{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T02:16:22Z","timestamp":1776824182644,"version":"3.51.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","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:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["KANT23G0"],"award-info":[{"award-number":["KANT23G0"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NTM Education and Research"},{"DOI":"10.13039\/100016048","name":"University of Texas at Tyler","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In patients with Mycobacterium abscessus (MAB) lung disease (LD), guideline-based therapy (GBT) achieves sputum culture conversion in only 20\u201335% of patients. The poor efficacy is reflected in the hollow fibre model system for MAB-LD (HFS-MAB), where GBT drugs\u2019 maximal microbial kill (Emax) below day 0 burden (B0) were amikacin 3 colony-forming units (cfu)\/mL, clarithromycin\u2013cefoxitin\u2013amikacin (GBT) 17\u2005cfu\/mL, imipenem 20\u2005cfu\/mL, and tigecycline 24\u2005cfu\/mL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested the bacterial leucyl-tRNA synthetase (LeuRS) inhibitor, epetraborole, for MICs in 59 MAB isolates, and with seven epetraborole exposures in the HFS-MAB over 21\u2005days. Data were analysed using the inhibitory sigmoid Emax model for microbial kill, and a quadratic function for resistance. Monte Carlo experiments (MCE) were performed to identify the optimal epetraborole dose for the clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The epetraborole MIC50 was 0.125\u2005mg\/L, and the MIC90 was 0.25\u2005mg\/L. Epetraborole killed 253\u2005cfu\/mL below B0. However, epetraborole microbial effect was terminated by antimicrobial resistance, in an exposure-dependent fashion. Whole genome sequencing revealed concentration-dependent generation of resistance-associated LeuRS mutations, including novel mutations such as Asp433Val, Arg324Ser, and Phe310Cys. The exposure mediating 80% of Emax (EC80) was an AUC0\u201324\/MIC\u200a=\u200a202.73. In MCE 750\u2005mg twice daily achieved EC80 in 95.6% and 79.2% of virtual patients for intravenous versus oral administration, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Epetraborole microbial kill is the best, thus far, achieved in the HFS-MAB, more than two times omadacycline\u2019s 123\u2005cfu\/mL below B0. We propose to test a novel combination regimen of epetraborole plus omadacycline plus a \u03b2-lactam versus GBT first in the HFS-MAB, followed by clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf405","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T13:50:27Z","timestamp":1760449827000},"source":"Crossref","is-referenced-by-count":3,"title":["Preclinical evaluation of epetraborole in the hollow fibre system model of\n                    <i>Mycobacterium abscessus<\/i>\n                    lung disease"],"prefix":"10.1093","volume":"81","author":[{"given":"Sanjay","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler , Tyler, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunavanthi D","family":"Boorgula","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler , Tyler, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-7362","authenticated-orcid":false,"given":"Minh-Vu H","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, University of California, Davis Health , Sacramento, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles L","family":"Daley","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado, and University of Colorado , Aurora, CO ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-8012","authenticated-orcid":false,"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"Hollow Fiber System & Experimental Therapeutics Laboratories, Wet Lab Systems, Praedicare Inc. , Dallas, TX ,","place":["USA"]},{"name":"Impi Biotech Consortium Inc. , Mount Hampden ,","place":["Zimbabwe"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-8851","authenticated-orcid":false,"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler , Tyler, TX ,","place":["USA"]},{"name":"Department of Cellular and Molecular Biology, University of Texas Health Science Centre at Tyler , Tyler, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"2026011413272205400_dkaf405-B1","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/ciaa241","article-title":"Treatment of nontuberculous mycobacterial 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