{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:07Z","timestamp":1785430447358,"version":"3.56.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Beijing Public Health Experts Project","award":["G2023-3-004"],"award-info":[{"award-number":["G2023-3-004"]}]},{"name":"Outstanding Young Scientific and Technological Workers in Tongzhou District","award":["JCQN2023011"],"award-info":[{"award-number":["JCQN2023011"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Multidrug-resistant tuberculosis (MDR-TB) is often associated with poor clinical outcomes. This study evaluated the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of lefamulin (LEF) and intracellular activities against\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      . In this study, we evaluated the potential of LEF as a new drug candidate for treating\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      infections, including MDR-TB. The antimicrobial susceptibility testing was performed to determine the minimum inhibitory concentrations (MICs) of LEF against 132 clinical isolates of\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      . The intracellular activity of LEF and its interaction with other anti-tuberculosis drugs were also evaluated using\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      H37Rv. From the 132\n                      <jats:italic toggle=\"yes\">M<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">tuberculosis<\/jats:italic>\n                      clinical isolates\n                      <jats:italic toggle=\"yes\">,<\/jats:italic>\n                      the MIC\n                      <jats:sub>50<\/jats:sub>\n                      and MIC\n                      <jats:sub>90<\/jats:sub>\n                      were 0.5 \u00b5g\/mL and 1 \u00b5g\/mL, respectively. The tentative epidemiological cut-off (ECOFF) against LEF was defined at 1 \u00b5g\/mL. After 5 days of incubation, LEF at 2 \u00b5g\/mL inhibited 89.88% \u00b1 1.73% of intracellular bacterial growth, which was comparable with the inhibitory rate of 94.29% \u00b1 1.32% achieved by INH at 2 \u00b5g\/mL. In addition, a synergy between LEF and bedaquiline (BDQ) was observed with a fractional inhibitory concentration index = 0.5. Furthermore, LEF showed no correlation with resistance to 10 anti-tuberculosis drugs. The minimum bactericidal concentration\/MIC of LEF values suggested that it is a bacteriostatic drug against\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      , and the bactericidal activity is mainly characterized by a concentration-dependent pattern. LEF has potent inhibitory activities against\n                      <jats:italic toggle=\"yes\">M. tuberculosis in vitro<\/jats:italic>\n                      as well as in macrophages. Furthermore, the synergistic effect with BDQ also favors LEF as a promising drug candidate for tuberculosis treatment, especially for MDR-TB.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Lefamulin (LEF), the first systemic pleuromutilin antibiotic approved for human use, exhibits broad-spectrum activity against Gram-positive bacteria. However, its\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        activity against\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        (\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        ) remains unexplored. This study evaluated the potential of LEF for treating\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        infections, including multidrug-resistant tuberculosis. Our findings demonstrate that LEF possesses potent bacteriostatic activity against\n                        <jats:italic toggle=\"yes\">Mtb in vitro<\/jats:italic>\n                        and exhibits synergistic effects when combined with bedaquiline. These results suggest LEF as a promising therapeutic candidate for tuberculosis treatment.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02250-25","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:48:31Z","timestamp":1759920511000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Lefamulin harbors promising anti-tuberculosis activity against multidrug-resistant\n                    <i>Mycobacterium tuberculosis<\/i>\n                    isolates"],"prefix":"10.1128","volume":"13","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfei","family":"Ji","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihe","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Dong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-7321","authenticated-orcid":true,"given":"Xia","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2024","author":"World Health Organization","year":"2024","unstructured":"World Health Organization. 2024. 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