Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India.
J Med Microbiol. 2019 Apr;68(4):555-559. doi: 10.1099/jmm.0.000953. Epub 2019 Mar 14.
The public health burden of infections caused by Neisseria gonorrhoeae is magnified due to high rates of resistance to traditional antimicrobials. The aim of this study was to evaluate the in vitro efficacy of an alternative dual therapy comprising gentamicin and azithromycin.
The E-test method was used to determine the minimum inhibitory concentrations (MICs) of gentamicin and azithromycin individually prior to testing in combination using the cross or 90 angle formation method. A total of 70 clinical isolates of N.gonorrhoeae displaying varying ceftriaxone MICs along with 2 reference strains (WHO K and P) and 1 ceftriaxone-resistant QA isolate were examined. The fractional inhibitory concentration index (FICI) was calculated and the results were interpreted using the following criteria: synergy, FICI ≤0.5; indifference or additive, FICI >0.5 to ≤4.0; and antagonism, FICI >4.0.
A total of 54 (77.1 %) isolates displayed indifference, while 16 (22.9 %) demonstrated synergy. When azithromycin was tested alone, the MICs ranged from 0.016 to 2 µg ml . However, in combination with gentamicin, the mean MIC value of all isolates decreased from 0.275 µg ml to 0.090 µg ml (P=0.05).When gentamicin was tested alone, the MICs ranged from 0.25 to 8 µg ml, with a mean MIC of 4.342 µg ml, whereas in combination with azithromycin it decreased significantly to 2.042 µg ml (P=0.04).
No antagonism was observed in this combination, suggesting that it could be a future treatment option as we prepare for a post-cephalosporin era. However, comprehensive in vivo evaluations are warranted and recommendations should be made based on clinical trials.
由于传统抗生素的耐药率较高,淋病奈瑟菌引起的感染对公共卫生的负担加重。本研究旨在评估包含庆大霉素和阿奇霉素的替代双联疗法的体外疗效。
使用 E 试验法分别测定庆大霉素和阿奇霉素的最低抑菌浓度(MIC),然后采用交叉或 90 度角形成法联合检测。共检测了 70 株具有不同头孢曲松 MIC 的淋病奈瑟菌临床分离株,以及 2 株参考株(世界卫生组织 K 和 P 株)和 1 株头孢曲松耐药 QA 分离株。计算部分抑菌浓度指数(FICI),并根据以下标准解释结果:协同作用,FICI≤0.5;无关或相加作用,FICI>0.5 至≤4.0;拮抗作用,FICI>4.0。
共有 54 株(77.1%)分离株表现为无关,16 株(22.9%)表现为协同。单独检测阿奇霉素时,MIC 范围为 0.016 至 2μg/ml。然而,与庆大霉素联合使用时,所有分离株的平均 MIC 值从 0.275μg/ml 降低至 0.090μg/ml(P=0.05)。单独检测庆大霉素时,MIC 范围为 0.25 至 8μg/ml,平均 MIC 为 4.342μg/ml,与阿奇霉素联合使用时显著降低至 2.042μg/ml(P=0.04)。
在该联合用药中未观察到拮抗作用,这表明它可能是我们为头孢菌素后时代做准备的未来治疗选择。然而,需要进行全面的体内评估,并根据临床试验提出建议。