The mechanisms of resistance to ciprofloxacin and grepafloxacin were studied in 54 clinical isolates of . Restriction fragment length polymorphism analysis following fl digestion was used with DNA sequencing to identify mutations in the quinolone resistance-determining regions (QRDRs) of the and genes. Ciprofloxacin MICs up to 16 mg/L were not associated with mutations to these genes in approximately half of the isolates. In other isolates, moderate levels of ciprofloxacin resistance (MIC 8-16 mg/L) were associated with an alteration of ParC, most commonly entailing replacement of serine-79 by phenylalanine. High-level ciprofloxacin resistance (MIC 32–128 mg/L) entailed the additional mutation of GyrA with substitution of serine-83 by phenylalanine. Grepafloxacin MICs >4 mg/L were associated with this GyrA mutation alone; no relationship was detected between grepafloxacin MICs and mutation of the QRDR of .


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