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

In Korea, typhoid fever is a rare disease due to improved living standards. However, typhoid fever 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 patients with typhoid fever who were travelers returning from India. The strains isolated were characterized by antimicrobial susceptibility profiling 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); these strains have not been confirmed in Korea PulseNet DB. According to WGS, the ciprofloxacin-resistant strains belong to the global dominant multidrug-resistant (MDR) haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) and do not harbor the MDR plasmid. H58-associated SNPs in membrane and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH, are present. Additionally, phylogenetic analysis assigned the H58 strains to sublineage II, whereas the non-H58 strains are closely related to haplotype H50. The presence of high-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as due to influx from overseas via travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.