Association between proline-requiring auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Japan.

Abstract

We examined the association between auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Fukuoka, Japan, and investigated whether the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates was caused by the dissemination of the same clone in the community. We examined the antimicrobial susceptibility of 294 N. gonorrhoeae, isolates obtained during three different periods in Fukuoka, Japan, and 89 isolates of N. gonorrhoeae, classified by the presence of amino-acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA and ParC proteins, to various agents, and we examined the auxotypes of the isolates. In 22 isolates with amino-acid substitutions within QRDRs in GyrA and ParC, pulsed-field gel electrophoresis analysis was performed. The proportion of fluoroquinolone-resistant isolates (ciprofloxacin, minimum inhibitory concentration [MIC] > or = 1 microg/ml) in 1998 (23.9%) was significantly higher than that in 1992-1993 (0%). The proportion of proline-requiring isolates increased significantly, from 4.4% in 1992-1993 to 54.5% in 1998. The ciprofloxacin MIC90 for the proline-requiring isolates were 32- and 128-fold, respectively, higher than those for the prototrophic isolates and the arginine-requiring isolates. The proportion of isolates with amino-acid substitutions within the QRDRs in GyrA and ParC in the proline-requiring group (55.5%) was significantly higher than that in the prototrophic group (0%). Of the 22 isolates with amino-acid substitutions within the QRDRs in GyrA and ParC, 16 showed the same pulsed-field gel electrophoresis pattern. These results suggest that a close association exists between the increase in the proline-requiring isolates and the increase in the fluoroquinolone-resistant isolates in the gonococci isolated in Fukuoka, and that the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates with GyrA and ParC substitutions may be mainly caused by the dissemination of a single clone in the community.