Antibiotic Resistance and Treatment Options for Multidrug-Resistant Gonorrhea

Gonorrhea is a sexually transmitted disease with a high global incidence. Its causative agent, Neisseria gonorrhoeae, has shown a remarkable flexibility to adapt and become resistant to all antimicrobials introduced over the past century for gonococcal therapy. The currently last available first-line therapy that is recommended in most countries is ceftriaxone. However, resistance levels against ceftriaxone are rising globally and incidences of confirmed treatment failure are increasingly encountered, particularly with the global spreading of the ceftriaxone-resistant FC428 clone in recent years. Resistance against most antimicrobials has been the result of adaptive genomic mutations that reduce affinity of the antimicrobial to its target protein or rRNA, although most multidrug-resistant strains also appear to have an upregulated multidrug efflux pump. To ensure gonococcal treatment remains available in the future, alternative therapies are urgently needed. Therefore, both alternative clinically approved antimicrobials and novel antimicrobials have been intensely studied both in gonococcal susceptibility analyses and clinical efficacy trials. Although there have been some limited successes, all studied alternative therapies that reached clinical trials have displayed some shortcomings in their efficacy against pharyngeal infections and/or overlapping resistance determinants with previously or currently used antimicrobials. This review summarizes the development of gonococcal antimicrobial resistance over the past century, describes the mechanisms involved in antimicrobial resistance, and provides an overview of the alternative therapies that have been under investigation this past decade.