What is already known about this topic?
Extensively drug-resistant (XDR) Salmonella Typhi causing a typhoid fever outbreak in Pakistan is susceptible only to azithromycin and carbapenems.
What is added by this report?
During 2006–2015, 79% of U.S. isolates from typhoid fever patients who traveled to Pakistan were fluoroquinolone nonsusceptible. During 2016–2018, typhoid fever was diagnosed in 29 U.S. patients with recent Pakistan travel; five had XDR Typhi.
What are the implications for public health practice?
Vaccination can help prevent typhoid fever. Fluoroquinolones should not be used for empiric treatment of typhoid fever patients who traveled to South Asia. Patients with travel to Pakistan should be treated with azithromycin for uncomplicated typhoid fever and with carbapenems for complicated disease.