Nearly 8 in 10 Tested U.S. Typhoid Cases Resisted Ciprofloxacin, a Longtime First-Line Antibiotic

A CDC-led study published October 26 in JAMA Network Open reports that nearly eight in ten typhoid samples tested in the United States between 2016 and 2020 were not susceptible to ciprofloxacin, an antibiotic that has been a first-line treatment for the disease since the 1980s. The exact figure was 78.4%. For paratyphoid A, a closely related illness, it was 94.2%, according to CIDRAP's reporting.

The analysis covers 2,342 cases of enteric fever, the umbrella term for typhoid and paratyphoid, reported from 47 states. Researchers drew on national surveillance reports and on 1,635 bacterial samples tested through the CDC's National Antimicrobial Resistance Monitoring System. Because non-susceptibility to ciprofloxacin has been linked to poorer outcomes, the authors concluded that clinicians should avoid starting treatment with fluoroquinolones, the drug class that includes ciprofloxacin, for most travel-related cases, and should tailor therapy to laboratory results.

Most of these infections begin abroad. More than 80% of patients had traveled or lived outside the country in the 30 days before falling ill, and India, Pakistan and Bangladesh were the most common destinations. CIDRAP's summary puts the U.S. burden at about 5,700 enteric fever cases a year, against roughly 8 million worldwide.

Ciprofloxacin is not the only concern. Among typhoid samples, 5.5% were resistant to ceftriaxone, a commonly used intravenous antibiotic, and that resistance was largely seen in travelers to Pakistan. An outbreak of extensively drug-resistant (XDR) typhoid began there in 2016, according to the CDC's clinical overview. XDR typhoid resists ciprofloxacin, ceftriaxone and several older drugs. In February 2021 the CDC issued a health advisory about XDR infections in people who had not traveled, after cases appeared in U.S. residents with no trip abroad. In the new study, 11 of 67 XDR typhoid cases had no reported international travel.

The trend has been building for decades. The study reports that the share of U.S. typhoid samples not susceptible to ciprofloxacin rose from 12.0% in 1999 to 75.1% in 2023, which suggests the 2016 to 2020 findings still describe current conditions.

The study has limits. It is a cross-sectional analysis of laboratory and surveillance data, not a clinical trial, and it did not test how individual patients responded to each antibiotic. Non-susceptibility also covers both full resistance and reduced sensitivity. "Because resistance can evolve quickly, surveillance is important to detect emerging resistance," the authors wrote, calling for treatment guided by susceptibility testing and the patient's travel history. Options remain: the CDC's 2021 advisory said XDR samples were still susceptible to azithromycin and to carbapenems such as meropenem.

The people at greatest risk are often those visiting friends or relatives, many of whom do not seek health care before departing, according to CDC vaccine recommendations. Infections have occurred on trips shorter than a week. Typhoid spreads through contaminated food and water, with symptoms appearing 6 to 30 days after exposure: a fever that climbs over several days, fatigue, headache, loss of appetite and stomach pain. In some hospitalized patients it causes intestinal bleeding or a hole in the intestine, which can be life-threatening. About 1% to 4% of treated patients become carriers, shedding bacteria for a year or longer without symptoms.

Two vaccines are available in the U.S., an injection and a four-capsule oral series, each protecting roughly 50% to 80% of recipients. The shot should come at least two weeks before travel, and the capsules should be finished at least a week before possible exposure. Neither protects against paratyphoid, so food and water precautions and frequent handwashing still matter. Anyone with a fever during or after travel should see a clinician promptly, name the countries visited, and ask about blood cultures, which can identify typhoid and show which antibiotics will work. Leftover antibiotics or medicines bought abroad are not a substitute, since the wrong drug can delay a correct diagnosis.