Treatment failure in typhoid fever with ciprofloxacin susceptible Salmonella enterica Serotype Typhi

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Fluoroquinolones are considered the most effective drugs for the treatment of typhoid fever and hence are widely used in the empiric treatment of acute undifferentiated febrile illnesses in India. Recent reports of Salmonella enterica serotype Typhi ( S. Typhi) strains with increasing minimum inhibitory concentration (MIC) of ciprofloxacin have raised the fear of potential treatment failures. In this case series of 109 consecutive patients hospitalized with typhoid fever ( S. Typhi grown from blood), we documented clinical failure (fever persisting >6 days) in 25 of 46 (54.3%) adults who could be evaluated. Among these, eight (17.4%) had microbiological failure ( S. Typhi recovered from blood after 6 days of ciprofloxacin therapy) despite adequate serum ciprofloxacin levels, and all required alternative drugs for treatment. These 8 S. Typhi strains, although susceptible to ciprofloxacin (MIC < 1 μg/mL) (NCCLS 2000), had MICs (median MIC 0.5 μg/mL) that were increased 15-fold compared to S. Typhi strains from patients with typhoid fever seen at our center in 1995 (median MIC 0.032 μg/mL), and were nalidixic acid resistant S. Typhi (NARST) (MIC ≥32 μg/mL). The poor treatment outcomes with ciprofloxacin therapy in patients infected with NARST strains that exhibit an increased ciprofloxacin MIC call for a need to revise the ciprofloxacin breakpoints for S. Typhi.