples have normal CSF. Identification of viral antigen or nucleic acid may provide some diagnostic help.
Serial antibody analysis is helpful for prognostic purposes. Routine measurements do not aid in the treatment during the acute phase. New ELISA and PCR assays are available for diagnosis.
In cases of West Nile virus, CSF shows pleocytosis and moderately elevated protein levels. CT shows no abnormalities. MRI may show enhancement of meninges and periventricular regions. Diagnosis test is WNV ELISA. However, this test has cross reactivities to other flaviviruses.
Traumatic LP
If bleeding occurs during the procedure and the CSF is contaminated with blood, the interpretation becomes more difficult.
The use of corrected WBC:RBC ratio (1:500) and percent of neutrophils to "normalize" the cell count was shown to have limited utility in predicting those with meningitis. The "corrected CSF" was shown to underestimate the true white blood cell count, causing clinicians to underdiagnosis borderline meningitis cases.
Formulas to adjust for white blood cell count in the CSF analysis have not increased the specificity or sensitivity in traumatic lumbar puncture. These LPs were performed in neonates.[17]
In any situation when a traumatic LP occurs and the interpretation is difficult, it is better to treat and wait for the results of the CSF culture.
In very bloody LPs, a drop of the fluid on the sterile dressing usually will produce a double ring if there is CSF fluid present.
Prehospital care usually is confined to transporting children who are critically ill or have experienced a seizure from the meningitis or encephalitis.
General supportive care is required depending on the child's condition.
Subsequent diagnosis of a potentially transmissible disease must be communicated to prehospital care providers, especially with N meningitidis infections.
Immediate stabilization and support of the critically ill or seizing child is necessary.
When meningitis or encephalitis is suspected, a lumbar puncture (LP) is indicated. Adequate analgesia is essential, with recent studies indicating only 1 in 7 infants receive any pain management during LP.[18]
If the child's condition is unstable or there is suspicion of increased intracranial pressure, the LP should be delayed.
It is very important that antibiotic therapy is immediately commenced in the ill child and not delayed until after the LP.
If prompt LP cannot be performed, administration of antibiotics should be initiated. However, sterilization of CSF will occur. It was previously thought that sterilization occurs within 2-3 hours. However, in a retrospective study, complete sterilization was found to occur within 2 hours for meningococcal meningitis. With pneumonococcal infections, sterilization occurred within 4 hours.
If the child is hemodynamically stable, intravenous fluids should be administered at maintenance. Careful record of the patient's weight, urine specific gravity, and serum osmolarity will help guide further fluid therapy. Patients who present with dehydration need rehydration and should not have fluid restriction. Seizures should be treated promptly and should be expected at any time during the initial management.
Clinical Context:
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin binding proteins.
Clinical Context:
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin binding proteins.
Clinical Context:
Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous. Adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.
Clinical Context:
Not used frequently since introduction of third-generation cephalosporins. Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Clinical Context:
Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.
IV antibiotics are required for bacterial meningitis. If the causative organism is unknown, antibiotics regimens can be based on the child's age.
Infants younger than 30 days, ampicillin and an aminoglycoside or a cephalosporin (cefotaxime) are recommended.
Children 30-60 days old, ampicillin and a cephalosporin (ceftriaxone or cefotaxime) can be used. Since S pneumoniae occasionally occurs in this age range, vancomycin should be considered instead of ampicillin.
In older children, a cephalosporin (eg, cefotaxime, ceftriaxone) or ampicillin plus chloramphenicol can be used.
Incidence of resistant S pneumoniae is increasing. If this is considered to be a potential pathogen, add vancomycin to the therapeutic regimen. Use of penicillin or ampicillin in the 3 months prior to illness is associated with increased risk of infection with resistant S pneumoniae.
Uncertainty exists as to the benefits of corticosteroids as adjuvant therapy for meningitis. In adults, corticosteroids, given prior to or along with the first dose of antibiotics, reduce morbidity and mortality by hearing loss, long-term neurological sequelae, and deaths. These findings were applicable to high-income countries.
From their recent meta-analysis, Mongelluzzo et al found no benefits of corticosteroids in children. The survival and time to hospital discharge were comparable between the corticosteroid treatment group and the nontreatment group. Even when comparing age and causative organism, these two groups did not differ in survival and hospital discharge. To date, the role of corticosteroids as an adjuvant therapy is of uncertain benefits.[19]
Clinical Context:
Inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Take on an empty stomach.
Clinical Context:
Prodrug activated by phosphorylation by virus-specific thymidine kinase that inhibits viral replication. Herpes virus thymidine kinase (TK), but not host cells TK, uses acyclovir as a purine nucleoside, converting it into acyclovir monophosphate, a nucleotide analogue. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication.
Has affinity for viral thymidine kinase and once phosphorylated causes DNA chain termination when acted on by DNA polymerase. Inhibits activity of both HSV-1 and HSV-2.
Children with suspected bacterial meningitis should be admitted to the hospital for intravenous antibiotic therapy.
Adequate fluid administration is necessary to maintain perfusion, especially cerebral perfusion. Fluid restrictions (to prevent cerebral edema) may be more harmful because patients may be under resuscitated.
Children with suspected viral meningitis who appear well may receive care as outpatients, provided follow-up care can be ensured.
With continued pressure to decrease hospital stays, there are occasions when patients may be discharged from the hospital to continue parenteral antibiotics at home.
Routine childhood immunizations have been shown to effectively decrease the incidence of certain types of meningitis and encephalitis. Routine vaccination with Haemophilus influenzae type b vaccine (ActHIB, Hiberix, Liquid PedvaxHIB) has greatly diminished the incidence of meningitis.[69] The meningococcal A C Y and W-135 vaccine (Menactra) is also used in children as young as 9 months old who are at high risk and as a routine vaccine in early adolescents. A Hib conjugate and meningococcal serogroups C&Y conjugate combination vaccine, MenHibrix, was approved by the FDA in June 2012 for use in infants. The combination vaccine is indicated in children aged 6 weeks to 18 months for active immunity against invasive disease. It is given as a 4-dose series usually at well-baby checkups.
Antibiotic prophylaxis is recommended for all household contacts in those households with at least 1 unvaccinated child younger than 48 months in patients with H influenzae meningitis. Prophylaxis should be started as soon as possible in all contacts in the household if any child is younger than 12 months. Careful observation of any contacts and immediate evaluation is warranted if a fever develops.
Prophylaxis is recommended for all persons in contact with oral secretions of patients with N meningitidis meningitis. This includes a health care worker who performed mouth-to-mouth resuscitation, intubation, or suctioning.
The use of rifampin, ceftriaxone, and ciprofloxacin has been effective prophylaxis. In a systematic review, ciprofloxacin and ceftriaxone are more effective up to 4 weeks of posttreatment against resistant strains of N meningitidis.
Despite early aggressive management, the complications from bacterial meningitis remain significant.
In the neonatal period, the mortality rate is 15-25%.
After the neonatal period, the mortality rate drops to about 5% with appropriate care.
The morbidity rate is up to 40% depending on the causative organism and delay in therapy.
Hib meningitis has up to 15% rate of permanent neurological sequelae.
Focal neurological sequelae may occur in 10-15% of patients. These problems are hemiparesis, facial palsy, visual field defects, hearing loss, and cranial nerve palsies.
Seizures may occur at any point of the patient's course. Seizures that continue after the fourth day of hospitalization are focal in nature or are difficult to control have a greater likelihood of neurological sequelae.
Most children with enteroviral meningitis have an uncomplicated course.
Jeffrey Hom, MD, MPH, FACEP, FAAP, Assistant Professor, Department of Pediatrics/Emergency Services and Department of Emergency Medicine, New York University School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Robert Allan Felter, MD, FAAP, CPE, FACPE, Professor of Clinical Pediatrics, Department of Pediatrics, Georgetown University School of Medicine; Medical Director, Pediatric Emergency Medicine and Inpatient Services, Inova Loudoun Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Garry Wilkes, MBBS, FACEM, Director of Emergency Medicine, Calvary Hospital, Canberra, ACT; Adjunct Associate Professor, Edith Cowan University, Western Australia
Disclosure: Nothing to disclose.
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center
Disclosure: Nothing to disclose.
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Richard G Bachur, MD, Associate Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston
