<i>In-vitro</i> Activities of Zoliflodacin and Solithromycin Against <i>Neisseria gonorrhoeae</i> Isolates from Korea

Novel antimicrobial agents are continually developed to address the global threat of multidrug-resistant <i>Neisseria gonorrhoeae</i>. Promising candidates include zoliflodacin and, possibly, solithromycin. We evaluated their <i>in-vitro</i> activities against gonococcal isolates collected in Korea. In total, 250 <i>N. gonorrhoeae</i> isolates obtained across Korea between 2016 and 2018 were used to determine the minimum inhibitory concentrations (MICs) of 10 therapeutic agents using the CLSI agar dilution method. Most isolates (94.8%, 237/250) demonstrated non-susceptibility to penicillin G, tetracycline, and ciprofloxacin, and susceptibility to ceftriaxone and spectinomycin was substantially high. The half-maximal IC (MIC50) and 90% IC (MIC90) values for zoliflodacin were 0.03 and 0.06 μg/mL, respectively; 0.06 and 0.12 μg/mL, respectively, for solithromycin; and 0.03 and 0.12 μg/mL, respectively, for ceftriaxone. Notably, no cross-resistance was observed between zoliflodacin and ciprofloxacin, despite both targeting DNA topoisomerase II enzymes. Zoliflodacin and solithromycin demonstrated significant <i>in-vitro</i> activity against multidrug-resistant <i>N. gonorrhoeae</i> isolates, and zoliflodacin has shown non-inferiority to ceftriaxone/azithromycin dual therapy in a clinical phase 3 trial. Collectively, our findings highlight the potential of zoliflodacin as a novel therapeutic agent for gonococcal infections, particularly in the context of rising multidrug resistance, and highlight the need for continued surveillance and development of alternative antimicrobial strategies.