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Typhi infection in the United States and other developed countries are often associated with travel to endemic regions. The empirical use of first\u2010line drugs for therapy, including ampicillin, chloramphenicol, and trimethoprim\/sulfamethoxazole, has resulted in transmissible multidrug resistance. With the global increase in multidrug\u2010resistant <jats:italic>S<\/jats:italic>. Typhi, use of ciprofloxacin, with excellent oral absorption, few side effects, and cost\u2010effectiveness, has become popular for treatment. However, decreased ciprofloxacin susceptibility due to point mutations in the <jats:italic>S<\/jats:italic>. Typhi genes <jats:italic>gyrA<\/jats:italic> and\/or <jats:italic>parC<\/jats:italic> has caused treatment failures, necessitating alternative therapeutic options. <jats:italic>S<\/jats:italic>. Typhi is typically genetically homogenous, with phylogenetic and epidemiological studies showing that identical clones and diverse <jats:italic>S<\/jats:italic>. Typhi types often coexist in the same geographic region. Studies investigating point mutations have demonstrated that selective pressure from empirical use of first\u2010line drugs and fluoroquinolones has led to the global emergence of haplotype H\u201058. Antibiotic resistance is subject to high selective pressure in <jats:italic>S<\/jats:italic>. 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