Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5667112 | International Journal of Antimicrobial Agents | 2017 | 6 Pages |
â¢SQ109 as single drug showed strong bactericidal activity against Mycobacterium tuberculosis.â¢Verapamil, timcodar and SQ109 showed no added value to the moxifloxacinâ+âlinezolid combination.â¢Colistin potentiated the moxifloxacinâ+âlinezolid combination.
Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacinâ+âlinezolid backbone as treatment for MDR-TB with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacinâ+âlinezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125âmg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256âmg/L and in 99% elimination after 6 days of exposure to 1âmg/L. Furthermore, colistin added to the moxifloxacinâ+âlinezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacinâ+âlinezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacinâ+âlinezolid treatment of MDR-TB.