Preventive antibiotics for infections in acute stroke: A systematic review and meta-analysis

Objective: To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke. Data Sources: The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles. Study Selection: Randomized controlled trials on preventive antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded. Data Extraction: Each study was scored for methodological key issues and appraised by the Jadad scale. We extracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis. Data Synthesis: We identified 4 randomized clinical trials including 426 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tetracycline or a combination of β-lactam antibiotic with β-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of therapy varied between 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infection was significantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was reported. Conclusions: In adults with acute stroke, preventive antibiotics reduced the risk of infection, but did not reduce mortality. The observed effect warrants evaluation of preventive antibiotics in large stroke trials.