Ciprofloxacin and Ceftriaxone Resistance Seen in US Typhoid Isolates

Most typhoid and paratyphoid fever isolates from US patients diagnosed from 2016 to 2020 were not susceptible to ciprofloxacin, and ceftriaxone resistance was observed among typhoid isolates, according to a cross-sectional study by CDC investigators published in JAMA Network Open.

The study assessed enteric fever resistance after an extensively drug-resistant (XDR) strain of Salmonella enterica serotype Typhi was first reported in Pakistan in 2016. Investigators linked national surveillance case reports with isolate testing from the National Antimicrobial Resistance Monitoring System (NARMS).

The study included 2342 culture-confirmed cases, 76.2% of which were typhoid. Most cases were travel associated, most often with India, Pakistan, and Bangladesh. Among 1635 linked isolates, 78.4% of Typhi and 94.2% of Paratyphi A isolates were not susceptible to ciprofloxacin. Among Typhi isolates, 5.5% were resistant to ceftriaxone, 4.9% were XDR, and 8.7% were multidrug resistant (MDR), defined as resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole and nonsusceptible to ciprofloxacin. Paratyphi isolates showed no ceftriaxone resistance or MDR or XDR patterns.

In NARMS trend data, which were preliminary for 2020 to 2023, XDR Typhi was first identified in the US in 2018, peaked at 13.5% of Typhi isolates in 2020, and accounted for 5.6% in 2023. In unadjusted analyses, travel to the Indian subcontinent was associated with higher odds of MDR and XDR Typhi infection, and travel to Pakistan with XDR infection, although the confidence intervals were very wide. Of 67 XDR cases, 11 occurred in patients who reported no international travel.

The authors said their findings suggest that ciprofloxacin should not be used empirically for most travel-associated enteric fever, that ceftriaxone should be avoided as empiric treatment for typhoid fever after travel to Pakistan and used with caution after travel elsewhere in southern Asia, and that treatment should be tailored to susceptibility results. Limitations included unlinked laboratory results for 30.2% of case records, analyses that did not account for confounders, and altered travel in 2020.

Source: Stager CH, Dorough L, Steele M, et al. Enteric fever and antimicrobial resistance. JAMA Netw Open. 2026;9(10):e2640971. doi:10.1001/jamanetworkopen.2026.40971