RT Journal Article
SR Electronic
T1 23S rRNA mutations in linezolid-resistant clinical isolates of M. tuberculosis: A report of two cases
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4428
VO 42
IS Suppl 57
A1 Myungsun Lee
A1 Taeksun Song
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P4428.abstract
AB Use of linezolid for the treatment of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis is increasing. We have recently showed linezolid is effective at achieving culture conversion among patients with treatment refractory XDR pulmonary tuberculosis in our randomized controlled trial.Exposure to the drug, however, eventually resulted in the selection of resistant organism, and understanding of the mechanism of acquired resistance is important in clinical decision making during treatment. In two cases who failed treatment mutations in 23S rRNA were identified in linezolid-resistant strains isolated from the patients.Case 1: A 30-year-old female had started linezolid with background regimen(BR) for pulmonary tuberculosis. Sputum was not converted negative after 6 months of treatment and the case was regarded as a failure. MIC of the isolate at week 26 indicated the development of resistance, 32-fold increase. Sequencing of the isolate revealed the acquisition of a mutation in 23S rRNA, G2447U.Case 2: A 46-year-old male had started linezolid with BR for the treatment of pulmonary tuberculosis. His sputum culture had converted negative after 14 weeks of treatment. At week 45 sputum reverted positive followed by consecutive positivity, which indicated treatment failure. The isolate at week 45 showed an increase in MIC (8 folds) and another mutation in 23S rRNA, G2576U, was identified. Backward analysis of the isolates revealed the advent of the same mutation at week 13 already.Examination for the resistance-conferring mutations could be useful to anticipate treatment outcome.