Department of Microbiology, and Department of Dermatology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
J Antimicrob Chemother. 2022 Aug 25;77(9):2461-2469. doi: 10.1093/jac/dkac202.
Ceftriaxone therapy for gonorrhoea has become under increasing pressure due to waning susceptibility levels and emergence of high-level resistant strains such as the FC428 clone. Moenomycin was recently identified to display potent anti-gonococcal activity against some reference strains. Therefore, the aim of this study was to investigate moenomycin in vitro and in vivo antimicrobial activity.
Moenomycin in vitro antimicrobial activity was investigated against 575 clinical isolates, including strains associated with the FC428 clone, using the agar dilution method. Moenomycin in vivo activity was investigated in a mouse vaginal tract gonococcal infection model.
The moenomycin MIC range for the strain collection was 0.004-0.06 mg/L, with a MIC50 of 0.016 mg/L and a MIC90 of 0.03 mg/L. The correlation between moenomycin and ceftriaxone susceptibility levels was poor (R = 0.13), while the fractional inhibitory concentration index (FICI) resulted in indifference for all tested strains. Therefore, development of cross-resistance between moenomycin and ceftriaxone is unlikely for N. gonorrhoeae. Determination of the moenomycin mode of activity against N. gonorrhoeae by time-kill assays showed that moenomycin is bactericidal, with over 104-fold inactivation observed after 4 h exposure. Finally, an intramuscular moenomycin dose of 10 mg/kg given on 2 consecutive days was able to clear a gonococcal infection in a mouse vaginal tract infection model within 1-3 days after the second dose, which was significantly faster than for mice treated with the vehicle control (P < 0.0001).
Moenomycin displays potent in vitro and in vivo antimicrobial activity against N. gonorrhoeae, warranting further exploration as alternative therapy.
由于淋病奈瑟菌的敏感性水平下降以及高水平耐药菌株（如 FC428 克隆）的出现，头孢曲松治疗受到越来越大的压力。莫能霉素最近被鉴定对一些参考菌株具有强大的抗淋病奈瑟菌活性。因此，本研究旨在研究莫能霉素的体外和体内抗菌活性。
采用琼脂稀释法，检测莫能霉素对 575 株临床分离株的体外抗菌活性，包括与 FC428 克隆相关的菌株。在小鼠阴道淋病奈瑟菌感染模型中研究莫能霉素的体内活性。
该菌株的莫能霉素 MIC 范围为 0.004-0.06mg/L，MIC50 为 0.016mg/L，MIC90 为 0.03mg/L。莫能霉素与头孢曲松敏感性水平之间的相关性较差（R=0.13），而部分抑菌浓度指数（FICI）对所有测试菌株均无差异。因此，莫能霉素和头孢曲松之间不太可能产生交叉耐药性。通过时间杀伤试验确定莫能霉素对淋病奈瑟菌的作用模式，表明莫能霉素具有杀菌作用，暴露 4 小时后观察到超过 104 倍的失活。最后，连续 2 天肌肉注射 10mg/kg 莫能霉素，在第 2 次给药后 1-3 天内可清除小鼠阴道感染模型中的淋病奈瑟菌感染，明显快于给予载体对照的小鼠（P<0.0001）。
莫能霉素对淋病奈瑟菌具有强大的体外和体内抗菌活性，值得进一步探索作为替代治疗方法。
