Introduction of Fluroquinolone-Resistant Salmonella enterica serovar Typhi Strains into Cambodia: A Phylogenomic Analysis

<jats:p>Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) is a Gram-negative bacterium responsible for typhoid fever, a significant public health concern in low- and middle-income countries, where it primarily affects children and young adults. Effective treatment relies on antimicrobial therapy; however, the emergence of antimicrobial resistance, particularly to fluoroquinolones like ciprofloxacin, has complicated management strategies. This study focuses on two ciprofloxacin-resistant S. Typhi strains isolated in January 2017 from two Indian nationals in Phnom Penh, Cambodia, marking the first documented cases of ciprofloxacin-resistant S. Typhi in the country. Through whole-genome sequencing, we aimed to determine whether these strains represented a newly imported clone or a reemergence of an endemic strain with increased resistance. Phenotypic antimicrobial susceptibility testing confirmed that both isolates were resistant to ciprofloxacin while susceptible to other tested antibiotics, including azithromycin and ceftriaxone, the current first-line treatments in regions with high ciprofloxacin resistance. Genomic analysis revealed that both strains harbored three resistance-conferring mutations gyrA-S83F, gyrA_D87N, and parC_S80I. Phylogenomic comparison of these strains with global S. Typhi datasets identified them as part of the genotype 4.3.1.2.1, a recently designated sub-lineage associated with fluoroquinolone resistance. The strains clustered closely with S. Typhi isolates from India, suggesting that they were likely imported from India rather than representing local evolution. This study reveals the likely introduction of the ciprofloxacin-resistant genotype 4.3.1.2.1 into Cambodia and underscores the importance of targeted genomic surveillance in tracking the spread of antimicrobial resistance in S. Typhi. Although the introduction of ciprofloxacin-resistant strains probably poses minimal additional threat in Cambodia, where fluoroquinolone non-susceptibility is already widespread, the potential for the spread of more resistant variants, such as those carrying ceftriaxone resistance, underscores the need for robust surveillance and the eventual adoption of typhoid vaccines in endemic regions. The study also illustrates the growing potential for LMICs to integrate whole genome sequencing into their antimicrobial resistance surveillance programs as the technology becomes more accessible, thereby enhancing public health responses to typhoid fever.</jats:p>