Combatting antimicrobial-resistant Neisseria gonorrhoeae: new antibiotics and the pipeline of antigonococcal therapeutics.

PURPOSE OF REVIEW: Gonorrhea is the second most prevalent bacterial sexually transmitted infection globally. The proliferation of antimicrobial-resistant strains has severely limited treatment options. New treatment modalities against multidrug-resistant gonococcal infections to reduce the rate of transmission and the risk of complications are urgently needed. This review summarizes ongoing efforts in the development of new antibiotics and alternative treatment approaches, including repurposing drugs, biologics, and small molecules.

RECENT FINDINGS: Gepotidacin and zoliflodacin are topoisomerase inhibitors that have shown promise in phase 3 clinical trials and are pending FDA approval for the treatment of uncomplicated gonorrhea. These drugs are active against currently circulating multidrug-resistant isolates and provide much-needed oral treatment options. Monoclonal antibodies have increasingly been deployed for treating infections. The identification of bactericidal human monoclonal antibodies with efficacy in preclinical animal models provides optimism for their development as passive immunoprophylactics. Several small molecules with activity against Neisseria gonorrhoeae have been identified; the identification of drugs using artificial intelligence is a particularly exciting advance.

SUMMARY: Recent advances in the development of antibiotics, biologics and small molecules against gonorrhea provide optimism against the stark background of multidrug-resistant gonorrhea. Ongoing surveillance remains critical to evaluate the efficacy of newly introduced treatments.