Persistent circulation of a fluoroquinolone-resistant Salmonella enterica Typhi clone in the Indian subcontinent

Abstract

Background The molecular structure of circulating enteric fever pathogens was studied using hospital-based genomic surveillance in a tertiary care referral centre in South India as a first genomic surveillance study, to our knowledge, of blood culture-confirmed enteric fever in the region. Methods Blood culture surveillance was conducted at St John’s Medical College Hospital, Bengaluru, between July 2016 and June 2017. The bacterial isolates collected were linked to demographic variables of patients and subjected to WGS. The resulting pathogen genomic data were also globally contextualized to gauge possible phylogeographical patterns. Results Hospital-based genomic surveillance for enteric fever in Bengaluru, India, identified 101 Salmonella enterica Typhi and 14 S. Paratyphi A in a 1 year period. Ninety-six percent of isolates displayed non-susceptibility to fluoroquinolones. WGS showed the dominant pathogen was S. Typhi genotype 4.3.1.2 (H58 lineage II). A fluoroquinolone-resistant triple-mutant clone of S. Typhi 4.3.1.2 previously associated with gatifloxacin treatment failure in Nepal was implicated in 18% of enteric fever cases, indicating ongoing inter-regional circulation. Conclusions Enteric fever in South India continues to be a major public health issue and is strongly associated with antimicrobial resistance. Robust microbiological surveillance is necessary to direct appropriate treatment and preventive strategies. Of particular concern is the emergence and expansion of the highly fluoroquinolone-resistant triple-mutant S. Typhi clone and its ongoing inter- and intra-country transmission in South Asia, which highlights the need for regional coordination of intervention strategies, including vaccination and longer-term strategies such as improvements to support hygiene and sanitation.

Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India

“…The recent trends in the development of antimicrobial resistance (AMR) among S. Typhi in India proposed that multidrug resistant (MDR) enteric fever was decreasing in India and being replaced by enteric fever with fluoroquinolone resistant strains 22 . Similarly, hospital-based genomic surveillance for enteric fever in Bengaluru, India using WGS method suggested that large number of isolates showed non-susceptibility to fluoroquinolones 23 . Genome characterization assessment for AMR and pan genome of clinical isolates in endemic countries like India will assist recognition of variations in resistance mechanism and epidemiology leading to better selection of antimicrobial therapy and implementation of appropriate preventive measures.…”

Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes

“…This hospital-based surveillance took place in a tertiary care setting in Bangalore, South India, as described previously [7]. For the purpose of this study, between June 2016 and June 2017, every microbiological specimen (113 blood cultures and 1 joint aspirate) that was positive for a typhoidal Salmonella organism (confirmed by biochemical and serological means) was stored.…”

“…For the purpose of this study, between June 2016 and June 2017, every microbiological specimen (113 blood cultures and 1 joint aspirate) that was positive for a typhoidal Salmonella organism (confirmed by biochemical and serological means) was stored. The stored isolates were then sequenced, and the identity of these genomes were confirmed by multilocus sequence typing (MLST) and subsequently genotyped as described previously [7]. These were then linked to electronic patient records for relevant demographic and laboratory (complete blood counts, liver function tests and Widal serology) details after relevant ethics approvals [7].…”

“…The stored isolates were then sequenced, and the identity of these genomes were confirmed by multilocus sequence typing (MLST) and subsequently genotyped as described previously [7]. These were then linked to electronic patient records for relevant demographic and laboratory (complete blood counts, liver function tests and Widal serology) details after relevant ethics approvals [7].…”

“…The most common circulating genotype of S. Typhi in South Asia is H58 (4.3.1) [ 5 ]. Longitudinal as well as a cross-sectional data from two separate hospital-based studies in Southern India confirmed that 4.3.1 was the dominant genotype in both settings, making up 77.8% and 88.2 % of the pathogen population in the respective study sites [ 6 , 7 ].…”