Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern China

Abstract

Empirical use of fluoroquinolones (FQ) to treat a variety of bacterial infections may inadvertently select for FQ-resistant strains of Mycobacterium tuberculosis(MTB), especially in rural China where the use of FQ in treating infections has not been standardized. Here we determine the prevalence and describe the transmission of FQ-resistant MTB in two rural counties in eastern China through a combination of conventional epidemiology with IS6110-based restriction fragment length polymorphism(RFLP) analysis and DNA sequencing of drug-resistance determining regions. Phenotypic FQ resistance was detected in 31 of 351(8.8%) isolates. FQ resistance was equally distributed between patient-isolates deemed drug resistant and drug-susceptible, but mostly observed in those with treatment history of respiratory infection. Mutations in gyrA were found in 54.8% of FQ resistant isolates, and one isolate with a gyrB mutation. Despite predominating in entire bacilli population(69.2%), Beijing family strain had similar proportion of FQ resistance to the other(10.3% vs. 4.7%, p = 0.060). IS6110RFLP identified 2 clusters(4 isolates) among FQ resistant isolates and 3 clusters composed of both 4 FQ resistant isolates and 6 FQ susceptible isolates. Our results indicate that FQ-resistant MTB has emerged among the circulating bacillary population in rural eastern China. The relatively low level of clustering among FQ-resistant strains suggests most are acquired de novo, likely due to widespread FQ use.