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Lefamulin (formally <jats:styled-content style=\"fixed-case\">BC<\/jats:styled-content>\u20103781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community\u2010acquired bacterial pneumonia (<jats:styled-content style=\"fixed-case\">CABP<\/jats:styled-content>) as intravenous (<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>) and oral (<jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans. Lefamulin exhibits a unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA for peptide transfer. Lefamulin displays activity against gram\u2010positive and atypical organisms associated with <jats:styled-content style=\"fixed-case\">CABP<\/jats:styled-content> (i.e., <jats:italic>Streptococcus pneumoniae<\/jats:italic>,<jats:italic> Haemophilus influenzae, Mycoplasma pneumoniae<\/jats:italic>,<jats:italic> Legionella pneumophila<\/jats:italic>, and <jats:italic>Chlamydophila pneumoniae<\/jats:italic>), with an expanded gram\u2010positive spectrum including <jats:italic>Staphylococcus aureus<\/jats:italic> (i.e., methicillin\u2010resistant, vancomycin\u2010intermediate, and heterogeneous strains) and vancomycin\u2010resistant <jats:italic>Enterococcus faecium<\/jats:italic>. Lefamulin was also shown to retain activity against multidrug\u2010resistant <jats:italic>Neisseria gonorrhoeae<\/jats:italic> and <jats:italic>Mycoplasma genitalium<\/jats:italic>. Lefamulin exhibits time\u2010dependent killing, and the pharmacodynamic target best associated with antibacterial activity is <jats:styled-content style=\"fixed-case\">\u0192AUC<\/jats:styled-content><jats:sub>0\u201324<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content> (minimum inhibitory concentration [MIC]). Preclinical and phase II trials indicate that lefamulin concentrates in lung tissue are well tolerated at an <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> dose of 150\u00a0mg twice\/day over 1\u00a0hour or a <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> dose of 600\u00a0mg twice\/day, and preliminary phase III data suggest similar efficacy when compared with moxifloxacin with or without linezolid in <jats:styled-content style=\"fixed-case\">CABP<\/jats:styled-content>. Documented resistance and cross\u2010resistance with other gram\u2010positive antibacterials remains low. Additional published in\u00a0vitro, in\u00a0vivo, and preclinical trial data suggest further exploration of lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for lefamulin.<\/jats:p>","DOI":"10.1002\/phar.2166","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T01:31:40Z","timestamp":1531963900000},"page":"935-946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5967-5211","authenticated-orcid":false,"given":"Michael P.","family":"Veve","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science University of Tennessee Health Science Center Knoxville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6006-7894","authenticated-orcid":false,"given":"Jamie L.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice University of Mississippi Jackson Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1894OE"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2005\/892058"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/652237"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.09.025"},{"key":"e_1_2_11_6_1","unstructured":"Antibiotics currently in global clinical development. 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