Clinical Microbiology and Antimicrobial Chemotherapy. 2013; 15(1):56-65
Objectives. To study incidence and changes of fluoroquinolone resistance among Mycobacterium tuberculosis in Novosibirsk region, and to determine fluoroquinolone contribution to drug resistance selection in M. tuberculosis population.
A total of 344 clinical isolates of M. tuberculosis obtained from patients with newly diagnosed tuberculosis during the periods of 2000–2002 and 2006–2010 were tested for susceptibility to fluoroquinolones. This study included 141 isolates susceptible to first-line drugs and 83 isolates resistant to isoniazid and rifampicin (multi-drug resistance [MDR]), and 120 isolates resistant to one or more anti-TB drugs, but without MDR. Minimal inhibitory concentrations (MICs) for ofloxacin were determined using broth dilution method. Isolates demonstrating phenotypic resistance were tested for gyrA gene mutations.
Increased MICs of ofloxacin (16–32 mg/L) were observed only in MDR isolates and isolates obtained during the 2006–2010; proportion of fluoroquinoloneresistant isolates were 7.2% (95% CI: 3.4%, 14.9%) and 3.4% (95% CI: 1.5%, 7.1%), respectively. All 6 isolates showing phenotypic resistance to ofloxacin (MIC >4.0 mg/L) had mutations in QRDR region of gyrA gene conferring fluoroquinolone resistance. Proportion of M. tuberculosis strains showing primary fluoroquinolone resistance in Novosibirsk region was 6.4% (95% CI 2.9%, 13.2%).
Results from this study suggest that emergence of fluoroquinolones resistance in M. tuberculosis population is due to the use of fluoroquinolones in the treatment of tuberculosis caused by MDR strains, rather than their use in the treatment of non-mycobacterial infections, which is a threat to long-term clinical efficacy of this antimicrobial class.