Sex Transm Dis. 2018 Feb;45(2):127-131. doi: 10.1097/OLQ.0000000000000708.
Emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Neisseria gonorrhoeae is a serious concern and combination therapy has been recommended to delay the onset of treatment failures. Gentamicin, an old and inexpensive antibiotic, is recommended in combination with azithromycin for treatment failures cases with the first-line regimen as per the latest Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines. However, not much literature is available on in vitro and in vivo efficacy of this combination. Therefore, this study was carried out to evaluate the in vitro synergy of gentamicin in combination with azithromycin and 5 other antimicrobials.
In vitro synergy of gentamicin in combination with cefixime, ceftriaxone, spectinomycin, azithromycin, moxifloxacin, and ertapenem was determined by Etest for 75 N. gonorrhoeae strains, of which 65 were MDR and one was XDR. Fractional inhibitory concentration index (FICI) of ≤0.5 and >4.0 denoted synergy and antagonism respectively.
Maximum efficacy of gentamicin was observed in combination with ertapenem (geometric mean FICI, 0.56) followed by cefixime (FICI, 0.87). There was no antagonism for both these combinations. However, antagonism was demonstrated in 5.3%, 8%, 8%, and 10.7% strains when gentamicin was paired with spectinomycin (FICI, 1.34), ceftriaxone (FICI, 1.13), azithromycin (FICI, 1.49), and moxifloxacin (FICI, 1.30), respectively.
The findings suggest that gentamicin significantly enhances the in vitro therapeutic potency of ertapenem and cefixime which will be potentially effective to control the spread of MDR and XDR N. gonorrhoeae. The study warrants more in vitro studies and clinical trials for gentamicin + azithromycin and other 3 combinations because of considerable antagonism.
耐多药(MDR)和广泛耐药(XDR)淋病奈瑟菌的出现令人严重关切,推荐联合治疗以延缓治疗失败的发生。庆大霉素是一种古老且廉价的抗生素,根据疾病控制与预防中心最新的性传播疾病治疗指南,被推荐与阿奇霉素联合用于治疗一线方案治疗失败的病例。然而,关于这种联合治疗的体外和体内疗效的文献并不多。因此,进行这项研究是为了评估庆大霉素与阿奇霉素和其他 5 种抗菌药物联合使用的体外协同作用。
用 Etest 测定 75 株淋病奈瑟菌(其中 65 株为 MDR,1 株为 XDR)中庆大霉素与头孢克肟、头孢曲松、壮观霉素、阿奇霉素、莫西沙星和厄他培南联合使用的体外协同作用。FICI 值≤0.5 和>4.0 分别表示协同作用和拮抗作用。
庆大霉素与厄他培南(几何平均 FICI 为 0.56)联合使用效果最佳,其次是与头孢克肟(FICI 为 0.87)联合使用。这两种组合均无拮抗作用。然而,当庆大霉素与壮观霉素(FICI 为 1.34)、头孢曲松(FICI 为 1.13)、阿奇霉素(FICI 为 1.49)和莫西沙星(FICI 为 1.30)联合使用时,分别有 5.3%、8%、8%和 10.7%的菌株表现出拮抗作用。
这些发现表明,庆大霉素显著增强了厄他培南和头孢克肟的体外治疗效果,这可能有助于控制 MDR 和 XDR 淋病奈瑟菌的传播。鉴于存在相当大的拮抗作用,该研究需要更多的体外研究和临床试验来验证庆大霉素+阿奇霉素以及其他 3 种组合的疗效。