Background Antimicrobial resistance in Neisseria gonorrhoeae is a major public health problem worldwide. Recently, the first gonococcal isolates with high-level resistance to extended-spectrum cephalosporins, including ceftriaxone, were reported and gonorrhoea may become untreatable in certain circumstances. As a response, dual antimicrobial therapy (mainly ceftriaxone+azithromycin) has been introduced in the USA and Europe. The aim of this study was to apply a method for in vitro synergy testing, using Etest methodology, of various combinations of antimicrobials, i.e. currently used or of potential interest for future dual antimicrobial therapy.

Methods The eight WHO 2008 N. gonorrhoeae reference strains and 51 clinical N. gonorrhoeae isolates were investigated by synergy testing using Etest of in total 15 combinations of ceftriaxone, cefixime, azithromycin, moxifloxacin, spectinomycin, and gentamicin.

Results Highest levels of synergistic and/or additive effects, without any observed antagonistic effects, were observed for the combinations cefixime+gentamicin (in total 80% of isolates), azithromycin+gentamicin (65%), and cefixime+azithromycin (63%). The combination of ceftriaxone+azithromycin, currently recommended in the dual antimicrobial therapy, also showed substantial synergistic and/or additive effects (34%), without any observed antagonistic effects. Nevertheless, the results of in vitro antimicrobial synergy testing need to be interpreted with some caution, because these may not absolutely correspond to the in vivo situation.

Conclusion This study demonstrates in vitro synergy between several of the antimicrobials currently used or potentially considered for dual antimicrobial therapy of gonorrhoea and this is also the first study using Etest as an objective, easily performed and reproducible in vitro method for dual antimicrobial synergy testing of N. gonorrhoeae. Such method might be crucial if susceptibility testing for combination antimicrobial therapy will be performed prior to treatment of gonorrhoea.