Gepotidacin

Gepotidacin

• is a bacterial topoisomerase inhibitors (1)
  • a novel, first‐in‐class triazaacenaphthylene antibiotic, inhibits bacterial DNA replication by a distinct mechanism of action, conferring activity against most strains of Escherichia coli, Staphylococcus saprophyticus, and Neisseria gonorrhoeae, including those resistant to current antibiotics (1)
    
    
• in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) has approved gepotidacin as an option to treat uncomplicated urinary tract infections (UTIs) in women and girls aged 12 or older weighing at least 40 kg (2)
  • is taken as a tablet twice a day for five days
    
    
• comparative studies versus nitrofurantoin for the treatment of uncomplicated urinary tract infections (EAGLE-2 and EAGLE-3) were undertaken (3):
  • in the EAGLE-2 study, gepotidacin was shown to work at least as well as (not worse than) nitrofurantoin: 51% therapeutic success with gepotidacin, 47% with nitrofurantoin
  • in the EAGLE-3 study, the results favoured gepotidacin over nitrofurantoin:58% therapeutic success with gepotidacin, 44% with nitrofurantoin
  • from study data, the most common side effects, which may affect more than 1 in 10 people, included diarrhoea and nausea, both of which were considered mild (2)
    • in comparative studies with nitrofurantoin (3):
      • diarrhoea occurred in 14–18% of participants who took gepotidacin, and 3–4% of participants who took nitrofurantoin
      • nausea occurred in 8–11% of participants who took gepotidacin and 4% of participants who took nitrofurantoin
        
        
• although bacterial topoisomerase inhibitors (e.g. gepotidacin) bind to a similar region of the same target proteins as quinolone antibiotics, they are structurally and pharmacologically distinct from quinolones
  • gepotidacin’s novel mode of action confers activity in vitro against most strains of Escherichia coli, Staphylococcus saprophyticus, and Neisseria gonorrhoeae, including target pathogens resistant to established antibiotics, such as fluoroquinolone (1)

Reference:

1. Tiffany C et al. Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects. Clin Transl Sci. 2022 Sep;15(9):2251-2264.
2. Iacobucci G. UTIs: New antibiotic for women and girls is approved in UK. BMJ 2025; 390 :r1825
3. Wagenlehner F et al. Plain language summary: efficacy and safety of gepotidacin, a new oral antibiotic, compared with nitrofurantoin, a commonly used oral antibiotic, for treating uncomplicated urinary tract infection. Future Microbiol. 2025 Mar;20(4):265-275.