Bedaquiline and linezolid MIC distributions and epidemiological cut-off values for Mycobacterium tuberculosis in the Latin American region

Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriologia; Argentina.Fil: Siqueira de Oliveira, Rosangela. Instituto Adolfo Lutz Sao Paulo. Centro de Bacteriología. Nucleo de Tuberculose e Micobacterioses; Brasil.Fil: Pinhata, Juliana M. W. Instituto Adolfo Lutz Sao Paulo. Centro de Bacteriología. Nucleo de Tuberculose e Micobacterioses; Brasil.Fil: Chimara, Erica. Instituto Adolfo Lutz Sao Paulo. Centro de Bacteriología. Nucleo de Tuberculose e Micobacterioses; Brasil.Fil: Pacheco Ascencio, Edson. Instituto Nacional de Salud. Laboratorio de Referencia Nacional de Micobacterias; Lima, Perú.Fil: Puyén Guerra, Zully M. Instituto Nacional de Salud. Laboratorio de Referencia Nacional de Micobacterias; Lima, Perú.Fil: Wainmayer, Ingrid. ANLIS Dr.C.G.Malbrán. Insituto Nacional de Enfermededades Infecciosas. Servicio de Micobacterias; Argentina.Fil: Simboli, Norberto. ANLIS Dr.C.G.Malbrán. Insituto Nacional de Enfermededades Infecciosas. Servicio de Micobacterias; Argentina.Fil: Del Granado, Mirtha. Pan American Health Organization; Estados Unidos.Fil: Palomino, Juan Carlos. Ghent University. Department of Biochemistry and Microbiology. Faculty of sciences; Belgica.Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Insituto Nacional de Enfermededades Infecciosas. Servicio de Micobacterias; Argentina.Fil: Martín, Anandi. Université catholique de Louvain. Institute of Experimental and Clinical Research. Laboratory of Medical Microbiology; Belgica.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