Pediatric Bacterial Meningitis Clinical Presentation

Symptoms of neonatal bacterial meningitis are nonspecific and include the following:

• Poor feeding
• Lethargy
• Irritability
• Apnea
• Listlessness
• Apathy
• Fever
• Hypothermia
• Seizures
• Jaundice
• Bulging fontanelle
• Pallor
• Shock
• Hypotonia
• Shrill cry
• Hypoglycemia
• Intractable metabolic acidosis

The following symptoms are readily recognized as associated with meningitis in infants and children:

• Nuchal rigidity
• Opisthotonos
• Bulging fontanelle
• Convulsions
• Photophobia
• Headache
• Alterations of the sensorium
• Irritability
• Lethargy
• Anorexia
• Nausea
• Vomiting
• Coma
• Fever (generally present, although some severely ill children present with hypothermia)

The following may be noted on the physical examination in patients with bacterial meningitis:

• Neonatal

  • A high index of suspicion and awareness of risk factors usually results in early diagnosis and prompt treatment.
  • Cardinal signs of meningitis (eg, fever, vomiting, stiff neck) are rarely present. For neonatal meningitis, these signs are the exception, rather than the rule.
• Infants and children

  • Kernig and Brudzinski signs are helpful indicators when present, but they may be absent (along with nuchal rigidity) in the very young, debilitated, or malnourished infants.
  • Skin findings range from a nonspecific blanching, erythematous, maculopapular rash to a petechial or purpuric rash, most characteristic of meningococcal meningitis.
  • Patients may also have other foci of infection. Presenting symptoms may point toward those foci, causing unnecessary delay in diagnosis of bacterial meningitis.
  • Approximately 15% of patients have focal neurologic signs upon diagnosis. The presence of focal neurologic signs predicts a complicated hospital course and significant long-term sequelae.
  • Generalized or focal seizures are observed in as many as 33% of patients. Seizures that occur during the first 3 days of illness usually have little prognostic significance. However, prolonged or difficult-to-control seizures, especially when observed beyond the fourth hospital day, are predictors of a complicated hospital course with serious sequelae.
  • In later stages of the disease, a few patients develop focal CNS symptoms and other systemic signs (eg, fever) indicating a significant collection of fluid in the subdural space. Incidence of subdural effusion is independent of the bacterial organism causing meningitis.
  • Approximately 6% of affected infants and children show signs of disseminated intravascular coagulopathy and endotoxic shock. These signs are indicative of a poor prognosis.

The causes are as follows:

• Etiology of neonatal meningitis

  • Bacteria are often acquired from the maternal vaginal flora. Gram-negative enteric flora and group B streptococci are predominant pathogens. In premature newborns who receive multiple antibiotics, hyperalimentation, and who undergo various surgical procedures, Staphylococcus epidermidis and Candida species are uncommon etiologies but are reported in greater frequency in neonates. L monocytogenes is another well known but fairly uncommon etiologic pathogen.
  • Early onset group B streptococcal meningitis occurs during the first 7 days of life, a consequence of maternal colonization and the absence of protective antibody in the neonate; it is often associated with obstetric complications. The disease is seen most often in premature or low birth weight babies. Pathogens are acquired before or during the birth process.
  • Late-onset meningitis is defined as disease occurring after 7 days of life. Etiologic agents include perinatally acquired and nosocomial pathogens. S agalactiae (group B streptococci) are classified into 5 distinct serotypes: Ia, Ib, Ic, II, and III. Although these serotypes occur with almost equal frequency in the early onset of disease, serotype III causes 90% of late-onset disease.
  • Use of respiratory equipment in the nursery increases the risk of infection caused by Serratia marcescens,Pseudomonas aeruginosa, and Proteus species. Invasive devices predispose infants to the infections caused by Staphylococcus epidermidis and Pseudomonas, Citrobacter, and Bacteroides species.
  • Infection with Citrobacter diversus, Citrobacter koseri, Salmonella species, and Proteus species though uncommon, carries a high mortality rate. These patients often develop brain abscesses, particularly Citrobacter where meningitis produces brain abscesses in 80-90% of cases.
• Etiology of meningitis in infants and children: In children older than 4 weeks, S pneumoniae and N meningitidis are the most common etiologic agents. H influenzae type b has essentially disappeared in countries where the conjugate vaccine is routinely used.
• S pneumoniae meningitis

  • S pneumoniae are lancet-shaped, gram-positive diplococci and are the leading cause of meningitis. Of the 84 serotypes, numbers 1, 3, 6, 7, 14, 19, and 23 are the ones most often associated with bacteremia and meningitis.
  • Children of any age may be affected, but incidence and severity are highest in very young and elderly persons.
  • In patients with recurrent meningitis, predisposing factors are anatomic defects, asplenia, and primary immune deficiency. Often history includes recent or remote head trauma.
  • This organism also has a predilection for causing meningitis in patients with sickle cell disease, other hemoglobinopathies, and functional asplenia. Immunity is type specific and long lasting.
  • S pneumoniae colonizes the upper respiratory tract of healthy individuals; however, disease often is caused by a recently acquired isolate. Transmission is person-to-person, usually by direct contact, and secondary cases are rare. The incubation period varies from 1-7 days, and infections are more prevalent during the winter when viral respiratory disease is prevalent. The disease often results in sensorineural hearing loss, hydrocephalus, and other CNS sequelae. Prolonged fever despite adequate therapy is common in patients with meningitis caused by this organism.
  • Effective antimicrobial therapy can eradicate the organism from nasopharyngeal secretions within 24 hours. Over the past decade, pneumococci have developed resistance to a variety of antibiotics. Although this development is seen worldwide, resistance rates to penicillin vary from 10-60%. Recent multicenter surveillance results of pneumococci isolated from the cerebrospinal fluid (CSF) show resistance rates of 20% and 7% to penicillin and ceftriaxone, respectively. Penicillin resistance in pneumococci is due to alterations in enzymes necessary for growth and repair of the penicillin-binding proteins; thus, beta-lactamase inhibitors offer no advantage. Penicillin-resistant pneumococci often demonstrate resistance to sulfamethoxazole/trimethoprim, tetracyclines, chloramphenicol, and macrolides. However, selected third-generation cephalosporins (eg, cefotaxime, ceftriaxone) do exhibit activity against most penicillin-resistant isolates.
  • To date, all isolates remain susceptible to vancomycin and various oxazolidinones. Several of the new fluoroquinolones (eg, levofloxacin), although contraindicated in children, have excellent activity against most pneumococci and achieve adequate CNS penetration.
  • Tolerance, a trait distinct from resistance, was first described in 1970 to characterize bacteria that stop growing in the presence of antibiotic, yet do not lyse and die. Pneumococci tolerant to penicillin and vancomycin have been previously described in literature and a subsequent link to recrudescence in meningitis described in one child. The overall incidence and clinical impact of such bacterial strains is unknown. However, this characteristic should be kept in mind in cases of recurrent pneumococcal meningitis.
• N meningitidis meningitis

  • N meningitidis are gram-negative, kidney bean–shaped organisms and frequently are found intracellularly. Organisms are grouped serologically on the basis of capsular polysaccharide; A, B, C, D, X, Y, Z, 29E, and W-135 are the pathogenic serotypes. In developed countries, serotypes B, C, Y, and W-135 account for most childhood cases. Group A strains are most prevalent in developing countries and have resulted in epidemics of meningococcal meningitis throughout the world and in outbreaks in military barracks. The upper respiratory tract frequently is colonized with meningococci, and transmission is person-to-person by direct contact through infected droplets of respiratory secretions, often from asymptomatic carriers. The incubation period is generally less than 4 days, with a range of 1-7 days.
  • Most cases occur in infants aged 6-12 months; a second lower peak occurs among adolescents. A petechial or purpuric rash frequently is seen. Mortality rates are significant in patients who have a rapidly progressive fulminant form of the disease. Normocellular CSF also has been reported in patients with meningococcal meningitis. Most deaths occur within 24 hours of hospital admission in patients who have features associated with poor prognosis (eg, hypotension, shock, neutropenia, extremes of ages, petechiae and purpura of < 12 h duration, disseminated intravascular coagulopathy, acidosis, presence of organism in WBC on peripheral smear, low erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP], serogroup C disease).
  • Higher rates of fatality and physical sequelae such as scarring and amputation are reported in survivors of serogroup C disease. Long-term sequelae are rare in patients who have an uneventful hospital course.
• H influenzae type b meningitis

  • H influenzae type b is a pleomorphic gram-negative rod whose shape varies from a coccobacillary form to a long curved rod. H influenzae meningitis occurs primarily in children who have not been immunized with H influenzae type b vaccine, with 80-90% of the cases occurring in children aged 1 month to 3 years. By age 3 years, a significant number of nonimmunized children acquire antibodies against the capsular polyribophosphate of H influenzae type b, which are protective.
  • Mode of transmission is person-to-person by direct contact through infected droplets of respiratory secretions. The incubation period generally is less than 10 days.
  • Current mortality rates are less than 5%. Most fatalities occur during the first few days of the illness.
  • Plasmid-mediated resistance to ampicillin due to the production of beta-lactamase enzymes by bacterium is being reported increasingly, and now 30-35% of the isolates are ampicillin resistant. As many as 30% of cases may have subtle long-term sequelae. Administration of dexamethasone early in treatment reduces the morbidity and sequelae.
• L monocytogenes meningitis: L monocytogenes causes meningitis in newborns, immunocompromised children, and pregnant women. The disease also has been associated with the consumption of contaminated foods (eg, milk, cheese). Most cases are caused by serotypes Ia, Ib, and IVb. Signs and symptoms in patients with listerial meningitis tend to be subtle, and diagnosis often is delayed. In the laboratory, this pathogen can be misidentified as a diphtheroid or as hemolytic streptococci.
• Other causes

  • S epidermidis and other coagulase-negative staphylococci frequently cause meningitis and CSF shunt infection in patients with hydrocephalus or following neurosurgical procedures.
  • Immunocompromised children can develop meningitis caused by species of Pseudomonas, Serratia,Proteus, and diphtheroids.