A recent Phase 3b clinical trial has demonstrated that gepotidacin (Blujepa), a new oral antibiotic, is safe and effective in rapidly improving symptoms for women with uncomplicated urinary tract infe

A new study shows oral antibiotic gepotidacin eases UTI symptoms within 24 hours, offering a vital alternative as drug resistance grows.

Studi fase 3b terbaru di JAMA Network Open melaporkan 54% perempuan dengan ISK tanpa komplikasi merasakan gejala membaik dalam 24 jam setelah gepotidacin. Namun desain studinya satu lengan, tanpa pembanding dan tanpa penyamaran. Artikel ini membedah angka, keterbatasan, keamanan, serta relevansinya bagi praktik klinis dan pengendalian resistansi antibiotik di Indonesia.

Importance  Uncomplicated urinary tract infections (uUTIs) are common infections in women, and symptoms negatively impact patients’ quality of life. Rapid symptom improvement is a high priority for patients and health care practitioners; however, few studies describe the early clinical effects of treatment.Objective  To evaluate clinical symptom improvement daily from 24 hours until end of gepotidacin treatment (96 hours) and on day 10 in females with uUTIs.Design, Setting, and Participants  This phase 3b, open-label, single-arm, multicenter nonrandomized clinical trial (October 2, 2024, to March 10, 2025) screened females (aged ≥12 years) with 2 or more uUTI symptoms and urinary nitrites or pyuria at 21 US sites.Intervention  Oral gepotidacin (1500 mg) twice daily for 5 days.Main Outcomes and Measures  The primary outcome was clinical symptom improvement (decrease in total clinical symptom score [CSS] of ≥1 from baseline without other systemic antimicrobials, with or without resolution) at 24 (±4) hours after treatment initiation. Secondary outcomes were clinical symptom improvement at 48, 72, and 96 (all ±4) hours after treatment initiation, clinical symptom resolution (reduction in total CSS to 0 without other systemic antimicrobials) at 24, 48, 72, and 96 (all ±4) hours after treatment initiation, and safety. Exploratory outcome was clinical symptom improvement and resolution at day 10 (+3 days).Results  Overall, 103 females were evaluated, with 97 enrolling, 96 completing the study, 93 completing the study treatment, and 90 (mean [SD] age, 46.1 [16.4] years) included in the clinically evaluable population for the primary outcome. At 24 hours, 49 participants (54.4%; 95% CI, 43.6%-65.0%) in the clinically evaluable population had clinical symptom improvement. The number of participants with clinical symptom improvement at 48, 72, and 96 hours was 71 of 89 (79.8%; 95% CI, 69.9%-87.6%), 81 of 90 (90.0%; 95% CI, 81.9%-95.3%), and 77 of 89 (86.5%; 95% CI, 77.6%-92.8%), respectively. Clinical symptom resolution increased from 3 of 90 patients (3.3%) at 24 hours to 81 of 90 (90.0%) at day 10. Fifty-eight adverse events, mostly mild or moderate, were reported in 27 participants from the safety population. There were no serious adverse events.Conclusions and Relevance  In this phase 3b nonrandomized clinical trial, female participants with uUTIs experienced a rapid clinical response to gepotidacin as early as 24 hours after treatment initiation. These data may aid informed decision-making in the use of gepotidacin for treating uUTIs.Trial Registration  ClinicalTrials.gov Identifier: NCT06597344

This nonrandomized clinical trial investigates clinical symptom response during treatment with gepotidacin among females with clinically diagnosed uncomplicated urinary tract infections to assess how ...

More than half the women in the small, single-arm trial experienced symptom relief in 24 hours.

More than half the women in the small, single-arm trial experienced symptom relief in 24 hours.

Gepotidacin demonstrated non-inferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital...

and objectivesEffective therapies for the treatment of uncomplicated urinary tract infections (uUTIs) are increasingly limited due to rising multidrug resistance, necessitating the development of novel antimicrobials. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA gyrase and topoisomerase IV through a distinct binding site, a unique mechanism of action, and with well-balanced inhibition for most pathogens. Gepotidacin was recently approved by the FDA and MHRA for the treatment of uUTIs and by the FDA for uncomplicated urogenital gonorrhoea. This study investigated the development of resistance to gepotidacin among isolates from two Phase 3 uUTI clinical trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]).MethodsPost-baseline isolates exhibiting a reproducible ≥4-fold increase in minimum inhibitory concentration (MIC) and non-distinct multi-locus sequence typing/pulsed-field gel electrophoresis results underwent single nucleotide polymorphism/insertion-deletion analysis.ResultsAcross both studies, initial MIC testing showed 58/1045 (5.6%) patients with pathogen(s) demonstrating an apparent ≥4-fold increase in post-baseline gepotidacin MIC. Analyses identified only one patient with multiple Escherichia coli isolate pairs displaying potential development of resistance to gepotidacin. While the post-baseline isolates did not meet the putative direct descendancy criteria, we have conservatively considered this a case of possible development of resistance due to the rarity of the gepotidacin target-specific mutation (ParC D79G) in the on-therapy and test-of-cure E. coli isolates.ConclusionsCollectively, results from the Phase 3 trials indicate a low incidence of resistance development to gepotidacin, with only one potential case among gepotidacin-treated patients (1/1045; 0.096%). Further research is warranted to elucidate the mechanisms underlying elevated post-baseline gepotidacin MICs.

Learn more about zoliflodacin and gepotidacin cross-resistance and fitness in N. gonorrhoeae, the benefits of rifapentine- and rifabutin-based regimens for tuberculosis meningitis and other research ready to inform clinical practice.

Oral gepotidacin yields NAAT-based success rates comparable with ceftriaxone plus azithromycin in uncomplicated urogenital gonorrhea.

Oral gepotidacin yields NAAT-based success rates comparable with ceftriaxone plus azithromycin in uncomplicated urogenital gonorrhea.

The emergence of multidrug-resistant Neisseria gonorrhoeae has created an urgent need for new therapeutic options. Zoliflodacin and gepotidacin, 2 first-in-class topoisomerase inhibitors, are oral antibiotics recently approved by the FDA for gonorrhea treatment. Resistance to zoliflodacin can occur through gyrBD429N, but this mutation's impact on fitness and on resistance to other topoisomerase-targeting drugs have been unclear. The aim of this study was to investigate the in vitro fitness and antibiotic resistance implications of gyrBD429N in ciprofloxacin-resistant N. gonorrhoeae strains.MethodsWe introduced the gyrBD429N substitution into 9 clinical strains via transformation. Antimicrobial susceptibility testing was performed for zoliflodacin, gepotidacin, and ciprofloxacin using standard MIC assays. In vitro relative fitness of parent and resistant mutant strains was assessed by pairwise competition experiments.ResultsgyrBD429N conferred cross-resistance to gepotidacin in 3 clinical strains, and its fitness effect varied by strain background. In particular, parCD86N appeared to potentiate gyrBD429N cross-resistance to gepotidacin, a drug for which resistance has previously only been seen in the presence of both parCD86N and gyrAA92T mutations.ConclusionsGenetic background modulated the phenotypic effects of a zoliflodacin-resistance determinant on fitness and cross-resistance to gepotidacin. These findings inform strategies for introducing the new topoisomerase inhibitors into clinical use and for surveillance of resistance.

The phase 3 EAGLE-1 trial demonstrated noninferiority of oral gepotidacin to ceftriaxone plus azithromycin for treating uncomplicated urogenital gonorrhea. To reflect real-world practice, we conducted an exploratory analysis of efficacy assessed by nucleic acid amplification tests (NAAT).MethodsEAGLE-1 (NCT04010539) compared the efficacy and safety of oral gepotidacin (2 × 3000 mg) with intramuscular ceftriaxone (1 × 500 mg) plus oral azithromycin (1 × 1000 mg) in participants (≥12 years) with uncomplicated urogenital gonorrhea. Urogenital specimens for NAAT were collected at baseline and test-of-cure (days 4–8). The microbiological intent-to-treat (micro-ITT) population comprised all participants who received ≥1 dose of study treatment, with culture-confirmed ceftriaxone-susceptible urogenital Neisseria gonorrhoeae at baseline. The microbiologically evaluable NAAT test-of-cure population comprised micro-ITT participants with valid baseline NAAT-positive results, who followed important trial protocol components and valid test-of-cure NAAT results. NAAT–confirmed treatment success was defined as nucleic acid clearance at the test-of-cure.ResultsHigh concordance between NAAT and culture results was observed (98.4%). In the micro-ITT population, NAAT-confirmed success rates at the test-of-cure were 82.5% (151/183) for gepotidacin and 75.0% (132/176) for ceftriaxone plus azithromycin (adjusted difference 8.2%, 95% confidence interval [CI], −0.1%, 16.5%); numerically lower than the corresponding culture-confirmed success rates of 92.6% (187/202) and 91.2% (186/204). In the microbiologically evaluable NAAT test-of-cure population, NAAT-confirmed success rates at the test-of-cure were 88.3% (151/171) for gepotidacin and 86.3% (132/153) for ceftriaxone plus azithromycin (adjusted difference 3.8%, 95% CI, −3.6%, 11.2%).ConclusionsThe NAAT-confirmed success rates were high and similar between treatments, supporting the primary analysis results based on culture.