CDC Investigators of Enteric Fever Favor Tailored Treatment

Enteric fever (typhoid or paratyphoid fever) in the US, principally linked to returning travelers, is typically resistant to ciprofloxacin, and with some cases also resistant to "1st-choice" antimicrobials such as ceftriaxone, CDC investigators advise treating to susceptibility whenever possible.

Christan Stager, DVM, Epidemic Intelligence Service, Centers for Disease Control and Prevention (CDC), Atlanta, GA, and colleagues conducted a cross-sectional study of antimicrobial analysis of enteric fever in the US to update CDC data that had been published before the emergence of extensively drug-resistant (XDR) Typhi strain.¹ The strain, originally identified among US travelers returning from Pakistan in 2016, has subsequently been reported worldwide.

"Because resistance can evolve quickly, surveillance is important to detect emerging resistance, track trends, and guide clinical and public health decision-making," the investigators indicate.

Stager and colleagues estimate that typhoid fever, transmitted through fecal-oral route usually by contaminated water or food, affects 5,700 persons in the US annually. They note that mortality rate was over 10% in the era before effective antibiotics, and that current guidelines for effective antibiotic treatment have had to evolve with increasing nonsusceptibility reports, especially from South Asia.

"Effective treatment is complicated by increasing antimicrobial resistance to commonly prescribed antibiotics," they warn."Therefore, prevention is paramount, especially in regions with antimicrobial resistance."

Among the trends in antimicrobial resistance, the investigators found a steady increase in the proportion of Typhi isolates that were fluorquinolone nonsusceptible (FQ-NS), from 20 of 167 (12.0%) in 1999 to 373 of 497 (75.1%) in 2023. The proportion of FQ-NS Paratyphi isolates increased from 1999 to 2007, remaining at a high of between 78.9% to 96.0% after 2007.

In the period of 2016-2020, 8.7% of Typhi isolates were multidrug resistant (MDR), defined as resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. The investigators found the odds of having an MDR vs an FQ-S Typhi were higher (odds ratio [OR] 37.84, 95% CI, 19.08-80.43), and substantially higher for an XDR stain (OR 294.04, 60.41-5,314.27) among patients returning from the Indian subcontinent (Bangladesh, Bhutan,, India, Maldives, Nepal, Pakistan or Sri Lanka) compared to other destinations; with particularly high risk associated with Pakistan. The odds of resistant paratyphoid fever were also higher (OR, 21.70 [6.52-79.45]) among patients (with paratyphoid A) returning from the Indian subcontinent.

Interestingly, the investigators found that traveling for immigration had lower odds of infection with FQ-NS, MDR, or XDR strains than those who traveled to visit friends or family. "Travelers visiting friends or relatives may be less likely than other travelers to seek pre-ravel advise or attend a pre-travel health care consultation, thereby potentially increasing their risk of illness," Stager and colleagues suggested.

Although most cases of enteric fever in the US were linked to travel to southern Asia, the investigators found cases among travelers to other areas, including southeastern and western Asia, as well as South America and Central America.

"Travelers to high-risk destinations should be vaccinated against typhoid fever before traveling and follow safe food and water practices," they advise, noting that vaccination recommendations can be found on the CDC Travers' Health destination pages.

Reference

1. 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.