By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: Nine patients in the United States with no travel history had typhoid fever due to extensively drug-resistant Salmonella Typhi.

SOURCE: Centers for Disease Control and Prevention. Official Health Advisory. Extensively drug-resistant Salmonella Typhi infections among U.S. residents without international travel. Health Alert Network. Feb. 12, 2021, 1:00 PM ET, CDCHAN-00439.

The emergence of extensively drug-resistant (XDR) Salmonella enterica ssp. enterica serovar Typhi in Pakistan has led to large numbers of cases in that country.1 In addition, cases have been seen within a number of countries in travelers from Pakistan. The Centers for Disease Control and Prevention (CDC) now reports nine cases of XDR Salmonella Typhi in the United States that occurred in the absence of any international travel history.

Of the 71 reports received by the CDC of patients with XDR Salmonella enterica ssp. enterica serovar Typhi infection as of Jan. 14, 2021, 67 had a known travel history. Culture specimens from the 71 had been obtained between February 2018 and mid-November 2020. Fifty-eight (87%) of these had traveled to Pakistan in the 30 days prior to the onset of illness. However, nine (13%) patients had not traveled outside the United States. These cases were identified in six states: three in New York, two in California, and one each in Illinois, Maryland, New Jersey, and Texas. Positive specimens had been identified in eight of the nine during the 2020 calendar year. The antimicrobial susceptibility patterns of the nine isolates were identical to those described for XDR Typhi in Pakistan. No epidemiologic linkages among the cases were identified by the CDC.


International travel, especially to South Asia, is a known risk factor for infection due to enteric pathogens with resistance to a number of antibiotics. Antibiotic resistance of Salmonella Typhi and paratyphi recovered from travelers of worldwide origin and identified in the GeoSentinel system was described recently by Hagmann and colleagues.2 The majority of the infections were acquired in South Asia. None of the 889 were XDR. Among the Salmonella Typhi for which the information was available, 65% were non-susceptible to ciprofloxacin, 50% were non-susceptible to ampicillin, 13% were non-susceptible to trimethoprim-sulfamethoxazole, 8% were non-susceptible to macrolides, 1.5% (representing only two isolates) were non-susceptible to third-generation cephalosporins. All were susceptible to carbapenems.

The XDR Salmonella Typhi that originated in Pakistan were characterized by resistance to ceftriaxone, ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole. Fortunately, the isolates were susceptible to azithromycin (although some recent isolates have been resistant to azithromycin) and to carbapenems.

The CDC makes the following recommendations for empiric therapy prior to the results of susceptibility testing. If the patient has traveled to Pakistan in the previous 30 days, initiate therapy with a carbapenem or azithromycin. For those with recent travel to Iraq, since it can be anticipated that most isolates will be resistant to or have reduced susceptibility to ciprofloxacin and that some strains are resistant to ampicillin and ceftriaxone, the recommendation again is to empirically use a carbapenem or azithromycin. Most patients who have not traveled recently to Pakistan or Iraq can be given ceftriaxone. Despite this, it is necessary to keep in mind that, although currently very rare, patients without a travel history may be infected with XDR Salmonella Typhi as were the nine reported by the CDC.


  1. Hussain A, Satti L, Hanif F, et al. Typhoidal Salmonella strains in Pakistan: An impending threat of extensively drug-resistant Salmonella Typhi. Eur J Clin Microbiol Infect Dis 2019;38:2145-2149.
  2. Hagmann SHF, Angelo KM, Huits R, et al. Epidemiological and clinical characteristics of international travelers with enteric fever and antibiotic resistance profiles of their isolates: A GeoSentinel analysis. Antimicrob Agents Chemother 2020;64:e01084-20.