Journal of Paramedical Sciences & Rehabilitation

Journal of Paramedical Sciences & Rehabilitation

A New Antibiotic for Treatment of Urinary Tract Infection -A Review Study

Document Type : Review Article

Authors
M Arefnezhad 1
E Mohammadzadeh 1
F Shad 1
F Jafarian 1
M Arefnezhad 2
1 Department of Medical Laboratory Sciences, Kashmar School of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Laboratory Sciences, Faculty of Science, Islamic Azad University of Mashhad, Mashhad, Iran
10.22038/jpsr.2025.84590.2673
Abstract
Purpose: One of the significant challenges in treating urinary tract infection (UTL) is emergence of antibiotic resistance bacteria. Gepotidacin, a new antibiotic, has been designed to combat bacterial infection, practically UTIs, and may serve as a traditional antibiotic. The present review study aims to investigate the efficacy and safely of Gepotidacin in treating UTIs, practically those caused by antibiotic resistant bacteria.
Methods: A comprehensive search of PubMed and Google Scholar databases was conducted to identify relevant studies published between 2010 - 2024. The search keywords included urinary tract infection, Gepotidacin and antibiotic resistance.
Results: Gepotidacin has demonstrated potent antibacterial activity against range of pathogens, including Gram-positive and Gram-negative bacteria, practically those resistant to Fluoroquinolones and other antibiotics. Minimums inhibitory concentrations (MIC) of Gepotidacin was found to be lower than that of other antibiotics, including its potential as a more effective treatment option.
Conclusion: Gepotidacin is a promising antibiotic that may provide a solution to growing problems on antibiotic resistance in UTIs. Its unique mechanisms of action, which targets the DNA gyrase and topoisomerase IV enzymes, makes it an attractive alternative to traditional antibiotics.  Further studies are needed to fully explore the potential of Gepotidacin in clinical practice.
Keywords
Urinary Tract Infection
Gepotidacin
Antibiotic Resistance
Antibiotic Therapy
  1. Wagenlehner F, Perry CR, Hooton TM, Scangarella-Oman NE, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet 2024; 403(10428): 741-755.
  2. Anderson GG, Goller CC, Justice S, Hultgren SJ, Seed PC. Polysaccharide capsule and sialic acidmediated regulation promote biofilm -like intracellular bacterial communities during cystitis. Infect Immun 2010; 78(3): 963 -975.
  3. Watkins RR, Dipendra Thapaliya D, Lemonovich TL, Bonomo RA. Gepotidacin: a novel, oral, ‘first-in-class’ triazaacenaphthylene antibiotic for the treatment of uncomplicated urinary tract infections and urogenital gonorrhea. J Antimicrob Chemother 2023; 78(5): 1137-1142.
  4. Genovese C, Davinelli S, Mangano K, Tempera G, et al. Effects of a new combination of plant extracts plus d -mannose for the management of uncomplicated recurrent urinary tract infections. J Chemother 2018; 30(2): 107-114.
  5. Jakielaszek C, Hilliard JJ, Mannino F, Hossain M, et al. Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge. Antibacrob Agents Chemother 2023; 67(5): e0138122.
  6. Sebastian Walesch S, Joy Birkelbach J, Jezequel GFP, Jake Haeckl FP, et al. Fighting antibiotic resistance—strategies and (pre)clinical developments to find new Antibacterials. EMBO Rep 2023; 24(1): e56033.
  7. Mousavi SMM, Tazari F. Evaluating the prevalence antibiotic resistance pattern of bacteria isolated from urinary tract infection in Savadkuh city from the beginning of April 2020 to the end of September 2020. NCMBJ 2022; 12(46): 55-64.
  8. Koeth LM, DiFranco-Fisher JM, Scangarella-Oman NE. Analysis of the effect of urine on the in vitro activity of gepotidacin and levofloxacin against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus. Diagn Microbiol Infect Dis 2023; 106(3): 115946.
  9. Farrell DJ,  Sader HS,  Rhomberg PR,  Scangarella-Oman NE, Flamm R. In vitro activity of gepotidacin (GSK2140944) against Neisseria gonorrhoeae. Antimicrob Agents Chemother 2017; 61(3): e02047-16.
  10. Bax BD, Chan PF, Eggleston DS, Fosberry A, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 2010; 466:935-940.
  11. Flamm RK, Farrell DJ, Rhomberg PR, Scangarella-Oman NE, Sader HS. Gepotidacin (GSK2140944), In Vitro Activity against Gram-Positive and Gram-Negative Bacteria. Antimicrob Agents Chemother 2017; 61(7): e00468-17.
  12. Trautner BW,  Kaye KS, Gupta V,  Mulgirigama A, et al. Risk Factors Associated With Antimicrobial Resistance and Adverse Short-Term Health Outcomes Among Adult and Adolescent Female Outpatients With Uncomplicated Urinary Tract Infection. Open Forum Infect Dis 2022; 9(120): ofac623.
  13. Barth A, Hossain M, Brimhall DB, Perry CR, et al. Pharmacokinetics of oral formulations of gepotidacin (GSK2140944), a triazaacenaphthylene bacterial type II topoisomerase inhibitor, in healthy adult and adolescent participants. Antimicrob Agents Chemother 2022; 66(1): e0126321
  14. Chanbari. M, Mirnejad R, Babapour E. Evaluation of Resistance to Fluoroquinolones and its Relationship whit parC Gene mutation in Klebsiella pneumoniae Clinical Isolates. Iran J Med Microbiol 2020; 14(3): 270-289.
  15. Rich SN, Klann EM, Almond CR, Larkin EM, et al. Associations between antibiotic prescriptions and recurrent urinary tract infections in female college students. Epidemiol Infect 2019; 147: e119.
  16. Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol 2019; 11: 175628721983217.
  17. Kaye KS, Gupta V, Mulgirigama A, Joshi AV, et al. Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: rising ESBL strains and impact on patient management. Clin Infect Dis 2021; 73(11): 1992-1999.
  18. O’Riordan W, Tiffany C, Scangarella-Oman N, Perry C, et al. Efficacy, safety, and tolerability of gepotidacin (GSK2140944) in the treatment of patients with suspected or confirmed Gram-positive acute bacterial skin and skin structure infections. Antimicrob Agents chemother 2017;61(6): e02095-16.
  19. Gibson EG, Bax B, Chan PF, Osheroff N. Mechanistic and structural basis for the actions of the antibacterial gepotidacin against Staphylococcus aureus gyrase. ACS Infect Dis 2019; 5(4):570-581.
  20. Rozwadowski M, Gawel D. Molecular factors and mechanisms driving multidrug resistance in uropathogenic Escherichia coli–an update. Genes (Basel) 2022; 13(8): 1397.
  21. Watkins RR. Antibiotic stewardship in the era of precision medicine. JAC Antimicrob Resist 2022; 4(3): dlac066.
  22. Bouchillon S, Hackel M, Miller LA, Scangarella-Oman NE. In vitro activity of GSK2140944, a novel topoisomerase inhibitor, against isolates associated with lower respiratory tract and skin infections. Fifty-Third Inter science Conference on Antimicrobial Agents and Chemotherapy, Denver, CO, USA, 2013. Abstract F-1216.
  23. Kresken M,  Wohlfarth E,  Weikel C,  Butler D,  et al. In vitro activity of gepotidacin against urine isolates of Escherichia coli from outpatient departments in Germany. J Antimicrob Chemother 2023; 78: 418-22.
  24. Biedenbach DJ, Bouchillon SK, Hackel M, Miller LA, et al. In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens. Antimicrobe Agents Chemotherapy 2016; 60(3): 1918-1923.
  25. Tiffany CA, Hossain M, McDonald M, Patel A, et al. Safety and pharmacokinetics of single escalating oral doses of GSK2140944, a novel bacterial topoisomerase inhibitor, abstr F-1216. Abstr 53rd Intersci Conf. Antimicrob Agents Chemother 2013.
  26. Ryan Arends SJ, Butler D, Scangarella-Oman N, Castanheira M, Mendes RE. Antimicrobial Activity of Gepotidacin Tested against Escherichia coli and Staphylococcus saprophyticus Isolates Causing Urinary Tract Infections in Medical Centers Worldwide (2019 to 2020). Antimicrobial Agents and Chemotherapy 2023; 67(4): e0152522
  27. Scangarella-Oman NE, Dixon P, Koeth LM, DiFranco-Fisher J, Miller LA. Analysis of antimicrobial susceptibility testing methods and variables and in vitro activity of gepotidacin against urogenital Neisseria gonorrhoeae in men. Diagn Microbiol Infect Dis 2021; 101(4): 115484.
  28. Hackel MA, Karlowsky JA, Canino MA, Sahm DF, Scangarella- Oman NE. In vitro activity of gepotidacin against Gram-negative and Gram-positive anaerobes. Antimicrob Agents Chemother 2022; 66(2): e0216521.
  29. Oviatt AA., Gibson EG., Huang J, Mattern K, et al. Interactions between Gepotidacin and Escherichia coli Gyrase and Topoisomerase IV: Genetic and Biochemical Evidence for Well-Balanced Dual-Targeting. ACS Infect Dis 2024, 10(4): 1137-1151.
  30. Martins JLR, Pinto EMH, Oliveira SA, Gomes FAC, Silva ON. Treatment of Sexually Transmitted Infections (STIs) Caused by Neisseria gonorrhoeae and the Global Shortage of Antibiotics. Venereology 2022, 1(3): 235–244.
  31. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. https://www.cdc.gov/drugresistance/ pdf/ threats-report/2019-ar-threats-report-508.
  32. Walensky RP, Houry DD, Jernigan DB, Bunnell R, et al. Sexually transmitted infections treatment guidelines, MMWR Recomm Rep 2021; 70(4): 1-187. 
  33. Taylor SN, Morris DH, Avery AK, Workowski KA, et al. Gepotidacin for the treatment of uncomplicated urogenital gonorrhea: a phase 2, randomized, dose-ranging, single-oral dose evaluation. Clin Infect Dis 2018; 67(4): 504-512.
  34. Golparian D, Kittiyaowamarn R, Paopang P, Sangprasert P, et al. Genomic surveillance and antimicrobial resistance in Neisseria gonorrhoeae isolates in Bangkok, Thailand in 2018. J Antimicrob Chemother 2022; 77(8): 2171-2182.
  35. Naiyaz AM, Garg T, Singh S, Shukla R, et al. In Vitro and In Vivo Activity of Gepotidacin against Drug-Resistant Mycobacterial Infections. Antimicrob Agents Chemother 2022; 66(12): e0056422.
  36. Jensen JS, Nørgaard C, Scangarella-Oman N, Unem M. In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and-susceptible Mycoplasma genitalium. Emerg Microbes Infect 2020; 9(1): 1388-1392.
Journal of Paramedical Sciences & Rehabilitation
Volume 13, Issue 4
Winter 2025
Pages 75-84