HOW DO SPIROPYRIMIDINETRIONES WORK?

Spiropyrimidinetriones are a novel class of antibacterial agents developed to treat uncomplicated gonorrhea caused by drug-resistant Neisseria gonorrhoeae. This drug class is distinguished by a unique chemical structure and a mechanism of action that differs from established antibiotic classes such as fluoroquinolones, macrolides, and β-lactams.

Spiropyrimidinetriones exert their antibacterial effect by inhibiting bacterial DNA gyrase, a type II topoisomerase essential for DNA replication, transcription, and cell division. These agents bind to the DNA-gyrase cleavage complex and prevent re-ligation of DNA strands, leading to disruption of DNA synthesis and inhibition of bacterial replication. Their binding site and mechanism are distinct from those of fluoroquinolones and ATP-competitive GyrB inhibitors, reducing the likelihood of cross-resistance.

Zoliflodacin is the first-in-class spiropyrimidinetrione antibiotic. In December 2025, the FDA approved zoliflodacin for the treatment of uncomplicated urogenital gonorrhea in adults and adolescents, representing an important advance in the management of multidrug-resistant N. gonorrhoeae.

Spiropyrimidinetriones are administered orally for the treatment of uncomplicated gonorrhea in adults and pediatric patients 12 years of age and older who weigh at least 35 kg. Zoliflodacin is supplied as granules in a single-dose packet that must be mixed with water prior to administration and should not be combined with other liquids or food. The recommended dose is 3 g (one packet) administered as a single oral dose.

Common side effects of spiropyrimidinetriones include the following:

• Headache
• Dizziness
• Nausea
• Diarrhea
• Neutropenia
• Leukopenia

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of FDA-approved spiropyrimidinetriones include:

• Nuzolvence
• zoliflodacin