{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:56:29Z","timestamp":1790218589454,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background: The antibiotic ibezapolstat and the live biotherapeutic product live-JSLM are promising future approaches for treating Clostridioides difficile infection. Ibezapostat is a highly specific antibiotic for Clostridioides difficile, with minimal impact on the intestinal flora. Live-JSLM is designed to restore healthy intestinal microbiota, thus preventing recurrence of Clostridioides difficile infection. In this narrative review, we reviewed available data on ibezapostat and live-JSLM, considering that they are prototypes of two distinct, unique mechanisms of action against Clostridioides difficile. Methods: Data sources: PubMed and SCOPUS databases were searched from 1 January 2012 to 15 November 2025. Original articles reporting data on ibezapolstat and live-JSLM were included. Results: 31 studies were included. When compared to conventional anti-Clostridioides difficile antibiotics, ibezapolstat had a similar level of effectiveness and minimal impact on the gut microbiota. The available data confirm live-JSLM safety and efficacy in restoring the gut microbiota following the conclusion of the standard anti-Clostridioides difficile antibiotic regimen. Conclusions: The results on ibezapolstat efficacy are promising, but require confirmation in larger patient populations through double-blind, randomised phase III trials. In the near future, an integrated approach may enhance the management of Clostridioides difficile infection: starting with highly specific antibiotics, i.e., ibezapolstat, followed by microbiome-based therapies such as live-JSLM.<\/jats:p>","DOI":"10.3390\/idr18020034","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Newer Therapeutics to Selectively Kill Clostridioides difficile and Restore the Microbiome"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-0545","authenticated-orcid":false,"given":"Guido","family":"Granata","sequence":"first","affiliation":[{"name":"Systemic and Immune Depression-Associated Infection Unit, National Institute for Infectious Diseases \u201cL. Spallanzani\u201d, I.R.C.C.S., 00149 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-7567","authenticated-orcid":false,"given":"Nicola","family":"Petrosillo","sequence":"additional","affiliation":[{"name":"Infectious Disease Service, Fondazione Policlinico Universitario Campus Bio-Medico, 00127 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. 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