Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis

Antibiotic therapy for suspected acute bacterial meningitis (ABM) needs to be started immediately, even before the results of cerebrospinal fluid culture and antibiotic sensitivity are available. It is not clear whether the available evidence supports the choice of third generation cephalosporins over the conventional antibiotic combination of ampicillin and chloramphenicol. Immediate institution of effective treatment through intravenous route may reduce death and disability in survivors.

The objective of this review is to determine the effectiveness and safety of the third generation cephalosporins and conventional treatment with penicillin/ampicillin-chloramphenicol in patients with community-acquired acute bacterial meningitis.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003) which contains the Cochrane Acute Respiratory Infections Group trials register, MEDLINE (January 1966 to November 2003), and EMBASE (January 1990 to November 2003). We also searched the reference list of review articles and textbook chapters and contacted experts for any unpublished trials.

Randomised controlled trials comparing ceftriaxone or cefotaxime with conventional antibiotics as empirical therapy of acute bacterial meningitis.

Two independent reviewers applied the study selection criteria, assessed methodological quality and extracted data.

Eighteen trials included 993 patients in the analysis. The kappa (chance-corrected agreement) between the observers in study selection and data extraction was substantial. There was no heterogeneity of results among the studies in any outcome except diarrhoea. There was no statistically significant difference between the groups in the risk of death (risk difference -1%; 95% confidence interval (CI) -4% to +3%), risk of deafness (risk difference -4%; 95% CI -9% to +1%), risk of treatment failure (risk difference -2%; 95% CI -5% to +2%). However, there were significantly decreased risk of culture positivity of CSF after 10-48 hours (risk difference -6%; 95% CI -11% to 0%) and statistically significant increased in the risk of diarrhoea between the groups (risk difference +8%; 95% CI +3% to +13%) with the third generation cephalosporins. The risk of neutropenia and skin rash were not significantly different between the two groups. However, all the studies have been conducted in the eighties except two, which have been conducted in 1993 and 1996.

Although the review shows no clinically important difference between ceftriaxone or cefotaxime and conventional antibiotics, the studies are done decades ago and may not apply to current routine practice. However, in situations where ceftriaxone or cefotaxime are not available or affordable, ampicillin-chloramphenicol combination may be used as an alternative. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in developing as well as developed countries. The factors determining overuse of antibiotics in developing countries and educational interventions to limit such practice are priority area for research in developing countries.