While the diagnosis is simple when patients come with classic symptoms of photophobia, nuchal rigidity, severe headache, or mental status changes, this is not generally the case at the initial evaluation. There is a continuum from a complete absence of clinical signs or symptoms at the time the first bacteria cross the blood–brain barrier to severe symptoms.
The point in that continuum of symptoms when the child is seen and the rate at which the disease is progressing will determine how difficult it will be for the clinician to recognize the child as having meningitis. It is for this reason that approximately half of all patients ultimately diagnosed with bacterial meningitis will visit a clinician during the course of their illness and be sent home from the encounter without meningitis being considered.4
The highest risk for meningitis during childhood is in the first month or two of life and at this age the clinical signs are few. Therefore, a lumbar puncture is generally warranted in the evaluation of the febrile infant younger than 2 months. After 2 months of age the diagnosis remains a challenge but more clinical cues are available to the clinician experienced in evaluating young children.
Children with prior antibiotic therapy during the illness can be more difficult to diagnose. Pretreated patients are less likely to have fever at examination, less likely to have altered mental status, and will have longer duration of symptoms at diagnosis.5Table 16–2 summarizes the pertinent history and physical examination in the evaluation of patients suspected of having meningitis. Figure 16–2 is a flow diagram for the diagnostic approach for patients being evaluated for meningitis.
Cerebrospinal Fluid Studies
The CSF should be sent for cell count, glucose, protein, Gram stain, and bacterial culture. A CSF fungal culture should also be performed in premature infants and in children with other immunocompromising conditions. Most patients with bacterial meningitis will have an elevated CSF white blood count (WBC) count with 80% or more polymorphonuclear cells, the CSF glucose will be low in about 50% and the CSF protein concentration is generally elevated. The CSF culture is positive in about 80% of patients and the culture is positive within 24–48 hours unless antimicrobials were given prior to lumbar puncture.
For the infant under 1 month of age with CSF pleocytosis, no prediction rule can reliably exclude bacterial meningitis and these infants should be treated as possibly having bacterial meningitis until the results of CSF culture are known. Further, not even normal CSF parameters exclude bacterial meningitis as 10% of neonates with bacterial meningitis will not have a CSF pleocytosis6–8 and a majority of very low birth weight (≤1.5 kg) neonates with bacterial meningitis have no CSF pleocytosis at diagnosis (by positive CSF culture).6
For older infants and children with CSF pleocytosis, a multicenter review of pediatric cases of bacterial meningitis clearly demonstrated that children older than 1 month with CSF pleocytosis (and no antibiotic pretreatment) can be considered at very low risk of bacterial meningitis if the Gram stain has no organisms, the CSF absolute neutrophil count is ≤1000 cells/mm3, the CSF protein is ≤80 mg/dL, the peripheral blood absolute neutrophil count is ≤10,000 cells/mm3, and there is no history of seizure before or at the time of presentation.7 Nonetheless, even with these serially applied low-risk criteria, 2 of 121 children with bacterial meningitis had none of these risk factors for a sensitivity of 98% (95% confidence intervals: 94–100%). Both of these children were younger than 2 months of age.
Among patients beyond the first months of life, the serum procalcitonin (≥0.5 ng/mL), C-reactive protein (≥20 mg/L), CSF lactate, and the CSF glucose or CSF glucose to serum glucose ratio can all be helpful in distinguishing bacterial from nonbacterial causes of acute meningitis.8–11 While not routinely available the CSF levels of interleukin 6 (IL-6) and tumor necrosis factor are also much higher in patients with bacterial versus aseptic meningitis.12
Patients with bacterial meningitis have a predominance of polymorphonuclear cells before treatment. Approximately half of patients with aseptic or demonstrated enteroviral meningitis will also have a CSF polymorphonuclear cell predominance. Symptom duration does reliably result in a change in the CSF white blood profile, so serial lumbar punctures for this purpose are not recommended.13,14
Latex agglutination studies of the CSF for bacterial antigens do not typically provide any benefit and are not routinely recommended.15 Polymerase chain reaction (PCR) tests for bacteria are not readily available and have not shown much benefit beyond culture but some available viral PCR tests are faster and more sensitive than viral culture and should be considered for specific etiologies. Because enteroviruses are common causes of meningitis and enterovirus PCR tests are now readily available, it is suggested that if the turn around time for this test at your institution is usually ≤48 hours this test should be routinely considered. Previous studies have demonstrated a decrease in hospital length of stay when enterovirus PCR testing is routinely performed during enteroviral season.16,17 Because it is slower than most routine bacterial culture or PCR tests, the routine use of viral culture is not recommended. Where herpes simplex meningoencephalitis is a possible concern a herpes simplex PCR should be sent.
A positive Gram stain or growth of a pathogen in CSF culture definitively identifies bacterial meningitis. Unfortunately the diagnosis is more difficult to establish or exclude in the patient who has received antibiotic treatment prior to obtaining CSF for examination and culture. Pretreated patients are less likely to have a positive CSF Gram stain or culture.5
While bacteria can be recovered in some circumstances for one or more days after initiation of antimicrobial therapy, the CSF is sterilized in 2 hours or less with meningococcal infections, in 4 to 12 hours with pneumococcal infections, and as early as 8 hours with group B streptococcal infections.18Table 16–3 includes suggested studies to be ordered in the evaluation of the patient with suspected meningitis.
Table 16–3. Key Considerations for Evaluation and Management of Bacterial Meningitis ||Download (.pdf)
Table 16–3. Key Considerations for Evaluation and Management of Bacterial Meningitis
Step 1: General assessment
- a) Assess vital signs and perfusion
- b) Establish vascular access
- c) Does the patient need cranial imaging?
Step 2: Laboratory studies
- a) Blood should be sent for complete cell count and culture
- b) Consider blood for electrolytes, blood urea nitrogen, creatinine, and glucose
- c) Cerebrospinal fluid should be obtained and sent for:
- Gram stain
- Bacterial culture
- Cell count and differential
- Glucose and protein
- Consider sending CSF for viral studies, such as enteroviral and/or herpes simplex PCR
- Consider sending CSF for fungal or mycobacterial studies
- d) Consider sending Lyme serology based on local epidemiology
Step 3: Treat infection
Step 4: Subsequent management
- a) Follow neurologic examination closely, especially cranial nerves
- b) Daily weights and strict measurement of intake and output
- c) Formal hearing evaluation
- d) Consider long-term follow-up including neuropsychiatric testing
It should be noted that it may not be possible to safely perform a lumbar puncture and the diagnosis will need to be a presumptive one in some patients. The lumbar puncture may need to be deferred if there are concerns of clinical instability, significantly elevated intracranial pressure (bradycardia, hypertension, irregular respirations, papilledema), or concern for intracranial lesion. The presence of thrombocytopenia (≤50,000 platelets/mm3) should prompt consideration for platelet transfusion prior to lumbar puncture. The presence of skin infection in the area overlying lumbar puncture should also be considered a relative contraindication because of the concern for inoculating bacteria from the skin site to the CSF.
The decision to perform a lumbar puncture should not rest on the results of blood testing. Among infants, a very low or high peripheral WBC does increase the risk for bacterial meningitis but 41% will have peripheral WBC values in the normal range.19 A negative peripheral blood culture does not rule out bacterial meningitis. Among patients with confirmed bacterial meningitis, no bacterial growth is seen in blood cultures in approximately one-third of cases.13,14,18–20 Despite these limitations, blood should be routinely obtained for culture from patients evaluated for suspected meningitis. A positive blood culture will influence the choice of antimicrobial therapy in cases where the CSF does not yield growth of a pathogen. Serologic tests may be helpful and Lyme serology should be routinely ordered in the proper epidemiologic setting (e.g., areas where infection is common, opportunity for exposure).
Neuroimaging does not need to be routinely ordered but should be performed during the course of therapy when patients experience unexplained changes in mental status, focal neurologic deficits, or there is other reason for concern of intracranial abscess, empyema, hemorrhage, infarct, or thrombosis.