Combination therapy for gonorrhoea: in vitro synergy testing

Abstract

Antimicrobial resistance in Neisseria gonorrhoeae is an increasing problem worldwide and combinations of antimicrobial agents have been recommended to delay the onset of treatment failures. The objective of this study was to obtain in vitro data on the activity of current (ceftriaxone or cefixime plus azithromycin) and alternative (gentamicin plus azithromycin) regimens. A panel of 64 gonococcal isolates displaying various cefixime MICs was selected for inclusion in the study. Determination of the activities of the antimicrobial combinations of ceftriaxone, cefixime or gentamicin with azithromycin was performed using the agar dilution method and subsequent calculation of the fractional inhibitory concentration index (FICI) values. No antagonism for any of the antimicrobial combinations was detected among the 64 gonococcal isolates. When cefixime or ceftriaxone was combined with azithromycin all isolates showed additivity/indifference with a mean FICI of 2.0. All gonococcal isolates also showed additivity/indifference with the antimicrobial combination of gentamicin with azithromycin, but with a lower mean FICI of 1.7. No significant difference in the mean FICI between isolates fully susceptible to cefixime and isolates with decreased susceptibility to cefixime was observed. The results obtained support the gonorrhoea treatment currently recommended in the UK national guidelines and suggest that gentamicin with azithromycin could be a future treatment option. The in vivo activity and efficacy of these combinations remain unknown and prospective clinical studies should be addressed.