igyrA/iGene Mutation Conferring Phenotypic Cross-Resistance among Fluoroquinolones (Ofloxacin, Levofloxacin and Gatifloxacin) in Multidrug Resistant iMycobacterium tuberculosis/iStrains Isolated from Pulmonary MDR-TB Patients in Bangladesh

摘要

Background and objectives: Fluoroquinolones (FLQs) are an essential component of multidrug resistant-tuberculosis (MDR-TB) treatment regimen but unfortunately the emergence of FLQ resistant MDR-TB cases is challenging the current MDR-TB treatment regimen. FLQ resistance is mainly caused by gyrA gene mutation and phenotypic cross-resistance may occur among the different FLQs. A limited number of data exists regarding the cross-resistance phenomenon among FLQs and it appears that resistance to the present class representative FLQ, ofloxacin (OFX), may or may not correlate with complete cross-resistance to other FLQs. So the study was designed to observe if gyrA gene mutations confer to the phenotypic cross-resistance among FLQs [OFX, Levofloxacin (LFX) and Gatifloxacin (GFX)] tested. Methodology: Sputum samples from 68 diagnosed pulmonary MDR-TB cases were collected. All samples were subjected to Multiplex Real-time PCR for the detection of gyrA gene mutations and conventional culture on Lowenstein-Jensen (L-J) media followed by drug sensitivity testing (DST) of culture isolates (MDR-TB strains) by indirect proportion method for the detection of phenotypic resistance pattern to OFX, LFX and GFX. Results: Out of the 68 MDR-TB sputum samples 13 (19.11%) had MDR-TB bacilli with mutations in the gyrA gene and 11(16.18%) of the MDR-TB culture isolates were found to have resistance to FLQs by DST. The study observed that 11 MDR-TB samples with gyrA gene mutations showed complete phenotypic cross-resistance among OFX, LFX and GFX. Conclusion: This study found that mutation in the gyrA gene of the MDR-TB bacilli results in the complete cross-resistance among the FLQs (OFX, LFX and GFX) tested. It is therefore of utmost importance to carry out the base line resistance and cross-resistance tests for the individual FLQs prior to initiating the treatment of MDR-TB cases in Bangladesh for successful clinical outcomes.