How multidrug resistance in typhoid fever affects treatment options

Salmonella enterica serotype Typhi (S. Typhi) is an enteric pathogen that causes typhoid fever. The infection can be severe, with significant morbidity and mortality, requiring antimicrobial therapy. Cases of S. Typhi infection in the United States and other developed countries are often associated with travel to endemic regions. The empirical use of first-line drugs for therapy, including ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, has resulted in transmissible multidrug resistance. With the global increase in multidrug-resistant S. Typhi, use of ciprofloxacin, with excellent oral absorption, few side effects, and cost-effectiveness, has become popular for treatment. However, decreased ciprofloxacin susceptibility due to point mutations in the S. Typhi genes gyrA and/or parC has caused treatment failures, necessitating alternative therapeutic options. S. Typhi is typically genetically homogenous, with phylogenetic and epidemiological studies showing that identical clones and diverse S. Typhi types often coexist in the same geographic region. Studies investigating point mutations have demonstrated that selective pressure from empirical use of first-line drugs and fluoroquinolones has led to the global emergence of haplotype H-58. Antibiotic resistance is subject to high selective pressure in S. Typhi and thus demands careful use of antimicrobials.