Molecular Characteristic of Both Levofloxacin and Moxifloxacin Resistance in Mycobacterium tuberculosis from Individuals Diagnosed with Preextensive Drug-Resistant Tuberculosis.

Abstract

Aim: Fluoroquinolones (FQs) are the cornerstone in treating drug-resistant tuberculosis (TB); the prevalence of TB among the population is diverse in different regions, understanding the relationship between resistance pattern and molecular characteristic of FQs in preextensive drug-resistant (pre-XDR) clinical isolates is limited in China. Methods: A total of 141 pre-XDR clinical isolates from different individuals stored at the National Clinical Centre were collected from the Beijing Chest Hospital, minimal inhibitory concentrations of levofloxacin (Lfx) and moxifloxacin (Mfx) as well as sequences of quinolone-resistant determining regions in gyrA and gyrB genes were examined. Results: One hundred twelve pre-XDR clinical isolates were resistant to both Lfx and Mfx, molecular analyses showed that 87.50%, 0.89%, and 6.25% of the pre-XDR clinical isolates harbored FQ resistance mutations in gyrA, gyrB, and in both. We found five amino acid mutation positions in gyrA and four in gyrB, The mutation position in gyrA included codons 94, 91, 90, 88, and 74, and in gyrB included codons 504, 500, 512, and 501. Codon 94 of gyrA was the most prevalent mutation (83.04%), containing the Asp amino acid substitution with Gly (50.89%), Asn (15.17%), Ala (8.93%), Tyr (6.25%), and His (1.79%). Conclusions: The mutations of gyrA were most common and the frequency of Asp94Gly was the highest in pre-XDR clinical isolates in Beijing, China. The mutations at codon 94 significantly contributed to the resistance to both Lfx and Mfx in pre-XDR clinical isolates and may cause a high resistance level.