Typhoid Fever's Growing Antibiotic Resistance Alarms Experts

STANFORD, CA – Typhoid fever is reemerging as a formidable health threat as the bacterium Salmonella typhi develops resistance to nearly all known antibiotics, causing alarm among medical professionals worldwide.

Breaking: Rapid Spread of Resistant Strains

The speed at which highly-resistant strains of S. typhi have emerged and spread is a significant concern, according to Jason Andrews of Stanford University. This development underscores the urgent need for new treatment strategies.

Immediate Impact on Treatment

Modern treatments rely on antibiotics to kill the typhoid bacterium faster than it can mutate. However, this balance is shifting in favor of the microbe due to increasing antimicrobial resistance, often exacerbated by incomplete drug courses or incorrect prescriptions.

Genomic research on 3,489 isolates from India, Pakistan, Nepal, and Bangladesh reveals that resistant typhoid strains have replaced susceptible ones within just a few years.

Key Details Emerge: Resistance Mechanisms

Some typhoid isolates carry three mutations in the DNA-gyrase genes, significantly increasing the ciprofloxacin dose required, effectively removing a key outpatient treatment option. Third-generation cephalosporins, once frontline treatments, are also becoming ineffective.

A 2025 survey in Ahmedabad, India, identified a cluster resistant to ceftriaxone, ampicillin, ciprofloxacin, and trimethoprim-sulfamethoxazole, marking the largest hotspot of ceftriaxone-resistant typhoid identified to date.

Industry Response: Shrinking Antibiotic Options

Currently, azithromycin remains effective for oral administration, but rising minimum inhibitory concentrations in Pakistan and new resistant cases in the U.S. indicate potential future challenges. Intravenous carbapenems may become the last resort, though they are costly and scarce in many endemic areas.

By the Numbers: Vaccine Deployment

To combat the spread of resistant strains, three typhoid vaccines are globally licensed, with the conjugate vaccine suitable for infants as young as six months. The World Health Organization recommends the introduction of these vaccines in high-burden countries.

Pakistan, the first nation to include the vaccine in its routine schedule in 2019, has seen a decrease in childhood cases in vaccinated districts, buying time for antibiotic developments.

What Comes Next: Addressing Global Spread

The globalization of travel facilitates the spread of resistant strains. Genomic “family trees” have traced at least 59 intercontinental movements of resistant S. typhi since 1990, predominantly originating from South Asia.

In 2019, the CDC reported approximately 450 culture-confirmed typhoid cases in the U.S., nearly all linked to recent travel, emphasizing the need for rapid susceptibility testing.

Background Context: Surveillance and Policy

Continuous genomic surveillance is crucial to detect new resistant strains before they cross borders undetected. A 2022 study mapped nearly 8,000 S. typhi genomes, highlighting the need for more comprehensive data in low-resource settings.

Health policies must adapt to these changes, with countries experiencing rising resistance urged to introduce vaccines and modify treatment protocols proactively.

Expert Analysis: Clinical Recommendations

Full 10 to 14-day courses of azithromycin remain effective in most regions, but follow-up cultures are essential to prevent silent carriers from reintroducing the bacterium into communities.

Experts suggest combination therapy, such as azithromycin with meropenem, in severe cases to slow resistance, despite increased costs.

Regional Implications: Infrastructure Investments

While researchers explore new treatment avenues like oral β-lactamase inhibitors and phage therapy, the most significant gains come from improving basic infrastructure. Safe water, proper sanitation, and reliable refrigeration significantly reduce typhoid risk.