Mutant prevention concentration: Comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis

Abstract

Objectives: The mutant prevention concentration (MPC) has recently been defined to characterize the capacity for severely restricting the selection of resistant mutants during antibiotic treatment. We determined this parameter for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid in Mycobacterium tuberculosis clinical isolates in our setting. Methods: We determined the antibiotic concentration that prevents the selection of resistant mutants following inoculation with a high mycobacteria inoculum on Middlebrook 7H11 plates with serial dilutions of the antibiotics in 224 M. tuberculosis isolates. Results: Fifty percent of the strains exhibited values of MPC (MPC50) lower than 0.8, 0.6, 0.4, 0.4 and 0.6 mg/L for ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid, respectively. If 90% of the strains are considered (MPC90), the values are seen to rise to 2, 1.8, 1, 1.2 and 1.2 mg/L, respectively. Conclusions: When we compare this parameter with the drug levels in serum and tissue, it can be seen that ciprofloxacin is the least useful of the fluoroquinolones studied, whereas moxifloxacin appears to be the most active. Linezolid exhibits excellent activity against this microorganism (MPC90 1.2 mg/L and AUC 140.3 mg·h/L) and this makes us consider that its usefulness in the treatment of this pathology should be thoroughly evaluated. © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.