Lagacé-Wiens P R S, Adam H J, Laing N M, Baxter M R, Martin I, Mulvey M R, Karlowsky J A, Hoban D J, Zhanel G G
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, 771 Bannatyne Ave., Winnipeg, Manitoba, Canada, R3E 3N4.
Department of Clinical Microbiology, Diagnostic Services Manitoba, L4025-409 Taché Ave., Winnipeg, Manitoba, Canada, R2H 2A6.
J Antimicrob Chemother. 2017 Aug 1;72(8):2273-2277. doi: 10.1093/jac/dkx147.
The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections.
To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N. gonorrhoeae resistant to one or multiple antimicrobials.
The MICs of conventional anti-gonococcal antimicrobials (penicillin, ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and spectinomycin) and alternative antimicrobials (ertapenem, gentamicin, netilmicin, tigecycline, eravacycline, fosfomycin, linezolid, ceftazidime/avibactam and ceftaroline) were determined by agar dilution.
Ertapenem and the novel cephalosporins demonstrated similar MIC values to the third-generation cephalosporins, but increased MICs were observed for isolates with increased cefixime and ceftriaxone MICs. Tigecycline and eravacycline had MIC values below expected serum concentrations for all isolates tested. The aminoglycosides gentamicin and netilmicin were generally more potent than spectinomycin, with netilmicin demonstrating the greatest potency. Fosfomycin MICs were elevated compared with other agents, but remained within the MIC range for susceptible organisms, while linezolid MICs were generally higher than those for organisms considered resistant.
Among potentially therapeutically useful alternative agents, the aminoglycosides, eravacycline, tigecycline and fosfomycin had good in vitro activity. The novel cephalosporins and ertapenem had comparable activity to cefixime and ceftriaxone.
耐多药淋病奈瑟菌在全球的流行率正在上升,这是一场公共卫生突发事件。新的抗淋球菌药物的研发和获批可能需要数年时间。作为开发新抗菌药物的并行方法,对目前已获许可但未广泛用于治疗淋病的抗菌药物进行实验室和临床评估,可能为淋病感染的治疗提供新的选择。
确定9种可供选择的、目前已获许可且处于后期研发阶段的、有潜力治疗淋球菌感染的抗菌药物对112株对一种或多种抗菌药物耐药的淋病奈瑟菌临床分离株的体外活性。
采用琼脂稀释法测定常规抗淋球菌抗菌药物(青霉素、头孢曲松、头孢克肟、阿奇霉素、环丙沙星、四环素和大观霉素)以及可供选择的抗菌药物(厄他培南、庆大霉素、奈替米星、替加环素、依拉环素、磷霉素、利奈唑胺、头孢他啶/阿维巴坦和头孢洛林)的最低抑菌浓度(MIC)。
厄他培南和新型头孢菌素的MIC值与第三代头孢菌素相似,但头孢克肟和头孢曲松MIC值升高的分离株的MIC值也有所增加。替加环素和依拉环素对所有测试分离株的MIC值均低于预期血清浓度。氨基糖苷类药物庆大霉素和奈替米星通常比大观霉素更有效,奈替米星的效力最强。与其他药物相比,磷霉素的MIC值有所升高,但仍在敏感菌的MIC范围内,而利奈唑胺的MIC值通常高于被认为耐药的菌株。
在具有潜在治疗作用的可供选择的药物中,氨基糖苷类药物、依拉环素、替加环素和磷霉素具有良好的体外活性。新型头孢菌素和厄他培南的活性与头孢克肟和头孢曲松相当。