Ofloxacin resistance in Mycobacterium tuberculosis: An increasing concern

Abstract

Multidrug resistance tuberculosis (MDR-TB) associated with the development of resistance to fluoroquinolones (FQs) especially ofloxacin is a matter of concern, as they had been earlier recommended drugs for usage in the MDR-TB treatment regimens, and moxifloxacin and other quinolones are still on the list. Mycobacterium tuberculosis acquires resistance to FQs mainly through mutations in the quinolone resistance determining regions (QRDRs) of the gyrA gene and less frequently in the gyrB gene. A literature search on the geographical distribution of ofloxacin resistance in TB shows that there is a mild surge in reporting of the resistance to ofloxacin in tuberculosis patients. Molecular tests demonstrating mutations in gyrA and gyrB genes is widely used to detect ofloxacin resistance and the broadly available commercial assay for the rapid detection of second-line-drug resistance, including FQ resistance, the GenoType MTBDRsl assay (Hain Life science, Nehren, Germany), detects the most common mutations found in the QRDR of gyrA while its new version 2.0 detects mutations in the gyrB as well. It has been shown that on reviewing the frequency and geographic distribution of gyrA and gyr B mutations associated with FQ resistance, there do exist geographic differences in the frequencies within and across countries. Cross-resistance to FQs is an area of concern, although some studies show that concordance in resistance among the FQ agents, lower level of cross-resistance has also been reported. The presence of ofloxacin resistance is an alarm signal while Moxifloxacin and other FQs are still the recommended drugs for the resistant TB cases. The WHO recommendation that ofloxacin be phased out from MDR-TB regimens is well justified. It is important that rationale usage of ofloxacin is needed for preventing ofloxacin resistance, to aid in the management of tuberculosis.