Effect of Linezolid in Combination With Isoniazid and Rifampicin Against Multidrug Resistant Mycobacterium Tuberculosis Clinical Isolates

Abstract

Tuberculosis continues to be a serious public health problem worldwide. Since multi-drug resistant strains of Mycobacterium tuberculosis constitutes a serious problem in tuberculosis control, new and more effective chemotherapeutic agents are required. This study was aimed to investigate the in vitro effect of linezolid alone and in combination with isoniazid and rifampicin against 10 multidrug resistant M.tuberculosis isolates by using the checkerboard method. Checkerboard testing was performed by the broth microdilution method, using Middlebrook 7H9 broth with 10% oleic acid-albumin-dextrose-catalase. Antibiotic combinations were tested at concentrations of 0.06-4 mu g/ml for linezolid and 0.03-32 mg/ml for isoniazid and rifampicin. The results were evaluated according to the calculated fractional inhibitory concentration (FIC) index. All clinical isolates were found to be susceptible to linezolid; MICs of linezolid were 0.25 mu g/ml for two strains and 0.5 mu g/ml for the other strains. While rifampicin MIC values were > 32 mu g/ml for all the isolates, isoniazid MIC values were 4 mu g/ml for two isolates, 8 mu g/ml for six isolates, 16 mu g/ml for one isolate and 32 mu g/ml for one isolate. In this study, synergism was detected in only one strain between linezolid and isoniazid (FIC index: 0.265). Although synergy was observed between linezolid and isoniazid just for one strain, further larger scale in vitro and in vivo studies are necessary to evaluate the effect of different drug combinations against multidrug-resistant M.tuberculosis strains.