{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:34:01Z","timestamp":1789652041436,"version":"4.0.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Paratek Pharmaceuticals Inc"},{"name":"HHS | National Institutes of Health","award":["K23 AI159145"],"award-info":[{"award-number":["K23 AI159145"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,7,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Treatment outcomes for\n              <jats:italic>Mycobacteroides abscessus<\/jats:italic>\n              (\n              <jats:italic>Mab<\/jats:italic>\n              , also known as\n              <jats:italic>Mycobacterium abscessus<\/jats:italic>\n              ) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating\n              <jats:italic>Mab<\/jats:italic>\n              disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against\n              <jats:italic>Mab<\/jats:italic>\n              . Since any new antibiotic effective against\n              <jats:italic>Mab<\/jats:italic>\n              is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary\n              <jats:italic>Mab<\/jats:italic>\n              clinical isolates in a mouse model of\n              <jats:italic>Mab<\/jats:italic>\n              lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with\n              <jats:italic>Mab<\/jats:italic>\n              burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced\n              <jats:italic>Mab<\/jats:italic>\n              levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen\u2019s effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in\n              <jats:italic>Mab<\/jats:italic>\n              disease patients is needed to determine the most effective omadacycline-containing regimen.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>Mycobacteroides abscessus<\/jats:italic>\n                is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating\n                <jats:italic>M. abscessus<\/jats:italic>\n                disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against\n                <jats:italic>M. abscessus<\/jats:italic>\n                . Using a mouse model that mimics\n                <jats:italic>M. abscessus<\/jats:italic>\n                disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with\n                <jats:italic>M. abscessus<\/jats:italic>\n                patients is necessary to optimize omadacycline-based treatment strategies for this disease.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00381-24","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T13:00:58Z","timestamp":1720530058000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Efficacies of omadacycline + amikacin + imipenem and an all-oral regimen omadacycline + clofazimine + linezolid in a mouse model of\n            <i>M. abscessus<\/i>\n            lung disease"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4760-0172","authenticated-orcid":true,"given":"Elisa H.","family":"Ignatius","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Center for Nontuberculous Mycobacteria and Bronchiectasis, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binayak","family":"Rimal","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra M.","family":"Panthi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-6320","authenticated-orcid":true,"given":"Alisa W.","family":"Serio","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0114","authenticated-orcid":true,"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Center for Nontuberculous Mycobacteria and Bronchiectasis, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 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