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We aimed to describe mutations and clinical factors associated with phenotypic linezolid resistance from patients with drug-resistant TB at two public sector facilities in South Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adults and adolescents with treatment failure (culture positivity \u22654\u2009months) on a linezolid-containing regimen were retrospectively identified. Phenotypic resistance, as defined by a linezolid MIC &gt;1\u2009mg\/L, was assessed for retrieved isolates using broth microdilution. Targeted sequencing of rrl and rplC was performed, irrespective of growth on subculture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-nine patients with linezolid-based treatment failure were identified, 13 (33%) of whom had phenotypic or genotypic linezolid resistance after a median duration of 22\u2009months (range\u205f=\u205f7\u201332) of linezolid therapy. Paired MIC testing and genotyping was performed on 55 unique isolates. All isolates with phenotypic resistance (n\u205f=\u205f16) were associated with known resistance mutations, most frequently due to the T460C substitution in rplC (n\u205f=\u205f10); rrl mutations included G2814T, G2270C\/T and A2810C. No mutations were detected in isolates with MICs at or below the critical concentration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Linezolid resistance occurred in a third of patients with drug-resistant TB and treatment failure. Resistance occurred late and was predicted by a limited number of mutations in rrl and rplC. Screening for genotypic resistance should be considered for patients with a positive culture after 4\u2009months of linezolid therapy in order to optimize treatment and avoid the toxicity of ineffective linezolid therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz206","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T15:13:07Z","timestamp":1555427587000},"page":"2377-2384","source":"Crossref","is-referenced-by-count":56,"title":["Linezolid resistance in patients with drug-resistant TB and treatment failure in South Africa"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3508-6719","authenticated-orcid":false,"given":"Sean","family":"Wasserman","sequence":"first","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Division of Infectious 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