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OBJECTIVE: To report a case of typhoid fever contracted in Portugal in 1994 due to a Salmonella typhi isolate which had reduced susceptibility to fluoroquinolone (MIC 1 mg/L of ciprofloxacin) and high level resistance to nalidixic acid (MIC greater-than-or-equal 56 mg/L). METHODS: Molecular studies of reduced susceptibility to fluoroquinolones comprised complementation tests with a wild-type allele and sequencing directly from PCR products of the gyrA gene. RESULTS: Complementation tests and DNA sequencing showed that a mutation occurred in the gyrA gene of this clinical isolate, resulting in a substitution of phenylalanine for serine at position 83 of GyrA. CONCLUSIONS: Because quinolones may be regarded as a treatment of choice in typhoid fever, it seems important now to recommend cautious use of these drugs as first-line therapy and possibly use of nalidixic acid resistance as a marker for detection of 'first-step' resistance to fluoroquinolones in S. typhi.

This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

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