{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:45:41Z","timestamp":1789469141748,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Microbiol Infect Dis"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence of multi-drug resistant tuberculosis (MDR-TB) and the challenges of novel drug discovery for the treatment of drug-susceptible and drug-resistant strains of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . Rifampicin is a key first-line TB drug and rifampicin resistance is a major obstacle to treating MDR-TB. Utilising existing antimicrobial drugs to supplement combination therapy and overcome rifampicin resistance is a promising solution due to their widespread availability and proven clinical safety profile. Therefore, this study aimed to explore the feasibility of using beta-lactam\/beta-lactamase inhibitor combinations with rifampicin to inhibit the growth of multidrug-resistant\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . Based on inhibitory concentration (IC), oral bioavailability, pricing, commercial availability, five beta-lactams and the beta-lactamase inhibitor, clavulanate, were selected for testing. These were combined with rifampicin for in vitro testing against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    H37Rv. Resazurin assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index (DRI). The combination of tebipenem-clavulanate\/rifampicin and cephradine-clavulanate\/rifampicin were found to be synergistic and highly effective against clinical isolates of MDR-TB, overcoming rifampicin resistance in vitro. Beta-lactam synergy may provide viable combination therapies with rifampicin to address the issue of drug resistance in TB.\n                  <\/jats:p>","DOI":"10.1007\/s10096-025-05062-3","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T05:11:02Z","timestamp":1741237862000},"page":"1279-1284","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Beta-lactam combination treatment overcomes rifampicin resistance in Mycobacterium tuberculosis"],"prefix":"10.1007","volume":"44","author":[{"given":"Diana H.","family":"Quan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trixie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna Y.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitali","family":"Sintchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warwick J.","family":"Britton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Triccas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem","family":"Alffenaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"5062_CR1","volume-title":"Global tuberculosis Report 2023","author":"WHO","year":"2023","unstructured":"WHO (2023) Global tuberculosis Report 2023. 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