Antibiotic prophylaxis for leptospirosis

Tabei, Kozue; Win, Tin Zar; Kitashoji, Emi; Brett-Major, David M.; Edwards, Tansy; Smith, Chris; Mukadi, Patrick

doi:10.1002/14651858.cd014959

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…The use of antibiotics for leptospirosis may decrease the duration of clinical illness by 2–4 days, although this result was not statistically significant . The efficacy of treatment with antibiotics such as penicillin, doxycycline, azithromycin, or cephalosporins, commonly found in leptospirosis treatment regimes, did not seem to impact mortality or the duration of the fever. , Therefore, it was concluded that antibiotic therapy’s benefit in treating leptospirosis remains unclear, particularly for severe diseases . Therefore, antibiotics may not be used for mild cases in low-risk people.…”

Section: Introductionmentioning

confidence: 99%

A New Beginning to the Existing Medicines; Repurposing FDA-Approved Drugs for the Neglected Re-Emerging Disease Leptospirosis

Christie,

Hariharan,

Chakraborti

et al. 2024

ACS Omega

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Leptospirosis is one of the re-emerging zoonotic diseases, especially in tropical regions. Many antibiotics are used to treat leptospirosis, but there are no scientific evidence-based guidelines or systematic clinical trials for using these drugs. A bioinformatics approach was made to shortlist some Food and Drug Administration (FDA) of the United States of Americaapproved and currently used drugs for leptospirosis. The existing drugs from the Drug Bank database, which are currently not used for leptospirosis, were selected to identify their target proteins and binding sites using bioinformatics methods. Orthologues of these target proteins were selected from the proteome database of Leptospira. The similar sites and their interactions with the drugs were validated and recommended for use in leptospirosis. Further, the sensitivity of recommended drugs was also validated in vitro. The sequences and structures of these proteins were compared under strictly controlled parameters and shortlisted Gatifloxacin, Imipenem, Latamoxef, Doripenem, Tigecycline, and Lactams as repurposable drugs for leptospirosis. An in vitro validation of the drugs showed significant antileptospiral activity in 12 serovars with low IC 50 concentrations and also showed that the IC 50 values varied across Leptospira serovars. Further, suitable proteins under the concept of "One Target, Many Drugs" identified DNA gyrase subunit A (Q72WD1), 30S ribosomal protein S9 (Q72U99), and 30S ribosomal protein S12 (Q72UA6), and these proteins were found across the pathogenic, saprophytic, and intermediate species of Leptospira. We describe a method to find repurposable drugs from the approved list that are not currently used to treat leptospirosis and validate them to be taken forward for systematic clinical trials specific to leptospirosis for recommendations in clinical use.

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