• The use of oral fosfomycin-trometamol in modern clinical practice
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The use of oral fosfomycin-trometamol in modern clinical practice

Ukrainian Journal of Perinatology and Pediatrics. 2020. 1(81): 94-101; doi 10.15574/PP.2020.81.94
I.G. Bereznyakov
Kharkiv Medical Academy of Postgraduate Education, Ukraine

For citation: Bereznyakov IG. (2020). The use of oral fosfomycin-trometamol in modern clinical practice. Ukrainian Journal of Perinatology and Pediatrics. 1(81): 94-101. doi 10.15574/PP.2020.81.94
Article received: Jan 04, 2020. Accepted for publication: Mar 18, 2020.

The aim is to analyze the use of fosfomycin-trometamol (FT) in the treatment of acute lower uncomplicated urinary tract infections.
The analysis of data in literature was performed regarding: FT antibacterial activity spectrum; immunomodulatory properties of the drug and its action on biofilms; pharmacokinetics of FT after oral administration; results of microbiological tests of pathogens sensitivity to FT in urinary tract infections; sensitivity of multiresistant strains of bacteria to the drug; results of clinical trials of FT in patients with acute cystitis; drug safety; fosfomycin in current international and national guidelines for the treatment of acute uncomplicated cystitis; FT on the Ukrainian market. Fosfomycin-trometamol is the bactericidal antibiotic of choice in the treatment of acute lower uncomplicated urinary tract infections and, at the same time, is the only one with the course dose to be taken once. A unique mechanism of action, with inhibition of the outer membranes synthesis of bacterial cells at an early stage, results in extremely rare occurrence of co-resistance to antibiotics of other classes in pathogens. The results of clinical and microbiological studies indicate high efficiency of FT in acute uncomplicated cystitis, including cases caused by «problematic» multiresistant strains. FT tolerance is comparable to that of comparison drugs in non-pregnant women and is better in pregnant women. Fosfomed and some other generic FT drugs are available on the Ukrainian market.
No conflict of interest were declared by the author.
Key words: fosfomycin-trometamol, lower urinary tract infections, pregnancy.

REFERENСES

1. Bardova KO. (2020). Deiaki aspekty zastosuvannia fosfomitsynu v likuvanni postkoitalnoho tsystytu v praktytsi dermatoveneroloha. Ukrainskyi zhurnal dermatolohii, venerolohii, kosmetolohii. 1 (76): 93–98.

2. Aghamali M, Sedighi M, Zahedi bialvaei A et al. (2019). Fosfomycin: mechanisms and the increasing prevalence of resistance. J Med Microbiol. 68: 11–25. https://doi.org/10.1099/jmm.0.000874; PMid:30431421

3. Alfaresi M, Hassan K, Alnjadat RMH. (2019). Single-dose fosfomycin trometamol versus other antimicrobial regimens for treatment of uncomplicated lower urinary tract infection: a systematic review and meta-analysis. Open Microbiol J. 13: 193–199. https://doi.org/10.2174/1874285801913010193

4. Bergan T, Thorsteinsson SB, Albini E. (1993). Pharmacokinetic profile of fosfomycin trometamol. Chemotherapy. 39: 297–301. https://doi.org/10.1159/000239140; PMid:8370321

5. Bergan T. (1990). Degree of absorption, pharmacokinetics of fosfomycin trometamol and duration of urinary antibacterial activity. Infection. 18 (2): S65–S69. https://doi.org/10.1007/BF01643430; PMid:2286464

6. Borsa F, Leroy A, Fillastre JP et al. (1988). Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults. Antimicrob. Agents Chemother. 32: 938–941. https://doi.org/10.1128/AAC.32.6.938; PMid:3415215 PMCid:PMC172313

7. Candel FJ, David MM, Lopez JB. (2019). New perspectives for reassessing fosfomycin: applicability in current clinical practice. Rev Esp Quimioter. 32 (1): 01–07.

8. Carlone NA, Borsotto M, Cuffini AM et al. (1987). Effect of fosfomycin trometamol on bacterial adhesion in comparison with other chemotherapeutic agents. Eur. Urol. 13 (1): S86-S91. https://doi.org/10.1159/000472869; PMid:3552703

9. Christensen BG, Leanza WJ, Beattie TR et al. (1969). Phosphonomycin: structure and synthesis. Science. 166: 123–125. https://doi.org/10.1126/science.166.3901.123; PMid:5821213

10. De Cueto M, Aliaga L, Alуs JI et al. (2017). Executive summary of the diagnosis and treatment of urinary tract infection: guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC). Enferm Infecc Microbiol Clin. 35 (5): 314–320. https://doi.org/10.1016/j.eimc.2016.11.005; PMid:28017477

11. EAU Guidelines. (2018). Edn. presented at the EAU Annual Congress Copenhagen. ISBN 978–94-92671-01-1.

12. Eschenburg S, Priestman M, Schonbrunn E. (2005). Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol. Chem. 280: 3757–3763. https://doi.org/10.1074/jbc.M411325200; PMid:15531591

13. Falagas ME, Kastoris AC, Kapaskelis AM et al. (2010). Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 10: 43–50. https://doi.org/10.1016/S1473-3099(09)70325-1

14. Falagas ME, Maraki S, Karageorgopoulos DE et al. (2010). Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin. Int. J Antimicrob. Agents. 35: 240–243. https://doi.org/10.1016/j.ijantimicag.2009.10.019; PMid:20034765

15. Falagas ME, Vouloumanou EK, Samonis G et al. (2016). Fosfomycin. Clin. Microbiol. Rev. 29: 321–347. https://doi.org/10.1128/CMR.00068-15; PMid:26960938 PMCid:PMC4786888

16. Falagas ME, Vouloumanou EK, Togias AG et al. (2010). Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 65: 1862–1877. https://doi.org/10.1093/jac/dkq237; PMid:20587612

17. Gopichand P, Agarwal G, Natarajan M et al. (2019). In vitro effect of fosfomycin on multi-drug-resistant gram-negative bacteria causing urinary tract infections. Infect. Drug Resist. 12: 2005–2013. https://doi.org/10.2147/IDR.S207569; PMid:31372008 PMCid:PMC6628599

18. Gupta K, Hooton TM, Naber KG et al. (2011). International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 52: e103–120. https://doi.org/10.1093/cid/ciq257; PMid:21292654

19. Honda J, Okubo Y, Kusaba M et al. (1998). Fosfomycin (FOM: 1 R-2S-e-poxypropylphosphonic acid) suppress the production of IL-8 from monocytes via the suppression of neutrophil function. Immunopharmacology. 39: 149–155. https://doi.org/10.1016/S0162-3109(98)00003-4

20. Huttner A, Kowalczyk A, Turjeman A et al. (2018). Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women. A randomized clinical trial. JAMA. 319 (17): 1781–1789. https://doi.org/10.1001/jama.2018.3627; PMid:29710295 PMCid:PMC6134435

21. Kang C-I, Kim J, Park DW et al. (2018). Clinical practice guidelines for the antibiotic treatment of community-acquired urinary tract infections. Infect Chemother. 50 (1): 67–100. https://doi.org/10.3947/ic.2018.50.1.67; PMid:29637759 PMCid:PMC5895837

22. Karlowsky JA, Denisuik AJ, Lagace-Wiens PRS et al. (2014). In vitro activity of fosfomycin against Escherichia coli isolated from patients with urinary tract infections in Canada as part of the CANWARD surveillance study. Antimicrob Agents Chemotherapy.58 (2): 1252–1256. https://doi.org/10.1128/AAC.02399-13; PMid:24323476 PMCid:PMC3910835

23. Krause R, Patruta S, Daxbock F et al. (2001). The effect of fosfomycin on neutrophil function. J Antimicrob. Chemother. 47: 141–146. https://doi.org/10.1093/jac/47.2.141; PMid:11157896

24. Matsumoto T, Tateda K, Miyazaki S et al. (1999). Fosfomycin alters lipopolysaccharide-induced inflammatory cytokine production in mice. Antimicrob Agents Chemother. 43: 697–698. https://doi.org/10.1128/AAC.43.3.697; PMid:10049293 PMCid:PMC89186

25. Michalopoulos AS, Livaditis IG, Gougoutas V. (2011). The revival of fosfomycin. Int J Infect Dis. 15: e732–739. https://doi.org/10.1016/j.ijid.2011.07.007; PMid:21945848

26. Mody L, Juthani-Mehta M. (2014). Urinary tract infections in older women: a clinical review. JAMA. 311 (8): 844–854. https://doi.org/10.1001/jama.2014.303; PMid:24570248 PMCid:PMC4194886

27. Morikawa K, Oseko F, Morikawa S et al. (1993). Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro. Antimicrob. Agents Chemother. 37: 2684–2687. https://doi.org/10.1128/AAC.37.12.2684; PMid:7509146 PMCid:PMC192778

28. Morikawa K, Watabe H, Araake M et al. (1996). Modulatory effect of antibiotics on cytokine production by human monocytes in vitro. Antimicrob Agents Chemother. 40: 1366–1370. https://doi.org/10.1128/AAC.40.6.1366; PMid:8726002 PMCid:PMC163332

29. Naber KG, Schito G, Botto H et al. (2008). Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy. Eur Urol. 54: 1164–1175. https://doi.org/10.1016/j.eururo.2008.05.010; PMid:18511178

30. Nicolle L, Anderson PAM, Conly J et al. (2006). Uncomplicated urinary tract infection in women. Current practice and the effect of antibiotic resistance on empiric treatment. Can Fam Physician. 52: 612–618.

31. Paladin Labs. 2007. Monurol package insert. Paladin Labs, Quebec, Canada.

32. Patel SS, Balfour JA, Bryson HM. (1997). Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs. 53: 637–656. https://doi.org/10.2165/00003495-199753040-00007; PMid:9098664

33. Perez Fernandez P, Herrera I, Martinez P et al. (1995). Enhancement of the susceptibility of Staphylococcus aureus to phagocytosis after treatment with fosfomycin compared with other antimicrobial agents. Chemotherapy.41: 45–49. https://doi.org/10.1159/000239323; PMid:7875021

34. Pezzlo MA. (2014). Laboratory diagnosis of urinary tract infections: guidelines, challenges, and innovations. Clin Microbiol Newsletter. 36 (12): 87–93. https://doi.org/10.1016/j.clinmicnews.2014.05.003

35. Roussos N, Karageorgopoulos DE, Samonis G et al. (2009). Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. Int J Antimicrob. Agents. 34: 506–515. https://doi.org/10.1016/j.ijantimicag.2009.08.013; PMid:19828298

36. Urinary tract infection (lower): antimicrobial prescribing. (2018). NICE guideline NG 109. URL: www.nice.org.uk/guidance/ng109

37. Wang A, Niran P, Malone MA et al. (2013). Urinary tract infections. Primary Care: Clinics in Office Practice. 40 (3): 687–706. https://doi.org/10.1016/j.pop.2013.06.005; PMid:23958364

38. Yokota S, Okabayashi T, Yoto Y et al. (2010). Fosfomycin suppresses RS-virus-induced Streptococcus pneumoniae and Haemophilus influenzae adhesion to respiratory epithelial cells via the platelet-activating factor receptor. FEMS Microbiol. Lett. 310: 84–90. https://doi.org/10.1111/j.1574-6968.2010.02049.x; PMid:20629755 PMCid:PMC7110074

39. Zhanel GG, Walkty AJ, Karlowsky JA. (2016). Fosfomycin: a first-line oral therapy for acute uncomplicated cystitis. Can. J Infect. Dis. Med. Microbiol. 2016, Article ID 2082693. https://doi.org/10.1155/2016/2082693; PMid:27366158 PMCid:PMC4904571