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With no current FDA-approved treatment and cure rates &lt;50%, there is a pressing need for effective therapies. Here we report T405, a new \u03b2-lactam of the penem subclass that exhibits potent activity against <jats:italic>M. abscessus<\/jats:italic> and a panel of drug-resistant strains isolated from cystic fibrosis patients. Additionally, in combination with the \u03b2-lactamase inhibitor avibactam, the rate of spontaneous resistance of <jats:italic>M. abscessus<\/jats:italic> to T405 approached the limit of detection. Lastly, we show the favorable pharmacokinetic profile of T405 in mice and the absence of toxicity at elevated dosage, which support the clinical potential of this compound.<\/jats:p>","DOI":"10.1038\/s42003-020-01475-2","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T11:07:06Z","timestamp":1607339226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Development of a penem antibiotic against Mycobacteroides abscessus"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7367-5568","authenticated-orcid":false,"given":"Hunter R.","family":"Batchelder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Story-Roller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6984-7400","authenticated-orcid":false,"given":"Evan P.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-1721","authenticated-orcid":false,"given":"Amit","family":"Kaushik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M.","family":"Bigelow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Maggioncalda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Nuermberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0114","authenticated-orcid":false,"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-7585","authenticated-orcid":false,"given":"Craig A.","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"1475_CR1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","volume":"175","author":"DE Griffith","year":"2007","unstructured":"Griffith, D. 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