Emerging high-level ciprofloxacin-resistant Salmonella enterica serovar Typhi haplotype H58 in travelers returning from India to the Republic of Korea

Abstract

AbstractIn Korea, typhoid fever is a rare disease due to improved living standards. However, this disease remains a major burden in developing countries and regions, such as India and Southeast Asia, In this study, we isolated Salmonella Typhi (S. Typhi) from eight typhoid patients, travelers returning from India. Isolated strains characterized with antimicrobial susceptibility profile and whole genome sequencing (WGS) analysis.All strains were resistant to nalidixic acid and azithromycin. Among them, four isolates were highly resistant to ciprofloxacin (MIC ≥32 μg/ml) and never confirmed in Korea PulseNet DB. On the basis of the WGS, we found that the ciprofloxacin-resistant strain belonged to global dominant multi-drug resistant (MDR) genotype, haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) not harbour MDR plasmid. They have H58-associated SNPs in membranes and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH. Also, Phylogenetic analysis showed that H58 strains were assigned sublineage II, and the non-H58 strains were closely related to haplotype H50.High-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as influx from overseas by travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.Author summaryTyphoid fever is a systemic human disease including gastroenteritis, fever, and severe diarrhea, caused by Salmonella enterica serotype typhi (S. Typhi), and requires prompt antibiotic treatment. Due to improved living standards, it has become a rare disease but still prevalent in developing countries such as India and Southeast Asia. Most of the reported case were related with travelers or immigrants from these regions. There is global health problem that emergence of antimicrobial resistant strain associated with fluoroquinolones and third-generation cephalosporins because of leading to treatment failure, serious morbidity, and as well as economic loss. Of antimicrobial resistant S. Typhi, haplotype H58 is a dominant multi-drug resistant lineage and has reported in endemic region over past two decades. We identified fluoroquinolones resistance in S. Typhi infected after travel to India. Among them, some strains highly resistant to ciprofloxacin were confirmed to have characteristics of haplotype H58. In Korea, S. Typhi haplotype H58 from traveller has not been confirmed before. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.