title: In vitro effect of three-drug combinations of antituberculous agents against multidrug-resistant Mycobacterium tuberculosis isolates.
abstract: Multidrug resistance has become a problem in the management of tuberculosis, leading to an urgent need for research related to new regimens including the currently available drugs. The objectives of this study were: (i) to study the effect of the following second-choice three-drug combinations against multidrug-resistant (MDR) and drug-susceptible clinical isolates (levofloxacin, linezolid and ethambutol; levofloxacin, amikacin and ethambutol; and levofloxacin, linezolid and amikacin); and (ii) to compare the effect of these combinations with an isoniazid, rifampicin and ethambutol combination against drug-susceptible clinical isolates. A total of 9 MDR clinical and 12 drug-susceptible isolates (11 clinical isolates and the H37Rv reference strain) were studied using an adaptation of the chequerboard assay. The fractional inhibitory concentration index (FICI) was calculated as follows: FICI=FIC(A)+FIC(B)+FIC(C)=A/MIC(A)+B/MIC(B)+C/MIC(C), where A, B and C are the minimum inhibitory concentrations (MICs) of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) are the individual MICs. The FICI was interpreted as synergism when the value was <0.75. The FICI of all the combinations ranged from 1.5 to 3, showing indifferent activity. No differences were found between MDR and drug-susceptible isolates, or between the second-choice combinations and the fourth combination against drug-susceptible isolates. In conclusion, the second-choice drugs are equally effective as the combination of isoniazid, rifampicin and ethambutol.
authors: Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-Barcelona Centre for International Health Research-CRESIB, Dpt. Anatomia Patològica, Farmacologia i Microbiologia, Universitat de Barcelona-UB, Barcelona, Spain.
authors: Emma
authors: E
authors: Rey-Jurado
authors: Griselda
authors: G
authors: Tudó
authors: Jorge Puig
authors: JP
authors: de la Bellacasa
authors: Mateu
authors: M
authors: Espasa
authors: Julian
authors: J
authors: González-Martín
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations