1. Bedaquiline and linezolid MIC distributions and epidemiological cut-off values for Mycobacterium tuberculosis in the Latin American region.
- Author
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Lopez B, Siqueira de Oliveira R, Pinhata JMW, Chimara E, Pacheco Ascencio E, Puyén Guerra ZM, Wainmayer I, Simboli N, Del Granado M, Palomino JC, Ritacco V, and Martin A
- Subjects
- Argentina, Brazil, Drug Resistance, Multiple, Bacterial, Humans, Microbial Sensitivity Tests, Oxazines pharmacology, Peru, Reference Values, Reproducibility of Results, Tuberculosis, Multidrug-Resistant epidemiology, Xanthenes pharmacology, Antitubercular Agents pharmacology, Diarylquinolines pharmacology, Linezolid pharmacology, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant microbiology
- Abstract
Objectives: To describe the distributions of bedaquiline and linezolid MIC values for the Mycobacterium tuberculosis WT population and to define the corresponding epidemiological cut-offs (ECOFFs) in three Latin American countries., Methods: MICs of bedaquiline and linezolid were determined by the resazurin microtitre assay (REMA). In phase 1, interlaboratory reproducibility was assessed using a panel of 10 fully susceptible M. tuberculosis strains. Phase 2 involved MIC determination for 248 clinical isolates from Argentina (n = 58), Brazil (n = 100) and Peru (n = 90) from patients who were treatment-naive for bedaquiline and linezolid. We then determined the ECOFFs for bedaquiline and linezolid by the eyeball method and the ECOFFinder statistical calculator., Results: Phase 1: REMA MIC values in the three sites were either identical to each other or differed by one 2-fold dilution from the consensus value with the exception of a single value. Phase 2: the bedaquiline MIC range was 0.0039-0.25 mg/L for pan-susceptible and drug-resistant isolates combined. The linezolid MIC range was 0.062-0.5 mg/L for pan-susceptible isolates and 0.031-4 mg/L for drug-resistant isolates. ECOFFs were 0.125 mg/L for bedaquiline and 0.50 mg/L for linezolid., Conclusions: REMA is reproducible and robust for the determination of bedaquiline and linezolid MIC distributions and ECOFF values when applied in laboratories of medium/low-resource countries. We suggest that WT MIC distributions for both drugs should be used as a monitoring tool to control the possible rapid emergence of resistance.
- Published
- 2019
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