How Do Triazaacenaphthylenes Work?

Triazaacenaphthylenes are a novel kind of antibacterial medication recently approved by the FDA to treat uncomplicated urinary tract infections in females of age 12 and above. Triazaacenaphthylenes kill bacteria (bactericidal) by blocking the activity of two bacterial enzymes that are essential for replication of the bacterial DNA.

Urinary tract infection (UTI) is one of the most common health issues in women and approximately 50% to 60% adult women are estimated to contract a urinary infection at least once in their lifetime. Several bacterial strains have also developed resistance to many of the antibiotics, making UTIs a major health problem globally.

Triazaacenaphthylenes are a new class of antibiotics used to treat UTI caused by many of the common gram-positive and gram-negative bacteria, including those that are resistant to other antibiotics. Although triazaacenaphthylenes bind to the same enzymes as fluoroquinolones, another class of antibiotics, they work differently from them.

Triazaacenaphthylenes inhibit two bacterial enzymes known as topoisomerase type II (DNA gyrase) and topoisomerase type IV, which are essential for DNA replication, survival and growth of bacteria. These enzymes cause temporary DNA breaks in order to repair, remove knots and recombine to make perfect DNA copies. Triazaacenaphthylenes prevents this, causing single-stranded DNA breaks, killing the bacteria.

Currently the first and only drug in triazaacenaphthylenes class of antibiotics is gepotidacin (Blujepa), an oral bactericidal drug approved by the FDA on March 25, 2025, to treat uncomplicated UTI caused by the following susceptible aerobic bacteria:

Gram-positive:

• Staphylococcus saprophyticus
• Enterococcus faecalis

Gram-negative:

• Escherichia coli
• Klebsiella pneumoniae
• Citrobacter freundii complex

Common side effects of triazaacenaphthylenes include the following:

• Diarrhea
• Nausea
• Abdominal pain, discomfort and tenderness
• Flatulence
• Soft stools
• Vomiting
• Headache
• Dizziness
• Vulvovaginal Candida infection (candidiasis)

Less common side effects of triazaacenaphthylenes include the following:

• Belching (eructation)
• Abdominal distension
• Indigestion (dyspepsia)
• Clostridioides difficile infection
• Excessive saliva (hypersalivation)
• Hot flush
• Heart rhythm disturbance (QTc interval prolongation)
• Rapid heart rate (tachycardia)
• Speech difficulty (dysarthria)
• Muscle spasms
• Feeling faint (presyncope)
• Fatigue
• Blurred vision
• Vertigo
• Increase in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Rash
• Excessive sweating (hyperhidrosis)
• Hypersensitivity reactions including severe allergic reactions (anaphylaxis)

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 triazaacenaphthylenes include:

• Blujepa
• gepotidacin