In vitro activity against Mycobacterium tuberculosis of levofloxacin, moxifloxacin and UB-8902 in combination with clofazimine and pretomanid

• All the combinations studied are equally effective against M. tuberculosis isolates.
• The combinations studied have additive effect against M. tuberculosis isolates.
• Time kill studies are adequate to optimize chemotherapy based on combinations.

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.