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.

Updated ACVIM consensus statement on leptospirosis in dogs

“…Based on the marked morbidity and potential mortality of the disease, and the risk of zoonotic transmission, as recommended for humans by the CDC, 120 dogs with suspected or probable leptospirosis should be treated with appropriate antimicrobials (LOA 12/12) , despite lack of evidence for a clear benefit for affected humans 121 . The optimal antimicrobial treatment for leptospirosis is unknown.…”

Current treatment options for leptospirosis: a mini-review

“…Patients with severe leptospirosis, which normally manifests as renal and hepatic failure, are administered penicillin G (penicillin G sodium; at a dose of 1.5 million U/6 h) intravenously ( Figure 1 ). It should be used for a week ( Watt et al, 1988 ; Griffith et al, 2006 ; Karpagam and Ganesh, 2020 ; Guzmán Pérez et al, 2021 ). In accordance with reported records, amoxicillin, ampicillin, azithromycin, doxycycline and tetracycline can also be used for the treatment of severe leptospirosis.…”

“…In accordance with reported records, amoxicillin, ampicillin, azithromycin, doxycycline and tetracycline can also be used for the treatment of severe leptospirosis. It is recommended that children and pregnant women avoid the consumption of doxycycline ( Griffith et al, 2006 ; Jamal Khan et al, 2018 ; Gopi et al, 2021 ; Guzmán Pérez et al, 2021 ). Amoxicillin and azithromycin should be administered to children and pregnant women instead of doxycycline ( Haake and Levett, 2015 ; Karpagam and Ganesh, 2020 ; Chacko et al, 2021 ).…”

Antibacterial Activity of Crude Momordica charantia, Cassia alata, and Allium sativum Methanolic Extracts on Leptospira interrogans serovar Manilae

“…1 However, studies have found insufficient evidence to show the benefit of using these antibiotics in leptospirosis management, especially in severe disease and disease prevention. 4,5 One meta-analysis of clinical trials showed that penicillin is not significantly different from placebo in reducing mortality or length of hospital stay when used to treat leptospirosis infections. 5 The same study looked into clinical trials on chemoprophylaxis and found that while there was a significant benefit for taking doxycycline upon flood water exposure, none of the usual antibiotic regimens against leptospirosis were beneficial in reducing symptomatic cases.…”

“…4,5 One meta-analysis of clinical trials showed that penicillin is not significantly different from placebo in reducing mortality or length of hospital stay when used to treat leptospirosis infections. 5 The same study looked into clinical trials on chemoprophylaxis and found that while there was a significant benefit for taking doxycycline upon flood water exposure, none of the usual antibiotic regimens against leptospirosis were beneficial in reducing symptomatic cases. 5 Another systematic review of clinical trials concluded that based on data on mortality, duration of illness, duration of fever, and need for dialysis, the benefit of currently used antibiotics in treating leptospirosis is unclear.…”