Salmonella typhiin the past decade: learning to live with resistance.

Sir—Salmonella typhi, the agent that causes enteric fever, continues to be the isolate most frequently associated with community-acquired bacteremia at our institute (a tertiary care center in Mumbai, India). For decades, chloramphenicol was the antibiotic of choice for treatment of enteric fever, but the widespread emergence of S. typhi with plasmid-mediated resistance to multiple drugs, including chloramphenicol, cotrimoxazole, and amoxicillin, necessitated the search for other options. Such resistance is conferred by the presence of a 100-megadalton plasmid. During the past 10 years, the plasmidmediated resistance of S. typhi strains decreased from 74% in 1990 to 40% in 1994; however, it stabilized at 46% in the year 2000 (table 1). Fluoroquinolones were introduced in Mumbai, India, in 1989, and, during the past decade, we have documented an increase in the MICs of ciprofloxacin [1]. In vitro resistance to nalidixic acid has emerged as a predictor of clinical failure of fluoroquinolone therapy [2], despite the susceptibility of S. typhi strains to ciprofloxacin (as seen on disk diffusion). For these strains, the equivalent MIC breakpoints for ciprofloxacin are 0.5–1 mg/mL. In light of the increasing number of persons with clinical treatment failure (e.g., persistent fever for 17 days while receiving fluoroquinolones) and of those with microbiological treatment failure (e.g., positive culture results obtained while receiving fluoroquinolones), perhaps the equivalent MIC breakpoint needs to be lowered from 1 mg/mL. Ceftriaxone, a third-generation cephalosporin, is the present standard treatment for typhoid fever in Mumbai. We have not encountered any resistance associated with the use of ceftriaxone. However, patients have had relapses while following 3–5-day regimens of ceftriaxone. Although we analyzed 50 representative strains for production of extended-spectrum b-lactamase, we did not find any evidence of such production. In our hospital, we use the following regimens for the treatment of enteric fever: