Will use of combination cephalosporin/azithromycin therapy forestall resistance to cephalosporins inNeisseria gonorrhoeae?

The history of antimicrobial therapy of Neisseria gonorrhoeae infections has been one of recurrent development of resistance towards the antibiotics recommended as first-line therapies.1 ,2 The initial discovery of penicillin was lifesaving for those who suffered from serious staphylococcal and streptococcal infections, but also provided the first truly effective therapy against disseminated gonococccal infections. The emergence of gonococcal penicillin resistance associated with increasing clinical use of penicillin to treat gonococcal infections led to more use of tetracycline for treatment, which was associated with the emergence and spread of tetracycline resistance. Similarly for the use of spectinomycin. Once prevalent, resistance determinants persist even when use of the associated antibiotic declines, and re-emerge rapidly on reintroduction of the antibiotic. Early use of ceftriaxone was not associated with emergence of resistance, but its widespread use diminished with the introduction of oral cephalosporins such as cefixime and the clinical availability of the fluoroquinolones. Unfortunately, substantial resistance emerged to both fluoroquinolones and oral cephalosporins, resulting in a return of ceftriaxone as recommended first-line therapy for gonococcal infections. With the recent widespread use of ceftriaxone for first-line therapy, we are now observing the emergence of gonococcal strains resistant to this agent.3 As there are no other drugs predictably effective as single doses for resistant strains, we face the prospect of worldwide spread of untreatable gonorrhoea. The exodus of many large pharmaceutical firms from the antibacterial therapeutic area in recent decades has heightened the urgency of the gonococcal resistance problem.4 Put simply, there are a few drugs in the pipeline likely to be effective in single doses against multiresistant gonococcal strains. As such, there is increasing interest in strategies to forestall the spread of gonococcal ceftriaxone resistance. Common strategies to forestall resistance, such as withholding antibiotics pending culture confirmation of infection, are impractical …