Abstract
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.
Highlights
Fluoroquinolones (FLQs) are broad spectrum antibiotics which have been successfully used in the treatment of Tuberculosis (TB) since 1984 and have become an essential component of multidrug resistant-tuberculosis (MDR-TB) treatment regimen [1]
FLQ resistance is mainly caused by gyrA gene mutation and phenotypic cross-resistance may occur among the different FLQs
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
Summary
Fluoroquinolones (FLQs) are broad spectrum antibiotics which have been successfully used in the treatment of Tuberculosis (TB) since 1984 and have become an essential component of MDR-TB (multidrug resistant-tuberculosis) treatment regimen [1]. When a Mycobacterium tuberculosis strain isolated from a patient exhibits resistance to rifampicin (RIF) and isoniazid (INH), it is termed MDR-TB and the patients infected with MDR-TB strains are called MDR-TB patients. Such MDR-TB patients are initiated on a FLQ containing treatment regimen that is very effective [2]. 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
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