Newer Therapeutics to Selectively Kill <em>Clostridioides difficile </em>and Restore the Microbiome

Background/ Objectives: The antibiotic ibezapolstat and the live biotherapeutic product live-JSLM are promising future approaches for treating Clostridioides difficile infection. We summarised the available data on ibezapolstat and live-JSLM to treat Clostridioides difficile infection.Methods: Data sources: PubMed and SCOPUS databases were searched from The MEDLINE and SCOPUS databases from 1 January 2012 to 15 November 2025. Original articles reporting data on ibezapolstat and live-JSLM. Both quantitative and qualitative information were summarised by means of textual descriptions. Results: 32 studies were included, published from 15 March 2012 to 15 September 2025. When compared to conventional anti-Clostridioides difficile antibiotics ibezapolstat had 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. Discussion: The results on ibezapolstat efficacy are promising, but require confirmation in larger patient populations through double-blind, randomized 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.