Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions

• Published in: Journal of travel medicine Vol. 30; no. 1
• Main Authors: Posen, H Joshua, Wong, Waison, Farrar, Daniel S, Campigotto, Aaron, Chan, Tiffany, Barker, Kevin R, Hagmann, Stefan H F, Ryan, Edward T, LaRocque, Regina C, Earl, Ashlee M, Worby, Colin J, Castelli, Francesco, Fumadó, Victoria Pérez, Britton, Philip N, Libman, Michael, Hamer, Davidson H, Morris, Shaun K
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 18-02-2023
• Subjects: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; Antiinfectives and antibacterials; Azithromycin; Blood culture; Carbapenems; Ceftriaxone; Ciprofloxacin; Diarrhea; Drug resistance; Epidemiology; Fever; Gene sequencing; Genomes; Humans; Pakistan - epidemiology; Phenotypes; Salmonella; Salmonella typhi; Sulfamethoxazole; Travel; Trimethoprim; Typhoid; Typhoid Fever - epidemiology; Vaccination; Vaccines; Vomiting; Waterborne diseases; Whole genome sequencing; Pakistan; Canada; travel-acquired infection; Typhoid fever; Pakistan; returned traveler; antimicrobial resistance
• ISSN: 1195-1982; 1708-8305
• DOI: 10.1093/jtm/taac086

Abstract
Background
Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use.
Methods
Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim–sulfamethoxazole.
Results
Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade.
Conclusions
XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.