Table 1.

Recommendations for the Management of Extensively Drug-Resistant Typhoid Fever in the United States

General management considerations	Obtain a 30-day international travel historya from all patients with suspected or confirmed typhoid fever. Lack of international travel does not rule out a diagnosis of typhoid fever; Typhi can be acquired in the United States. Order blood cultures if typhoid fever is suspected; multiple cultures are usually needed. Bone marrow cultures have the highest sensitivity and may be considered for some patients (eg, those who have already started or completed a course of antimicrobial treatment). Stool, urine, and duodenal cultures may also be helpful. Order antimicrobial susceptibility testing for Typhi isolates and adjust antibiotic treatment accordingly. Vaccination is recommended for people in close contact with a typhoid carrier. Ask the patient if they have additional household members or other close contacts.
Selection of empiric treatment by country of exposureb	Pakistan	Patients are often infected with XDR Typhi. Consider prescribing a carbapenem (particularly if patients have severe or complicated illnessc) or azithromycin for empiric treatment.
	Iraq	Patients often have strains that are resistant or intermediate to ciprofloxacin; some strains are also resistant to ampicillin and ceftriaxone. Consider prescribing a carbapenem (particularly if patients have severe or complicated illnessc) or azithromycin for empiric treatment.
	Other countries	Most patients have strains that are susceptible to ceftriaxone and azithromycin, which remain appropriate empiric treatment options.
	No international travelb	Patients might be infected with XDR Typhi. Consider prescribing a carbapenem (particularly if patients have severe or complicated illnessc) or azithromycin for empiric treatment.
Treatment of known XDR Typhi	Treat patients with XDR Typhi infection with a carbapenem, azithromycin, or bothd. Treat patients with severe or complicated illnessc with a carbapenem, such as meropenem. Patients with uncomplicated illness may be treated with oral azithromycin alone.

Abbreviation: XDR, extensively drug-resistant.

The patient should be asked about any exposures outside of the United States even if these are not strictly travel related (ie, patients may be international citizens traveling to the United States, immigrants, or US citizens who live in border areas and commute). Nontravelers may be asked if they have close contacts such as household members who have recently traveled.

In the 30 days before illness onset.

Severe or complicated typhoid fever can include bacteremia with sepsis or shock, gastrointestinal complications (eg, intestinal perforation, peritonitis, intestinal hemorrhage, hepatitis), and neurologic complications (eg, encephalopathy).

Case reports have suggested that patients who do not improve on a carbapenem alone may benefit from the addition of a second antibiotic, such as azithromycin.