Susceptibility Trends of Zoliflodacin against Multidrug-Resistant Clinical Isolates in Nanjing, China, 2014 to 2018.

Previously, we reported the potent activity of a novel spiropyrimidinetrione, zoliflodacin, against isolates collected in 2013 from symptomatic men in Nanjing, China. Here, we investigated trends of susceptibilities to zoliflodacin in 986 isolates collected from men between 2014 and 2018. isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in the , , , , and genes were determined by PCR and sequencing. The MICs of zoliflodacin ranged from ≤0.002 to 0.25 mg/liter; the overall MIC and MIC were 0.06 mg/liter and 0.125 mg/liter, respectively, in 2018, increasing 2-fold from 2014. However, the percentage of isolates with lower zoliflodacin MICs declined in each year sequentially, while the percentage with higher MICs increased yearly ( ≤ 0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥ 1 mg/liter); 21.2% (209/986) were resistant to azithromycin (≥1 mg/liter), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) were tetracycline-resistant (TRNG), and 19.4% (191/986) were multidrug-resistant (MDR) isolates. 202 isolates with the lowest (≤0.002 to 0.015 mg/liter) and highest (0.125 to 0.25 mg/liter) zoliflodacin MICs were quinolone resistant with double or triple mutations in ; 193/202 (95.5%) also had mutations in There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; an S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin continues to have excellent activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin, and extended-spectrum cephalosporins.