title: In vitro activity against Mycobacterium tuberculosis of levofloxacin, moxifloxacin and UB-8902 in combination with clofazimine and pretomanid.
abstract: Multidrug resistance has become a problem in the management of tuberculosis, with an urgent need for research into new drugs as well as the development of efficacious drug combinations and regimens. The main objective of this study was to assess and compare the efficacy of three antituberculous combinations (clofazimine/pretomanid/levofloxacin, clofazimine/pretomanid/moxifloxacin and clofazimine/pretomanid/UB-8902) against multidrug-resistant (MDR) and drug-susceptible clinical isolates of Mycobacterium tuberculosis using an in vitro adaptation of the chequerboard assay. A total of 7 MDR and 11 drug-susceptible clinical isolates were studied. The fractional inhibitory concentration index (FICI) was interpreted as synergism when the value was <0.75, antagonism when it was >4 and additive activity between these two values. The FICI of all of the combinations ranged from 1.2 to 2.3, showing additive activity against all of the isolates. No differences were found between MDR and drug-susceptible isolates. In conclusion, the three combinations are effective against M. tuberculosis with equal effects. Moreover, in vitro testing of drug combinations could be useful to predict their clinical use.
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: 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*; D002991:Clofazimine / Q000494:pharmacology*; D004347:Drug Interactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D009593:Nitroimidazoles / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D009593:Nitroimidazoles; D002991:Clofazimine
keywords: Chequerboard assay; Mycobacterium tuberculosis; Synergy