Acute community-acquired bacterial meningitis in adults: An evidence-based review
ABSTRACTCommunity-acquired bacterial meningitis is still a significant cause of morbidity and mortality. Clinicians should know how to quickly diagnose it, perform a lumbar puncture, order the necessary tests, and start appropriate empiric therapy promptly.
KEY POINTS
- The most common organisms that cause community-acquired bacterial meningitis are Streptococcus pneumoniae and Neisseria meningitidis. The incidence of Listeria infection increases in patients over age 50 and in those with compromised cell-mediated immunity.
- Symptoms and signs are not sensitive or specific enough to diagnose community-acquired bacterial meningitis. A lumbar puncture for cerebrospinal fluid studies is needed to reach the diagnosis, to identify the organism, and to determine antimicrobial susceptibilities.
- Gram stain of cerebrospinal fluid may quickly identify the causative organism. It is not very sensitive, but it is specific.
- Lumbar puncture should be performed as soon as possible. Computed tomography of the head is not necessary in all patients, only in immunocompromised patients and those who have features suggestive of or who are at risk of increased intracranial pressure.
- Try to obtain blood and cerebrospinal fluid cultures before staring antimicrobial therapy, but do not delay therapy if obtaining them is not feasible.
MANAGEMENT
Empiric antimicrobial therapy must be started as soon as feasible
Most studies of the timing of antimicrobial drugs were retrospective and included a very heterogeneous population. They were thus more prone to bias and confounding.23,24 Proulx et al,23 in a retrospective study, found that if antibiotics were given within 6 hours of the time the patient presented to the emergency department, the case fatality rate was only 5% to 6%. If treatment started 6 to 8 hours after presentation, the death rate was 45%, and if it started from 8 to 10 hours after presentation, the death rate was 75%. Most physicians would agree that starting antimicrobials early would be beneficial.
CSF concentrations of most antimicrobial drugs are considerably less than in the serum due to poor penetration of the blood-CSF barrier. Thus, the dose for treating meningitis is usually higher than the regular dose. For example, for the treatment of pneumococcal pneumonia, ceftriaxone (Rocephin) is used at a dose of 1 g every 24 hours, but for pneumococcal meningitis the dose is 2 g every 12 hours.
Empiric treatment of community-acquired bacterial meningitis in immunocompetent adults up to 50 years of age consists of a third-generation cephalosporin such as cefotaxime (Claforan) 2 g intravenously every 4 hours or ceftriaxone 2 g intravenously every 12 hours, which covers most S pneumoniae and N meningitides strains.19 The IDSA guidelines recommend adding vancomycin (Vancocin) empirically in suspected S pneumoniae meningitis due to concerns about drug-resistant pneumococcal strains.19 For vancomycin, 45 to 60 mg/kg intravenously per day divided into every-6-hour or every-8-hour doses would achieve better CSF concentrations.25
In patients over age 50 or those with a cell-mediated immunodeficiency, empiric therapy should also include ampicillin 2 g intravenously every 4 hours to cover Listeria.
It is important to tailor therapy to the results of Gram stain, culture, and susceptibility as they become available.
Role of corticosteroids
Glucocorticoids, especially dexamethasone (Decadron), have been well studied as adjunctive therapies in bacterial meningitis. The rationale behind their use is that the profuse inflammatory response to the bacterial components in the CSF by itself has deleterious effects, and steroids can reduce that.
In 2004, a Cochrane meta-analysis26 of five randomized clinical trials, including 623 adults with bacterial meningitis (234 with pneumococcal meningitis and 232 with meningococcal meningitis), found a significant reduction in the death rate for patients who received steroids: the death rate was 12% in patients who received steroids vs 22% in those who did not (odds ratio 0.6; 95% CI 0.40–0.81). This led to an IDSA practice guideline recommendation that in adults with suspected or proven pneumococcal meningitis, dexamethasone would be beneficial.19
But since then, many more studies have emerged from Europe, South America, Malawi, and Vietnam, and another Cochrane metaanalysis27 incorporated the new studies. Twenty-four studies involving 4,041 participants were included. Similar numbers of participants died in the corticosteroid and placebo groups (18% vs 20%; risk ratio [RR] 0.92, 95% CI 0.82–1.04, P = .18). A trend towards a lower mortality rate was noticed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53–1.05, P = .09). In adults, corticosteroids were associated with lower rates of hearing loss (RR 0.74, 95% CI 0.56–0.98), and there was a trend towards fewer neurologic sequelae (RR 0.72, 95% CI 0.51–1.01). The benefits were shown in studies in adults in high-income countries, but the studies from low-income countries showed neither harm nor benefit. Based on these findings, the authors recommended the use of steroids in high-income countries, though the strength of the evidence was not optimal. The recommended steroid was dexamethasone 0.15 mg/kg intravenously every 6 hours for 4 days.
