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A Systematic Review and Meta-analysis

Diederik van de Beek, MD, PhD; Eelco F. M. Wijdicks, MD, PhD; Frederique H. Vermeij, MD; Rob J. de Haan, PhD; Jan M. Prins, MD, PhD; Lodewijk Spanjaard, MD, PhD; Diederik W. J. Dippel, MD, PhD; Paul J. Nederkoorn, MD, PhD

Arch Neurol. 2009;66(9):1076-1081.

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.

Author Affiliations: Departments of Neurology (Drs van de Beek and Nederkoom), Clinical Epidemiology and Biostatistics (Dr de Haan), Infectious Diseases (Dr Prins), and Medical Microbiology (Dr Spanjaard), Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology, Division of Critical Care Neurology, Mayo Clinic, Rochester, Minnesota (Dr Wijdicks); and the Department of Neurology (Drs Vermeij and Dippel), Erasmus University Medical Center, Rotterdam, the Netherlands.

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