Development of New Antimicrobials for Urogenital Gonorrhea Therapy: Clinical Trial Design Considerations.

Abstract

Gonorrhea remains a major public health challenge and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetics/pharmacodynamics contributors to effective therapy and to prevention of antimicrobial resistance, to newer designs for Phase -2 and -3 clinical trials, and is hampered by the requirement to utilize currently recommended combination ceftriaxone/azithromycin therapy as the comparator regimen in non-inferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints likewise hinder enrollment of populations at greatest risk for gonorrhea (adolescents, women, persons infected with antibiotic resistant Neisseria gonorrhoeae). This Viewpoint summarizes a recent meeting to re-consider the evaluation process for antimicrobials for urogenital gonorrhea treatment and highlights these themes to encourage consideration of new designs for evaluation of gonorrhea therapy.