Enteric Fever and Antimicrobial Resistance

Importance: Increasing antibiotic resistance in enteric fever (typhoid or paratyphoid fever) is a global public health threat. Knowledge of current antimicrobial resistance patterns and identification of factors associated with acquiring resistant infections can help inform treatment and prevention decisions. Objective: To estimate the prevalence of antimicrobial-resistant enteric fever in the US after the emergence of extensively drug-resistant Salmonella enterica Typhi in 2016 and describe characteristics of patients with resistant Salmonella Typhi or Paratyphi strains. Design, Setting, and Participants: This cross-sectional, laboratory-based study included cases of culture-confirmed enteric fever diagnosed in the US. From January 2016 to December 2020, US health departments submitted epidemiologic data to the Centers for Disease Control and Prevention (CDC) through the National Typhoid and Paratyphoid Fever Surveillance (NTPFS) system, and public health laboratories submitted the corresponding Typhi or Paratyphi isolates to the CDC through the National Antimicrobial Resistance Monitoring System (NARMS). Initial data analysis was complete by March 31, 2023, and the antimicrobial resistance trends analysis was updated in August 2026. Exposures: Patient variables collected by the NTPFS, including demographic characteristics, travel history, and typhoid vaccination status. Main Outcome and Measures: Linked NTPFS-NARMS data from 2016 to 2020 were used to calculate the prevalence of antimicrobial resistance stratified by serotype and to conduct univariable logistic regression to estimate the associations of case characteristics and exposure variables with odds of infection with resistant strains. Results: In this analysis, 2342 cases were included (1784 typhoid [76.2%], 426 paratyphoid A [18.2%], 114 paratyphoid B [4.9%], and 14 paratyphoid C [0.6%]; 4 isolates [0.2%] had unspecified paratyphoid serotypes). The median patient age was 25 years (IQR, 11-37 years), and patients were male in 1215 of 2325 cases (52.3%). Most patients reported traveling or residing internationally within 30 days of illness onset (1853 of 2217 [81.9%]). From 2016 to 2020, 1635 enteric fever isolates underwent susceptibility testing through NARMS; most Typhi (1061 of 1354 [78.4%]) and Paratyphi A (258 of 274 [94.2%]) isolates were not susceptible to ciprofloxacin. Among 1354 Typhi isolates, resistance exceeded 15% for ampicillin, for chloramphenicol, and for trimethoprim-sulfamethoxazole and was 5.5% (74 isolates) for ceftriaxone; 1 Typhi isolate (0.1%) was resistant to azithromycin. Resistance to these agents was not observed among Paratyphi isolates. Conclusions and Relevance: In this cross-sectional study, most typhoid and paratyphoid infections were not susceptible to ciprofloxacin, suggesting that ciprofloxacin should be avoided as empiric therapy for most travel-associated enteric fever cases. Cases of ceftriaxone-resistant typhoid fever were also observed. These findings suggest that treatment of enteric fever should be tailored to susceptibility test results.