Susceptibility of Neisseria gonorrhoeae to Zoliflodacin and Quinolones in Hyogo Prefecture, Japan

Abstract

The DNA synthesis inhibitor zoliflodacin (ZFD) is expected to be effective against strains resistant to therapeutic agents for Neisseria gonorrhoeae infection. In addition to ZFD, we investigated the susceptibility of N. gonorrhoeae strains to ceftriaxone (CTRX), ciprofloxacin (CPFX), garenoxacin (GRNX), and sitafloxacin (STFX). Minimum inhibitory concentration values for ZFD and four other drugs were determined for 147 strains of N. gonorrhoeae isolated at medical institutions in Hyogo Prefecture, Japan, from 2015 to 2022. Amino acid alterations in gyrA, gyrB, parC, and parE were examined by polymerase chain reaction and sequencing analysis. Sequence type (ST) was determined for epidemiological analysis, and N. gonorrhoeae strains were classified. The non-susceptibility rate was not observed in CTRX. The lowest non-susceptibility rate was observed in ZFD (39.5%) compared to CPFX (80.3%), GRNX (83.7%), and STFX (65.3%) (all p < 0.0001). The most common amino acid alterations in gyrA and parC had non-susceptibility rates exceeding 80% to quinolones except ZFD, suggesting that these alterations may have influenced the resistance trend. STs were different between isolates in 2015 and those in 2020 and later. ZFD showed potent antimicrobial activity against N. gonorrhoeae strains that are highly resistant to quinolones. It may become a new option in the treatment of gonococcal infections.

Keywords: DNA gyrase; Neisseria gonorrhoeae; quinolones; susceptibility; topoisomerase IV; zoliflodacin (ZFD).

Figure 1

Annual trends of non-susceptibility rates of 147 N. gonorrhoeae strains to antibiotics. The results of the antimicrobial susceptibility testing of ciprofloxacin (CPFX) (a), garenoxacin (GRNX) (b), sitafloxacin (STFX) (c), and zoliflodacin (ZFD) (d) in N. gonorrhoeae strains show the rates of resistant (R) and intermediate (I) strains. All annual trends for the non-sensitivity rates were examined by the chi-square test, and each annual trend was compared among the 2015 and other years’ strains by the Bonferroni method adjustment (p < 0.0083 with a significant difference).