{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T07:50:57Z","timestamp":1770018657960,"version":"3.49.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"MERCK, Inc","award":["53438"],"award-info":[{"award-number":["53438"]}]},{"DOI":"10.13039\/100015581","name":"Houston Methodist Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015581","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DK089507"],"award-info":[{"award-number":["DK089507"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Luke Hoffman and Rafael Hernandez"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tedizolid is a protein synthesis inhibitor in clinical use for the treatment of Gram-positive infections. Pulmonary MRSA infections are a growing problem in patients with cystic fibrosis (CF) and the efficacy of tedizolid-based therapy in CF pulmonary infections is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the in vitro and in vivo activity of tedizolid and predict the likelihood of tedizolid resistance selection in CF-background Staphylococcus aureus strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A collection of 330 S. aureus strains (from adult and paediatric patients), either of normal or small colony variant (SCV) phenotypes, gathered at three CF centres in the USA was used. Tedizolid activity was assessed by broth microdilution, Etest and time\u2013kill analysis. In vivo tedizolid efficacy was tested in a murine pneumonia model. Tedizolid in vitro mutants were obtained by 40\u2009days of exposure and progressive passages. Whole genome sequencing of clinical S. aureus strains with reduced susceptibility to tedizolid was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MRSA strain MIC90s were tedizolid 0.12\u20130.25\u2009mg\/L and linezolid 1\u20132\u2009mg\/L; for MSSA strains, MIC90s were tedizolid 0.12\u2009mg\/L and linezolid 1\u20132\u2009mg\/L. Two strains, WIS 441 and Seattle 106, with tedizolid MICs of 2\u2009mg\/L and 1\u2009mg\/L, respectively, had MICs above the FDA tedizolid breakpoint (0.5\u2009mg\/L). Tedizolid at free serum concentrations exhibited a bacteriostatic effect. Mean bacterial burdens in lungs (log10\u2009cfu\/g) for WIS 423-infected mice were: control, 11.2\u00b10.5; tedizolid-treated (10\u2009mg\/kg), 3.40\u00b11.87; linezolid-treated (40\u2009mg\/kg), 4.51\u00b12.1; and vancomycin-treated (30\u2009mg\/kg), 5.21\u00b11.93. For WIS 441-infected mice the (log10\u2009cfu\/g) values were: control, 9.66\u00b10.8; tedizolid-treated, 3.18\u00b11.35; linezolid-treated 5.94\u00b12.19; and vancomycin-treated, 4.35\u00b11.7.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results suggest that tedizolid represents a promising therapeutic option for the treatment of CF-associated MRSA\/MSSA infections, having potent in vivo activity and low resistance potential.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz418","type":"journal-article","created":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T11:42:56Z","timestamp":1568374976000},"page":"126-134","source":"Crossref","is-referenced-by-count":16,"title":["Tedizolid is a promising antimicrobial option for the treatment of <i>Staphylococcus aureus<\/i> infections in cystic fibrosis patients"],"prefix":"10.1093","volume":"75","author":[{"given":"Melanie","family":"Roch","sequence":"first","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Celeste","family":"Varela","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agustina","family":"Taglialegna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana E","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"2021013008052524100_dkz418-B1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/j.1365-2958.2004.04420.x","article-title":"Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates","volume":"55","author":"Pinho","year":"2005","journal-title":"Mol Microbiol"},{"key":"2021013008052524100_dkz418-B2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/thoraxjnl-2015-207983","article-title":"US Cystic Fibrosis Foundation and 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