Relationship between mutations in parC and gyrA of clinical isolates of Streptococcus pneumoniae and resistance to ciprofloxacin and grepafloxacin.

The mechanisms of resistance to ciprofloxacin and grepafloxacin were studied in 54 clinical isolates of Streptococcus pneumoniae. Restriction fragment length polymorphism analysis following HinfI digestion was used with DNA sequencing to identify mutations in the quinolone resistance-determining regions (QRDRs) of the parC and gyrA 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 8-16mg/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 parC.