In vitro assessment of gentamicin and azithromycin-based combination therapy against Neisseria gonorrhoeae isolates in India

Purpose. 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. Methodology. 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 90o 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. Results. 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−1 . However, in combination with gentamicin, the mean MIC value of all isolates decreased from 0.275 µg ml−1 to 0.090 µg ml−1 (P=0.05).When gentamicin was tested alone, the MICs ranged from 0.25 to 8 µg ml−1, with a mean MIC of 4.342 µg ml−1, whereas in combination with azithromycin it decreased significantly to 2.042 µg ml−1 (P=0.04). Conclusion. 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.