Correlation of in vitro susceptibilities to newer quinolones of naturally occurring quinolone-resistant Neisseria gonorrhoeae strains with changes inGyrA and ParC

The in vitro activities of ciprofloxacin, trovafloxacin, moxifloxacin, and grepafloxacin against 174 strains of Neisseria gonorrhoeae isolated in Sydn ey, Australia, were determined. The strains included 84 quinolone-less-sens itive and -resistant N. gonorrhoeae (QRNG) strains for which ciprofloxacin MICs were in the range of 0.12 to 16 mug/ml. The QRNG included strains isol ated from patients whose infections were acquired in a number of countries, mostly in Southeast Asia. The gyrA and parC quinolone resistance-determini ng regions (QRDR) of 18 selected QRNG strains were sequenced, and the amino acid mutations observed were related to the MICs obtained. The activities of moxifloxacin and grepafloxacin against QRNG were comparable to that of c iprofloxacin. Trovafloxacin was more active than the other quinolones again st some but not all of the QRNG strains. Increments in ciprofloxacin resist ance occurred in a step-wise manner with point mutations initiated in gyrA resulting in amino acid alterations Ser91-to-Phe, Ser91-to-Tyr, Asp95-to-Gl y, and Asp95-to-Asn, Single gvrA changes correlated with ciprofloxacin MICs in the range 0.12 to 1 mug/ml. The Ser91 changes in GyrA were associated w ith higher MICs and further QRDR changes. QRNG strains for which ciprofloxa cin MICs were greater than 1 mug/ml had both gyrA and parC QRDR point mutat ions. ParC alterations were seen in these isolates only in the presence of GyrA changes and comprised amino acid changes Asp86-to-Asn, Ser87-to-Asn, S er87-to-Arg, Ser88-to-Pro, Glu91-to-Lys, and Glu91-to-Gln, QRNG strains for which MICs were in the higher ranges had double GyrA mutations, but again only with accompanying ParC alterations. Not only did the nature and combin ation of GyrA and ParC changes influence the incremental increases in cipro floxacin MICs, but they seemingly also altered the differential activity of trovafloxacin. Our findings suggest that the newer quinolones of the type examined are unlikely to be useful replacements for ciprofloxacin in the tr eatment of gonorrhea, particularly where ciprofloxacin MICs are high or whe re resistance is widespread.