Risk assessment and transmission of fluoroquinolone resistance in drug-resistant pulmonary tuberculosis in South India: a retrospective genomic epidemiology study

Abstract

Fluoroquinolone resistance is a significant global challenge in treating multidrug-resistant tuberculosis. The WHO-endorsed GenoType MTBDRsl Ver 2.0 was used for a retrospective analysis of the molecular characterization of fluoroquinolone resistance. The FQ resistance rates in MDR-TB, RR-TB, and non-MDR-TB cases were 33%, 16.5%, and 5.4%, respectively. The most common mutation in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. In MDR-TB isolates, the prevalence of XDR-TB and pre-XDR-TB was 1.33% and 30% respectively. Among the 139 rifampicin-monoresistant tuberculosis isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rate was 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB has a significantly higher risk (RR = 4.03; 95%CI: 2.94-5.53) of having fluoroquinolone resistance compared to non-MDR (RR = 0.26; 95%CI: 0.19-0.35) and rifampicin-monoresistant tuberculosis (RR=1.85; 95%CI: 1.22-2.80). Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 3.97; 95%CI: 2.90-5.44) for fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the transmission and amplification of resistance and achieve better treatment outcomes, especially in South India, where fluoroquinolone resistance is higher.