Evaluation of genetic correlation with fluoroquinolones resistance in rifampicin-resistant Mycobacterium tuberculosis isolates

Evaluation of genetic correlation with fluoroquinolones resistance in rifampicin-resistant Mycobacterium tuberculosis isolates

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Objective: To detect levofloxacin (LFX) and moxifloxacin (MFX) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates, and predict the resistance level based on specific mutations in Enzyme Formula gyrA and gyrB genes.Methods: A total of 686 RR-TB isolates were collected from Chinese Drug Resistance Surveillance Program from 2013 to 2020.The minimum inhibitory concentrations (MICs) of 12 anti-TB drugs were acquired using the broth microdilution method, followed by whole genome sequencing (WGS) analysis.Results: Among the 686 RR isolates, the most prevalent resistance was to isoniazid (80.5 %) and ethambutol (28.

4 %), followed by LFX (26.1 %) and MFX (21.9 %).The resistance rate of LFX (26.1%–99.

4 %) was higher than that of MFX (21.9%–83.3 %) across various drug resistance patterns.Of the 180 fluoroquinolones (FQs) resistant isolates, 168 (93.3 %) had mutations in quinolone-resistant determining regions (QRDRs) with 21 mutation types, and Asp94Gly (32.

7 %, 55/168) was the predominant mutation.Isolates with mutations in Asp94Asn and Asp94Gly were TEA TREE PURE-CASTILE SOAP associated with high levels of resistance to LFX and MFX.Using broth microdilution method as gold standard, the sensitivities of WGS for LFX and MFX were 93.3 % and 98.0 %, and the specificities were 98.

6 % and 95.0 %, respectively.Conclusion: The resistance rate of LFX was higher than that of MFX among various drug resistance patterns in RR-TB isolates.The gyrA Asp94Gly was the predominant mutation type underlying FQs resistance.However, no significant difference was observed between mutation patterns in gyrA gene and resistance level of FQs.