Whole-genome sequencing for surveillance of fluoroquinolone resistance in rifampicin-susceptible tuberculosis in a rural district of Shanghai: A 10-year retrospective study

Abstract

BackgroundFluoroquinolones (FQs) are the most important second-line anti-tuberculosis (anti-TB) drugs, primarily used for the treatment of multidrug- or rifampicin-resistant TB (MDR/RR-TB). However, FQs are also commonly used to treat other bacterial infections. There are few published data on the rates of FQ resistance among rifampicin-susceptible TB.MethodsWe used whole-genome sequencing (WGS) to determine the prevalence of FQ resistance among rifampicin-susceptible TB in a rural district of Shanghai. This was a population-based retrospective study of all culture-positive pulmonary TB patients diagnosed in the Chongming district of Shanghai, China during 2009–2018.ResultsThe rate of FQ resistance was 8.4% (29/345) among TB, 6.2% (20/324) among rifampicin-susceptible TB, and 42.9% (9/21) among MDR/RR-TB. Transmission of FQ-resistant strains was defined as strains differing within 12 single-nucleotide polymorphisms (SNPs) based on WGS. Among the rifampicin-susceptible TB, 20% (4/20) of FQ resistance was caused by the transmission of FQ-resistant strains and 45% (9/20) of FQ resistance was identified as hetero-resistance.ConclusionsThe prevalence of FQ resistance in rifampicin-susceptible TB was higher than expected in Shanghai. Both the transmission and the selection of drug-resistant strains drive the emergence of FQ resistance in rifampicin-susceptible TB isolates. Therefore, the WGS-based surveillance system for TB should be urgently established and the clinical awareness of the rational use of FQs for respiratory infections should be enhanced to prevent the premature occurrence of FQ resistance.

Mutations in the promoter region of methionine transporter gene metM (Rv3253c) confer para -aminosalicylic acid (PAS) resistance in Mycobacterium tuberculosis

“…Clinical trials have been conducted to identify the most appropriate PAS-containing regimens for patients with MDR-TB or XDR-TB ( 15 , 16 ). In the current clinical research, WGS is increasingly employed in lieu of traditional susceptibility methods to diagnose second-line drug resistance in TB ( 17 – 19 ). However, PAS resistance based solely on WGS is challenging, as some PAS resistance mechanisms remain unidentified.…”

Transmission of fluoroquinolones resistance among multidrug-resistant tuberculosis in Shanghai, China: a retrospective population-based genomic epidemiology study

“…Therefore, we cannot disregard the possibility that residents are more likely to be exposed to FQ during medical treatment. Besides, previous studies have shown that FQ is a commonly used antibiotic drug in hospitals or pharmacies in Shanghai [ 32 ], and even the FQ-R rate in RIF-susceptible TB is as high as 6% in the rural district of Shanghai [ 33 ]. Overall, easy access and inappropriate use of FQ can increase drug resistance risk, highlighting the importance of regulated use and strict management of FQ in China’s local medical institutions.…”

Culture-free whole genome sequencing ofMycobacterium tuberculosisusing ligand-mediated bead enrichment method

“…India contributes to the world's highest TB incidence, with approximately 3 million cases annually (2). Over the last decade, due to the accessibility of low-cost benchtop sequencers, streamlined workflows, and a faster turnaround time, whole genome sequencing has rapidly evolved from a mere research tool to a clinical platform with the ability to identify the pathogen and its resistance to drugs (3), investigate transmission (4), and conduct public health surveillance (5)(6)(7). However, whole-genome sequencing has not yet entered the mainstream of clinical diagnosis in tuberculosis, mainly due to the requirement of culturing Mtb prior to sequencing.…”