Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis.

BACKGROUND: Antibiotic therapy for suspected acute bacterial meningitis (ABM) needs to be started immediately, even before the results of cerebrospinal fluid (CSF) culture and antibiotic sensitivity are available. Immediate commencement of effective treatment using the intravenous route may reduce death and disability. Although bacterial meningitis guidelines advise the use of third generation cephalosporins, these drugs are often not available in hospitals in low income countries.
OBJECTIVES: The objective of this review was to compare the effectiveness and safety of third generation cephalosporins and conventional treatment with penicillin or ampicillin-chloramphenicol in patients with community-acquired ABM. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1) which contains the Cochrane Acute Respiratory Infections Group Trials Register, MEDLINE (January 1966 to March 2007), and EMBASE (January 1974 to March 2007). We also searched the reference list of review articles and book chapters, and contacted experts for any unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ceftriaxone or cefotaxime with conventional antibiotics as empirical therapy for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed methodological quality, and extracted data. MAIN
RESULTS: Nineteen trials that involved 1496 patients were included in the analysis. 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 (RD) 0%; 95% confidence interval (CI) -3% to 2%), risk of deafness (RD -4%; 95% CI -9% to 1%), or risk of treatment failure (RD -1%; 95% CI -4% to 2%). However, there were significantly decreased risks of culture positivity of CSF after 10 to 48 hours (RD -6%; 95% CI -11% to 0%) and statistically significant increases in the risk of diarrhoea between the groups (RD 8%; 95% CI 3% to 13%) with the third generation cephalosporins. The risk of neutropaenia and skin rash were not significantly different between the two groups. However, all the studies were conducted in the 1980s except three, which were reported in 1993, 1996, and 2005. AUTHORS'
CONCLUSIONS: The review shows no clinically important difference between ceftriaxone or cefotaxime and conventional antibiotics. In situations where availability or affordability is an issue, third generation cephalosporins, ampicillin-chloramphenicol combination, or chloramphenicol alone may be used as alternatives. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in low to middle income countries as well as high income countries.