Susceptibility Trends of Zoliflodacin against Multidrug-Resistant Neisseria gonorrhoeae Clinical Isolates in Nanjing, China, 2014 to 2018.
Susceptibility Trends of Zoliflodacin against Multidrug-Resistant Neisseria gonorrhoeae Clinical Isolates in Nanjing, China, 2014 to 2018.
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DOI：
10.1128/aac.00863-20
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发表时间：
2021-02-17
影响因子：
4.9
通讯作者：
Rice PA
中科院分区：
文献类型：
--
作者：
Le W;Su X;Lou X;Li X;Gong X;Wang B;Genco CA;Mueller JP;Rice PA
此前，我们报道了一种新型螺嘧啶三酮（zoliflodacin）对 2013 年从中国南京有症状男性中收集的淋病奈瑟菌分离株具有有效活性。在这里，我们调查了 2014 年至 2018 年间从男性收集的 986 株分离株对佐利氟达星的敏感性趋势。测试了淋病奈瑟菌分离株对佐利氟达星和其他七种抗生素的敏感性。此前，我们报道了一种新型螺嘧啶三酮（zoliflodacin）对 2013 年从中国南京有症状男性中收集的淋病奈瑟菌分离株具有有效活性。在这里，我们调查了 2014 年至 2018 年间从男性收集的 986 株分离株对佐利氟达星的敏感性趋势。测试了淋病奈瑟菌分离株对佐利氟达星和其他七种抗生素的敏感性。通过 PCR 和测序确定 gyrA、gyrB、parC、parE 和 mtrR 基因的突变。唑利氟达星的 MIC 范围为 ≤0.002 至 0.25mg/L； 2018年总体MIC50和MIC90分别为0.06毫克/升和0.125毫克/升，比2014年增加了2倍。然而，唑利氟达星MIC较低的菌株比例逐年下降，而MIC较高的菌株比例逐年上升（P≤≤0.00001）。所有分离株均对奇霉素敏感，但对环丙沙星耐药（MIC≥1mg/L）； 21.2% (209/986) 对阿奇霉素耐药 (≥1mg/L)，43.4% (428/986) 为产青霉素酶淋病奈瑟菌 (PPNG)，26.9% (265/986) 为耐四环素淋病奈瑟菌 (TRNG)，19.4% (191/986) 是多重耐药 (MDR) 分离株。唑利氟达星 MIC 最低（≤0.002 至 0.015 毫克/升）和最高（0.125 至 0.25 毫克/升）的 202 株分离株具有喹诺酮耐药性，且有 gyrA 双或三突变； 193/202 (95.5%) 也有 parC 突变。在 143 株具有较高唑利氟达星 MIC 的分离株中，未发现 GyrB 中的 D429N/A 和/或 K450T 突变；在一个分离株中发现了 GyrB 的 S467N 突变。我们报告说，佐利氟达星对临床淋球菌分离株（包括对环丙沙星、阿奇霉素和广谱头孢菌素具有高水平耐药性的淋球菌分离株）仍然具有优异的体外活性。
Previously, we reported the potent activity of a novel spiropyrimidinetrione, zoliflodacin, against Neisseria gonorrhoeae 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. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Previously, we reported the potent activity of a novel spiropyrimidinetrione, zoliflodacin, against Neisseria gonorrhoeae 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. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in the gyrA, gyrB, parC, parE, and mtrR genes were determined by PCR and sequencing. The MICs of zoliflodacin ranged from ≤0.002 to 0.25 mg/liter; the overall MIC50 and MIC90 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 (P ≤ 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 N. gonorrhoeae (PPNG), 26.9% (265/986) were tetracycline-resistant N. gonorrhoeae (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 gyrA; 193/202 (95.5%) also had mutations in parC. 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 in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin, and extended-spectrum cephalosporins.