REDUCED CLINICAL EFFICACY OF PAZUFLOXACIN AGAINST GONORRHEA DUE TO HIGH PREVALENCE OF QUINOLONE-RESISTANT ISOLATES WITH THE GYRA MUTATION

Forty-two men with gonococcal urethritis were treated with an oral dos age of 200 mg of pazufloxacin, a new fluoroquinolone, three times dail y for 3 days. Only 28 of the 42 men (66.7%) had negative culture resul ts for Neisseria gonorrhoeae during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic susceptibility testing and DNA sequ encing, In 26 of the 41 isolates (63.4%), GyrA mutations with or witho ut ParC mutations were identified, Among the 26 isolates, 23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2 contain ed three mutations including double GyrA and single: ParC mutations. A single Ser-91-to-Phe mutation, which was detected in 14 of the 26 iso lates, was the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp-95 to Asn dr Gly mutation in GyrA, All three isol ates with two or three mutations contained the Ser-91-to-Phe GyrA muta tion. Eleven of the 14 isolates with the single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three mutations persisted after pazufloxacin treatment, On the other hand, all 15 wild-type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were e radicated. The mean MIC of pazufloxacin for mutants with the single Se r-91-to-Phe mutation in GyrA was 66-fold higher than that for the wild type. The results obtained in this study suggest that a high prevalen ce of fluoroquinolone-resistant gonococcal isolates with the Ser 91-to -Phe mutation in GyrA reduced the efficacy of pazufloxacin as treatmen t for gonococcal urethritis.