Current Evidence on the Antimicrobial Treatment and Chemoprophylaxis of Human Leptospirosis: A Meta-Analysis

Abstract

Background: Leptospirosis is a worldwide zoonotic infection, and its management needs to be refined. This study aims to discern which antibiotic would be the best option to treat leptospirosis disease and analyze the efficacy of chemoprophylaxis regimens to prevent this illness. Methods: systematic review and meta-analysis on the efficacy of antibiotic treatment and chemoprophylaxis of leptospirosis in humans. Results: Ten clinical trials compared an antibiotic treatment with placebo or other antibiotic treatments in leptospirosis (the most recent one was published in 2007). The meta-analysis shows no effect of penicillin treatment on mortality compared to placebo (OR 1.65; 95% CI 0.76–3.57; p = 0.21). There are no differences between penicillin and cephalosporins or doxycycline. Penicillin does not reduce the time of defervescence (MD-0.16; 95% CI (−1.4) –1.08; p = 0.80) nor hospital stay (MD 0.15; 95% CI (−0.75)–1.06; p = 0.74). Besides, the data did not demonstrate any effectiveness of the use of penicillin in terms of the incidence of oliguria/anuria, the need for dialysis treatment, time to creatinine normalization, incidence of jaundice, or the liver function normalization time. Eight trials have assessed prophylactic treatment against leptospirosis with different strategies. A weekly dose of 200 mg of doxycycline does not show benefit versus placebo regarding the number of new cases of symptomatic leptospirosis (OR 0.20; 95% CI 0.02–1.87; p = 0.16). A single dose of doxycycline at exposure to flood water could have a beneficial effect (OR 0.23; 95% CI 0.07–0.77; p = 0.02). None of the other chemoprophylaxis regimens tested have shown a statistically significant effect on the number of new symptomatic cases. Conclusion: There is no evidence that antibiotics are a better treatment than placebo regarding mortality, shortening of fever, liver and kidney function, or reduction in the hospital stay. On the other hand, neither doxycycline nor penicillin, nor azithromycin have shown statistically significant differences in preventing symptomatic infection. Well-designed clinical trials, including other antibiotics such as quinolones or aminoglycosides, are urgently needed to improve our understanding of the treatment for this infection, which continues to be a neglected disease.