Barbee Lindley A, Soge Olusegun O, Holmes King K, Golden Matthew R
Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, USA Public Health - Seattle & King County HIV/STD Program, Seattle, WA, USA
Neisseria Reference Laboratory, University of Washington, Seattle, WA, USA Department of Global Health, University of Washington, Seattle, WA, USA Center for AIDS and STD, University of Washington, Seattle, WA, USA.
J Antimicrob Chemother. 2014 Jun;69(6):1572-8. doi: 10.1093/jac/dkt540. Epub 2014 Jan 26.
Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. Current CDC treatment guidelines for uncomplicated gonorrhoea recommend only ceftriaxone plus either azithromycin or doxycycline. Additional treatment options are needed.
We used antibiotic gradient synergy testing (the Etest) to evaluate antimicrobial combinations that included a third-generation cephalosporin (cefixime or ceftriaxone) plus azithromycin, doxycycline, gentamicin, rifampicin or fosfomycin. We tested each combination against 28 clinical N. gonorrhoeae isolates and four control strains of varying susceptibility profiles, and compared the results with those obtained using combination antimicrobial testing using agar dilution. We calculated the fractional inhibitory concentration index (FICI) for each combination to determine synergy, the results being interpreted as follows: FICI ≤ 0.5 = synergy; FICI > 4.0 = antagonism; and FICI > 0.5-4 = indifference.
The combinations of a third-generation cephalosporin plus azithromycin, doxycycline, rifampicin, gentamicin or fosfomycin produced FICIs of indifference. The Etest and agar dilution methods produced comparable results.
Combinations of ceftriaxone plus rifampicin, gentamicin or fosfomycin may warrant further clinical investigation as treatments for gonorrhoea. Using the Etest for synergy testing is a viable method that has practical advantages over agar dilution.
耐抗菌药物的淋病奈瑟菌是主要的公共卫生威胁。美国疾病控制与预防中心（CDC）目前针对单纯性淋病的治疗指南仅推荐头孢曲松联合阿奇霉素或多西环素。因此需要其他治疗方案。
我们使用抗生素梯度协同试验（Etest）评估了包含第三代头孢菌素（头孢克肟或头孢曲松）联合阿奇霉素、多西环素、庆大霉素、利福平或磷霉素的抗菌药物组合。我们针对28株临床淋病奈瑟菌分离株和4株不同药敏谱的对照菌株测试了每种组合，并将结果与使用琼脂稀释法进行联合抗菌测试所获得的结果进行比较。我们计算了每种组合的分数抑菌浓度指数（FICI）以确定协同作用，结果解释如下：FICI≤0.5 = 协同作用；FICI>4.0 = 拮抗作用；FICI>0.5 - 4 = 无作用。
第三代头孢菌素联合阿奇霉素、多西环素、利福平、庆大霉素或磷霉素的组合产生了无作用的FICI。Etest法和琼脂稀释法产生了可比的结果。
头孢曲松联合利福平、庆大霉素或磷霉素的组合作为淋病治疗方案可能值得进一步的临床研究。使用Etest进行协同试验是一种可行的方法，与琼脂稀释法相比具有实际优势。
