Background Fluoroquinolone-resistance in Neisseria gonorrhoeae is spreading in the world and almost 80% of N. gonorrhoeae strains are resistant to fluoroquinolones in Japan. It is known that the resistance to fluoroquinolones is closely related to genetic mutations of quinolone-resistance determining regions (QRDR) on gyrase genes such as gyrA or parC. In 2009, the first national surveillance of antimicrobial susceptibilities of N. gonorrhoeae was performed in Japan. In this surveillance, we found that sitafloxacin, one of newer fluoroquinolones, had a strong activity to ciprofloxacin-resistant N. gonorrhoeae strains. The MIC90 of ciprofloxacin or sitafloxacin were 16 μg/ml or 0.25 μg/ml, respectively.

Purpose In this study, the relationship between genetic mutations of QRDR and antimicrobial susceptibilities of sitafloxacin against ciprofloxacin-resistant N. gonorrhoeae strains was examined.

Methods The subjects were 12 N. gonorrhoeae strains which were gotten by the Japanese national surveillance by three Japanese societies including the Japanese Association of Infectious Diseases, the Japanese Society of Chemotherapy and the Japanese Society of Clinical Microbiology. MICs of sitafloxacin to these 12 strains were more than 2 μg/ml, but MICs of sitafloxacin to these strains were less than 0.125 μg/ml. The base sequence of QRDR on gyrA or parC genes of these strains were examined

Results On QRDRof gyrA of 12 strains, mutations of 2 amino-acids were found, such as Ser91to Phe, Asp95 to Ala or Asp95 to Gly. Regarding parC gene, mutations of 4 amino-acids were found, such as Asp86 to Asn in 1 strain, Ser87 to Asn in 6 strains, Ser87 to Arg in 5 strains, Glu91 to Lys, Gln or Gly in 3 strains and Ala123 to Ser in 3 strains.

Conclusion Sitafloxacin had a strong activity to ciprofloxacin-resistant N. gonorrhoeae which had at least more than 3 mutations of amino-acids on QRDR on gyrA and parC genes.