耐药淋病奈瑟菌对公众健康构成紧迫威胁。最近,西他沙星,新一代氟喹诺酮,已显示出对耐药淋病奈瑟菌的高体外活性。然而,其在临床分离株中的有效性数据仍然有限.在这项研究中,我们从上海21家医院收集了507株淋病奈瑟菌,中国,在2020年和2021年。抗菌药物敏感性试验显示西他沙星最低抑菌浓度(MIC)呈双峰分布,范围从<0.004到2mg/L西他沙星的MIC50和MIC90分别为0.125mg/L和0.5mg/L,分别,比环丙沙星(4mg/L和8mg/L,分别)。西他沙星对头孢曲松耐药的分离株表现出很高的体外活性,阿奇霉素,或者两者兼而有之。值得注意的是,在西他沙星敏感性降低(MIC≥MIC90)的分离株中,83.7%(36/43)被鉴定为序列类型(ST)8123。进一步的系统发育分析表明,ST8123已经演变成两个亚进化支,指定为子分化-I和子分化-II。大多数分离株(80%,36/45)在亚分化I内表现出对西他沙星的敏感性降低。相比之下,发现来自subclade-II的所有分离株对西他沙星敏感.随后的基因组研究表明,GyrA-S91F,D95Y,和ParC-S87N突变,这些都是在ST8123分枝-I中唯一发现的,可能与西他沙星敏感性降低有关。我们的研究表明,西他沙星是对抗耐药淋病奈瑟菌的有前途的抗生素。然而,由于出现了敏感性降低的克隆,因此在西他沙星治疗淋病奈瑟菌感染的临床应用中应谨慎。
Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. gonorrhoeae isolates from 21 hospitals in Shanghai, China, during 2020 and 2021. Antimicrobial susceptibility testing revealed that sitafloxacin minimum inhibitory concentrations (MICs) exhibited a bimodal distribution, ranging from <0.004 to 2 mg/L. The MIC50 and MIC90 for sitafloxacin were 0.125 mg/L and 0.5 mg/L, respectively, which are 32 and 16 times lower than those for ciprofloxacin (4 mg/L and 8 mg/L, respectively). Sitafloxacin demonstrated high in vitro activity against isolates resistant to either ceftriaxone, azithromycin, or both. Notably, among the isolates with reduced sitafloxacin susceptibility (MIC ≥ MIC90), 83.7% (36/43) were identified as sequence type (ST) 8123. Further phylogenetic analysis showed that ST8123 has evolved into two subclades, designated as subclade-I and subclade-II. A majority of the isolates (80%, 36/45) within subclade-I exhibited reduced susceptibility to sitafloxacin. In contrast, all isolates from subclade-II were found to be susceptible to sitafloxacin. Subsequent genomic investigations revealed that the GyrA-S91F, D95Y, and ParC-S87N mutations, which were exclusively found in ST8123 subclade-I, might be linked to reduced sitafloxacin susceptibility. Our study reveals that sitafloxacin is a promising antibiotic for combating drug-resistant N. gonorrhoeae. However, caution is advised in the clinical application of sitafloxacin for treating N. gonorrhoeae infections due to the emergence of a clone exhibiting reduced susceptibility.