Rising antimicrobial resistance in Salmonella Typhi and Paratyphi is shifting clinical protocols for enteric fever, with CDC investigators now emphasizing tailored antibiotic therapy over empirical treatment.
Data published in JAMA Network Open reveals that nearly 75% of US typhoid isolates are now resistant to fluoroquinolones, necessitating precise susceptibility testing before selecting therapeutic agents.
- Test Before You Treat: Because many strains of typhoid and paratyphoid fever are now resistant to standard antibiotics like fluoroquinolones, physicians must perform susceptibility testing to identify which drugs will actually kill the bacteria.
- Prioritize Pre-Travel Consults: Travelers visiting friends or relatives in high-risk regions—particularly South Asia—are at higher risk for resistant infections, often because they are less likely to seek professional pre-travel medical advice or vaccinations.
- Prevention is Primary: When traveling to regions with high antimicrobial resistance, vaccination is critical. Always adhere to strict food and water safety precautions, as these remain the most effective tools for preventing infection in areas where common medications may fail.
Resistance Trends in Enteric Fever
The clinical landscape for enteric fever has changed dramatically over the last two decades, Contagion Live reported this week. In 1999, only 12.0% of Typhi isolates were nonsusceptible to fluoroquinolones, a class of antibiotics once considered a gold standard for treatment. By 2023, that figure surged to 75.1%, rendering many traditional treatment pathways ineffective.
The research, led by C.H. Stager and colleagues, highlights that the threat is not uniform. Travelers returning from the Indian subcontinent—specifically Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka—face significantly higher odds of encountering multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains. For those returning from these regions, the odds of an XDR infection are 294.04 times higher than for travelers to other destinations.
Data Comparison of Resistance Patterns
| Strain Type | 1999 Prevalence | 2023 Prevalence | Clinical Significance |
|---|---|---|---|
| FQ-NS Typhi | 12.0% | 75.1% | Reduced efficacy of fluoroquinolones |
| FQ-NS Paratyphi | Lower (pre-2007) | 78.9%–96.0% | High resistance since 2007 |
| MDR Typhi | N/A (2016-2020 data) | 8.7% | Resistant to ampicillin, chloramphenicol, TMP-SMX |
VFR Travelers Face Higher Infection Risks than Immigrants
The study found a distinct epidemiological link between travel purpose and infection risk. Travelers visiting friends or relatives (VFR travelers) demonstrated higher odds of resistant infections compared to those traveling for immigration purposes. Stager and colleagues suggest that VFR travelers may be less likely to attend pre-travel health consultations, missing vital opportunities for vaccination and education on safe consumption practices.
“Travelers visiting friends or relatives may be less likely than other travelers to seek pre-travel advice or attend a pre-travel health care consultation, thereby potentially increasing their risk of illness.”
Stager and colleagues told Contagion Live. While southern Asia remains the primary region of concern, the investigation identified cases linked to travel in southeastern Asia, western Asia, South America, and Central America, indicating a broader geographical risk profile than previously prioritized.
Seek Medical Evaluation If Experiencing Fever or Abdominal Pain After Travel
Patients who have recently returned from international travel and experience persistent high fever, abdominal pain, or gastrointestinal distress should seek medical evaluation immediately. It is essential to disclose travel history to your primary care physician or local urgent care provider, as this informs the necessity of specific diagnostic testing.
“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.
There is no single “contraindication” for enteric fever treatment, but rather a clinical mandate: clinicians must avoid relying on empirical fluoroquinolone monotherapy if the patient has a recent history of travel to high-risk regions in South Asia. Treatment must be guided by laboratory results confirming the isolate’s susceptibility profile to ensure the chosen antimicrobial agent is effective against the specific strain.
The investigators emphasize that until susceptibility results are available, initial therapy must be carefully selected based on local and regional resistance patterns. The long-term trajectory of these pathogens remains a concern for public health authorities, as the rapid evolution of antimicrobial resistance continues to outpace the development of new, effective antibiotic therapies.
References
- 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.
