In vitro susceptibility of zoliflodacin and solithromycin in Neisseria gonorrhoeae isolated in Republic of Korea from 2016 to 2018

Abstract

Background: Zoliflodacin (topoisomerase II inhibitor) and solithromycin (first fluoroketolide) are new drugs which are in clinical development for treatment of uncomplicated gonorrhea. In this study, we determined the in vitro activity of zoliflodacin and solithromycin in gonococcal isolates from Republic of Korea. Methods: A total of 250 isolates of N. gonorrhoeae collected throughout Republic of Korea from 2016 to 2018 were tested to determine MIC of therapeutic antimicrobials using CLSI agar dilution method. Results: Most isolates (86.4%, 234/250) were non-susceptible to penicillin G, tetracycline and ciprofloxacin, but all isolates were susceptible to ceftriaxone and spectinomycin. The MIC range for zoliflodacin and solithromycin were ≤0.015–0.12 mg/L and ≤0.015–0.5 mg/L, respectively. MIC50 and MIC90 were 0.03 and 0.06 mg/L for zoliflodacin and 0.06 and 0.12 mg/L for solithromycin. All isolates belonged to the wild-type MIC distribution for zoliflodacin and there were no cross-resistance between zoliflodacin and ciprofloxacin (also a topoisomerase II inhibitor). The azithromycin-resistant isolate with the highest MIC of azithromycin (32 mg/L) had the highest MIC of solithromycin (0.5 mg/L), illustrating cross-resistance between azithromycin and solithromycin at higher MICs. Conclusion: Zoliflodacin and solithromycin showed potent antimicrobial activity against contemporary multidrug-resistant N. gonorrhoeae isolates in Republic of Korea. However, the recently finished phase III clinical trial for solithromycin identified relatively many treatment failures. Zoliflodacin remains more promising and a multi-continental phase III clinical trial will be initiated in 2019