title: In vitro time-kill curves study of three antituberculous combinations against Mycobacterium tuberculosis clinical isolates.
abstract: The objective of this study was to examine the in vitro synergism of three-drug combinations against Mycobacterium tuberculosis (levofloxacin/linezolid/ethambutol, levofloxacin/amikacin/ethambutol and levofloxacin/linezolid/amikacin) using the time-kill curves method. In total, 8 multidrug-resistant and 12 drug-susceptible M. tuberculosis isolates were used. Minimum inhibitory concentrations (MICs) of the isolates for each drug were determined by the proportions method. Time-kill curves were studied for the three combinations proposed over 14 days using two different protocols. In protocol 1, 0.5× MIC for each drug was used. In protocol 2, 0.5× MIC for levofloxacin and linezolid and 0.25× MIC for amikacin and ethambutol were used. The MICs for all of the isolates studied were 0.5 mg/L for levofloxacin and linezolid and 2.5 mg/L for ethambutol and amikacin. All of the combinations displayed an additive activity compared with the most active individual drug. In conclusion, these results demonstrate that the three combinations tested were equally effective against M. tuberculosis isolates. The study of antituberculous combinations using in vitro methods is an excellent first step to predict their effect in clinical development phases as well as to test new regimens of the antituberculous drugs currently available.
authors.affiliation: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-ISGlobal, Universitat de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: López-Gavín
authors.affiliation: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-ISGlobal, Universitat de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Griselda
authors.initials: G
authors.lastname: Tudó
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Emma
authors.initials: E
authors.lastname: Rey-Jurado
authors.affiliation: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-ISGlobal, Universitat de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vergara
authors.affiliation: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-ISGlobal, Universitat de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hurtado
authors.affiliation: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-ISGlobal, Universitat de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain. Electronic address: gonzalez@clinic.ub.es.
authors.forename: Julian
authors.initials: J
authors.lastname: Gonzalez-Martín
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations
keywords: Antituberculous drugs; Combinations; Time–kill; Tuberculosis