Emergence of <i>Neisseria gonorrhoeae</i> Clone with Reduced Susceptibility to Sitafloxacin in China: An In Vitro and Genomic Study

Drug-resistant <i>Neisseria gonorrhoeae</i> poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant <i>N. gonorrhoeae</i>. However, data on its effectiveness in clinical isolate...

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Main Authors: Meiping Ye (Author), Linxin Yao (Author), Xinying Lu (Author), Fangyuan Ding (Author), Danyang Zou (Author), Tingli Tian (Author), Yi Lin (Author), Zhen Ning (Author), Jianping Jiang (Author), Pingyu Zhou (Author)
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Published: MDPI AG, 2024-05-01T00:00:00Z.
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Summary:Drug-resistant <i>Neisseria gonorrhoeae</i> poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant <i>N. gonorrhoeae</i>. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 <i>N. gonorrhoeae</i> 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 MIC<sub>50</sub> and MIC<sub>90</sub> 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 ≥ MIC<sub>90</sub>), 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 <i>N. gonorrhoeae</i>. However, caution is advised in the clinical application of sitafloxacin for treating <i>N. gonorrhoeae</i> infections due to the emergence of a clone exhibiting reduced susceptibility.
Item Description:10.3390/antibiotics13050468
2079-6382