Efficacy and safety of chloramphenicol: joining the revival of old antibiotics? Systematic review and meta-analysis of randomized controlled trials

Objectives: Chloramphenicol is an old broad-spectrum antibiotic. We assessed its efficacy and safety. Methods: This was a systematic review and meta-analysis. Electronic databases were searched to identify randomized controlled trials (RCTs) that assessed patients, of any age, with systemic bacterial infections that can cause sepsis and compared chloramphenicol alone versus other antibiotics. No restrictions on the date of publication, language or publication status were applied. The primary outcome assessed was overall mortality. Results: Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00-1.97] and meningitis (RR 1.27, 95% CI 1.00-1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07-2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07-3.2). Therewere no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65-4.75, I-2 = 0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46-0.99, I-2 = 0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results. Conclusions: Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses. RCTs are needed to test this treatment against MDR organisms when better alternatives do not exist.