Background Genital tract infections caused by Neisseria gonorrhoeae are a major cause of sexually transmitted disease worldwide. Surveillance data suggest that incidence has increased in recent years after initially falling in the face of intensified control efforts.

Objectives The authors sought to evaluate the potential contribution of antimicrobial resistance to such rebound and to identify optimal treatment strategies in the face of resistance using a mathematical model of gonorrhoea.

Methods The authors built risk-structured ‘susceptible–infectious–susceptible’ models with and without the possibility of antibiotic resistance and used these models as a platform for the evaluation of competing plausible treatment strategies, including changing antimicrobial choice when resistance prevalence surpassed fixed thresholds, random assignment of treatment and use of combination antimicrobial therapy.

Results Absent antimicrobial resistance, strategies that focus on treatment of highest risk individuals (the so-called core group) result in collapse of disease transmission. When antimicrobial resistance exists, a focus on the core group causes rebound in incidence, with maximal dissemination of antibiotic resistance. Random assignment of antimicrobial treatment class outperformed the use of fixed resistance thresholds with respect to sustained reduction in gonorrhoea prevalence.

Conclusions Gonorrhoea control is achievable only when core groups are treated, but treatment of core groups maximises dissemination of antimicrobial-resistant strains. This paradox poses a great dilemma to the control and prevention of gonorrhoea and underlines the need for gonococcal vaccines.