{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:47:34Z","timestamp":1792205254168,"version":"4.4.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2019-05 901"],"award-info":[{"award-number":["2019-05 901"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    As meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant. Broth microdilution MICs were determined using the EUCAST reference method. Meropenem and tebipenem were tested individually and in combination with vaborbactam 8 mg\/L and clavulanic-acid 2 and 4 mg\/L, respectively. Whole-genome sequencing was performed to explore resistance mechanisms. Clavulanic acid lowered the modal tebipenem MIC approximately 16-fold (from 16 to 1 mg\/L). The modal meropenem MIC was reduced twofold by vaborbactam compared with an approximately eightfold decrease by clavulanic acid. The only previously described high-confidence carbapenem resistance mutation,\n                    <jats:italic toggle=\"yes\">crfA<\/jats:italic>\n                    T62A, was shared by a subgroup of lineage 4.3.4.1 isolates and did not correlate with elevated MICs. The presence of a \u03b2-lactamase inhibitor reduced the MTBC MICs of tebipenem and meropenem. The resulting MIC distribution was lowest for the orally available drugs tebipenem-clavulanic acid. Whether this\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    activity translates to similar or greater clinical efficacy of tebipenem-clavulanic acid compared with the currently WHO-endorsed meropenem-clavulanic acid requires clinical studies.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Repurposing of already approved antibiotics, such as \u03b2-lactams in combination with \u03b2-lactamase inhibitors, may provide new treatment alternatives for drug-resistant tuberculosis. Meropenem-clavulanic acid was more active\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      compared to meropenem-vaborbactam. Notably, tebipenem-clavulanic acid showed even better activity, raising the potential of an all-oral treatment option. Clinical data are needed to investigate whether the better\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of tebipenem-clavulanic acid correlates with greater clinical efficacy compared with the currently WHO-endorsed meropenem-clavulanic acid.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01781-23","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T09:03:06Z","timestamp":1695373386000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["<i>In vitro<\/i>\n                    activity of new combinations of \u03b2-lactam and \u03b2-lactamase inhibitors against the\n                    <i>Mycobacterium tuberculosis<\/i>\n                    complex"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6296-2522","authenticated-orcid":false,"given":"Elin","family":"Economou Lundeberg","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Central Hospital of Kristianstad","place":["Kristianstad, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Wijkander","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Public Health Agency of Sweden","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Groenheit","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Public Health Agency of Sweden","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-351X","authenticated-orcid":false,"given":"Mikael","family":"Mansj\u00f6","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Public Health Agency of Sweden","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Werngren","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Public Health Agency of Sweden","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Cortes","sequence":"additional","affiliation":[{"name":"Pathogen Gene Regulation Unit, Biomedicine Institute of Valencia (IBV), CSIC","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Barilar","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel","place":["Borstel, Germany"]},{"name":"German Center for Infection Research, Partner site Hamburg-Lu\u0308beck-Borstel-Riems","place":["Borstel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-0684","authenticated-orcid":false,"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel","place":["Borstel, Germany"]},{"name":"German Center for Infection Research, Partner site Hamburg-Lu\u0308beck-Borstel-Riems","place":["Borstel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Merker","sequence":"additional","affiliation":[{"name":"German Center for Infection Research, Partner site Hamburg-Lu\u0308beck-Borstel-Riems","place":["Borstel, Germany"]},{"name":"Evolution of the Resistome, Research Center Borstel","place":["Borstel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-846X","authenticated-orcid":false,"given":"Claudio U.","family":"K\u00f6ser","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-3320","authenticated-orcid":false,"given":"Lina","family":"Davies Forsman","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Karolinska University Hospital","place":["Stockholm, Sweden"]},{"name":"Department of Medicine, Division of Infectious Diseases, Karolinska Institutet","place":["Solna, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO . 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