Antibiotics for preventing leptospirosis

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Abstract
Leptospirosis is an infectious disease transmitted by animals. Death occurs in about five per cent of the patients. In clinical practice, doxycycline is widely used for prevention. To evaluate the effectiveness and safety of any antibiotic regimen versus placebo or other antibiotic regimens in the prophylaxis of leptospirosis. The sources used were: EMBASE, LILACS, MEDLINE, SCISEARCH, The Cochrane Controlled Trials Register, The Cochrane Hepato‐Biliary Group Controlled Trials Register, bibliographies of published papers, and personal communication with authors. There were no language or date restrictions in any of the searches. STUDIES: All randomised clinical trials in which antibiotics were used as prophylactic regimen for leptospirosis. PARTICIPANTS: People potentially exposed to leptospirosis, such as people in endemic areas during the rainy season, health professionals and other professionals with high risk of infection. INTERVENTION: Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen). OUTCOMES: Infection (primary outcome) and adverse events (secondary outcome). Data were independently extracted and methodological quality of each trial was assessed by two reviewers as well as cross‐checked. Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow‐up were recorded. The results of each trial were summarised on an intention‐to‐treat basis in 2 x 2 tables for each outcome. Two trials comparing doxycycline with placebo met the inclusion criteria. We did not find trials comparing doxycycline versus other antibiotics, or other antibiotics versus placebo. One of the trials had excellent methodological quality. In the other trial, the allocation concealment process, generation of allocation sequence, and blinding methods were not described. Of the 1022 participants enrolled, 509 were treated with doxycycline and 513 with placebo. Of these, 940 participants were soldiers included in one trial. The patients assigned to the antibiotics group compared with the ones assigned to the placebo group showed: Symptomatic, verified leptospirosis: 0.6% (3/509) versus 4.9% (25/ 513); risk difference (random effects model) ‐4.1%, 95% confidence interval ‐5.9% to ‐2.3%. Number needed‐to‐treat 24 (95% confidence interval 17 to 43). Adverse effects: 3% (13/469 participants) versus 0.2% (1/471 participants); random effects model 2.6%, 95% confidence interval 1.0% to 4.1%. Number needed‐to‐harm 39 (95% confidence interval 25 to 100). Prophylaxis of leptospirosis may be achieved by administration of doxycycline to soldiers training in endemic areas with a high risk of exposure to leptospirosis. Whether these findings apply to other scenarios or not remains to be proven.