<i>gyrA</i> Gene Mutation Conferring Phenotypic Cross-Resistance among Fluoroquinolones (Ofloxacin, Levofloxacin and Gatifloxacin) in Multidrug Resistant <i>Mycobacterium tuberculosis</i> Strains Isolated from Pulmonary MDR-TB Patients in Bangladesh

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%

Pre-extensively drug-resistant tuberculosis among multidrug-resistant tuberculosis patients in Ethiopia: a laboratory-based surveillance study

“…The percentage of pre-XDR-TB among MDR-TB isolates was slightly lower than reported in a previous study in Bangladesh ( Tasnim et al., 2018 ). Drug-resistance patterns in MDR-TB isolates may differ due to mutational variability in mycobacterial genes linked with anti-TB drug resistance ( Lan et al., 2019 ).…”

“…Our results showed a 3% prevalence of pre-XDR-TB. Compared with our findings, pre-XDR-TB has been found to be more common in India (56%), China (34%), Bangladesh (16%), Pakistan (24%), South Africa (17%), and Nigeria (17%), according to many studies ( Adwani et al., 2016 ; Daniel et al., 2013 ; Mlambo et al., 2008 ; Tasnim et al., 2018 ; Yuan et al., 2012 ). Additionally, a study from India showed higher prevalences of pre-XDR-TB (49.4%) and XDR-TB (11.4%) than our findings ( Singhal et al., 2016 ).…”

“…According to data from previous studies, the prevalence of FQ-resistant MDR-TB (pre-XDR-TB) has increased ( Singhal et al., 2016 ). In Ethiopia, fluoroquinolones are used indiscriminately in most common infections, including pneumonia and pyrexia of unknown origin, in addition to MTB infection, which may explain the higher prevalence of FQ-resistant pre-XDR-TB cases observed in our study ( Tasnim et al., 2018 ; Shibabaw et al., 2020 ). FQs present two disadvantages when used as antibiotics: first, their anti-mycobacterial action can delay the diagnosis of TB; second, when used for previous infections, they can lead to the selection of FQ-resistant MTB mutants ( Tasnim et al., 2018 ).…”

“…In Ethiopia, fluoroquinolones are used indiscriminately in most common infections, including pneumonia and pyrexia of unknown origin, in addition to MTB infection, which may explain the higher prevalence of FQ-resistant pre-XDR-TB cases observed in our study ( Tasnim et al., 2018 ; Shibabaw et al., 2020 ). FQs present two disadvantages when used as antibiotics: first, their anti-mycobacterial action can delay the diagnosis of TB; second, when used for previous infections, they can lead to the selection of FQ-resistant MTB mutants ( Tasnim et al., 2018 ). Since FQ antibiotics are oral medications and easily accessed in Ethiopian pharmacies without a prescription, FQ exposure is more frequent than injectable SLD exposure ( Shibabaw et al., 2020 ).…”

Association of Single Nucleotide Polymorphism rs17580 with Smoking and Pulmonary Tuberculosis

“…The base T mutation to A in rs17580, which is located in the coding region of the SERPINA1 gene, causes a change in amino acid from glutamate to valine, which alters the entire protein structure and affects the function of the encoding enzyme [ 10 , 11 ]. Studies have found that the occurrence of drug resistance of Mycobacterium tuberculosis is related to mutations of multiple genes [ 12 , 13 ]. A recent study found a high correlation between mutations in the SERPINA1 gene and chronic obstructive pulmonary disease [ 14 ].…”