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Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study

Authors: Philippa C. Matthews, Lucinda K. Barrett, Stephanie Warren, Nicole Stoesser, Mel Snelling, Matthew Scarborough, Nicola Jones

Published in: BMC Infectious Diseases | Issue 1/2016

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Abstract

Background

Fosfomycin is increasingly called upon for the treatment of multi drug-resistant (MDR) organisms causing urinary tract infection (UTI). We reviewed oral fosfomycin use for UTI treatment in a large UK hospital. The primary goal was to audit our clinical practice against current national guidelines. Secondary aims were to identify factors associated with treatment failure, and to investigate the potential for using fosfomycin in patients with co-morbidities.

Methods

We retrospectively studied 75 adult patients with UTI who received 151 episodes of treatment with fosfomycin from March 2013 to June 2015. We collected clinical data from our electronic patient record, and microbiology data pre- and post- fosfomycin treatment. We recorded additional data for patients receiving prolonged courses in order to make a preliminary assessment of safety and efficacy. We also reviewed >18,000 urinary tract isolates of Escherichia coli and Klebsiella spp. processed by our laboratory over the final year of our study period to determine the prevalence of fosfomycin resistance.

Results

There was a significant increase in fosfomycin treatment episodes over the course of the study period. Co-morbidities were present in 71 % of patients. The majority had E. coli infection (69 %), of which 59 % were extended spectrum beta-lactamase (ESBL)-producers. Klebsiella infections were more likely than E. coli to fail treatment, and more likely to be reported as fosfomycin resistant in cases of relapse following treatment. There were no adverse events in five patients treated with prolonged fosfomycin. Among all urinary isolates collected over a year, fosfomycin resistance was documented in 1 % of E. coli vs. 19 % of Klebsiella spp. (p < 0.0001).

Conclusions

We report an important role for oral fosfomycin for MDR UTI treatment in a UK hospital population, and based on the findings from this study, we present our own local guidelines for its use. We present preliminary data suggesting that fosfomycin is safe and effective for use in patients with complex comorbidities and over prolonged time periods, but may be less effective against Klebsiella than E. coli.
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Literature
1.
go back to reference Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014;28(1):1–13.CrossRefPubMed Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014;28(1):1–13.CrossRefPubMed
2.
go back to reference Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269–84.CrossRefPubMedPubMedCentral Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269–84.CrossRefPubMedPubMedCentral
3.
4.
go back to reference Rosso-Fernandez C, Sojo-Dorado J, Barriga A, Lavin-Alconero L, Palacios Z, Lopez-Hernandez I, Merino V, Camean M, Pascual A, Rodriguez-Bano J, et al. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ Open. 2015;5(3):e007363.CrossRefPubMedPubMedCentral Rosso-Fernandez C, Sojo-Dorado J, Barriga A, Lavin-Alconero L, Palacios Z, Lopez-Hernandez I, Merino V, Camean M, Pascual A, Rodriguez-Bano J, et al. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ Open. 2015;5(3):e007363.CrossRefPubMedPubMedCentral
5.
go back to reference Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. Jama. 2014;312(16):1677–84.CrossRefPubMed Grigoryan L, Trautner BW, Gupta K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. Jama. 2014;312(16):1677–84.CrossRefPubMed
6.
go back to reference Meier S, Weber R, Zbinden R, Ruef C, Hasse B. Extended-spectrum beta-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections: an increasing challenge for antimicrobial therapy. Infection. 2011;39(4):333–40.CrossRefPubMed Meier S, Weber R, Zbinden R, Ruef C, Hasse B. Extended-spectrum beta-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections: an increasing challenge for antimicrobial therapy. Infection. 2011;39(4):333–40.CrossRefPubMed
7.
go back to reference Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2014;34(8):845–57.CrossRefPubMed Reffert JL, Smith WJ. Fosfomycin for the treatment of resistant gram-negative bacterial infections. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2014;34(8):845–57.CrossRefPubMed
8.
go back to reference Mikuniya T, Kato Y, Ida T, Maebashi K, Monden K, Kariyama R, Kumon H. Treatment of Pseudomonas aeruginosa biofilms with a combination of fluoroquinolones and fosfomycin in a rat urinary tract infection model. J Infect Chemother. 2007;13(5):285–90.CrossRefPubMed Mikuniya T, Kato Y, Ida T, Maebashi K, Monden K, Kariyama R, Kumon H. Treatment of Pseudomonas aeruginosa biofilms with a combination of fluoroquinolones and fosfomycin in a rat urinary tract infection model. J Infect Chemother. 2007;13(5):285–90.CrossRefPubMed
9.
go back to reference Sultan A, Rizvi M, Khan F, Sami H, Shukla I, Khan HM. Increasing antimicrobial resistance among uropathogens: Is fosfomycin the answer? Urology annals. 2015;7(1):26–30.CrossRefPubMedPubMedCentral Sultan A, Rizvi M, Khan F, Sami H, Shukla I, Khan HM. Increasing antimicrobial resistance among uropathogens: Is fosfomycin the answer? Urology annals. 2015;7(1):26–30.CrossRefPubMedPubMedCentral
10.
go back to reference Pullukcu H, Tasbakan M, Sipahi OR, Yamazhan T, Aydemir S, Ulusoy S. Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Escherichia coli-related lower urinary tract infections. Int J Antimicrob Agents. 2007;29(1):62–5.CrossRefPubMed Pullukcu H, Tasbakan M, Sipahi OR, Yamazhan T, Aydemir S, Ulusoy S. Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Escherichia coli-related lower urinary tract infections. Int J Antimicrob Agents. 2007;29(1):62–5.CrossRefPubMed
11.
go back to reference Senol S, Tasbakan M, Pullukcu H, Sipahi OR, Sipahi H, Yamazhan T, Arda B, Ulusoy S. Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother. 2010;22(5):355–7.CrossRefPubMed Senol S, Tasbakan M, Pullukcu H, Sipahi OR, Sipahi H, Yamazhan T, Arda B, Ulusoy S. Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother. 2010;22(5):355–7.CrossRefPubMed
12.
go back to reference Qiao LD, Zheng B, Chen S, Yang Y, Zhang K, Guo HF, Yang B, Niu YJ, Wang Y, Shi BK, et al. Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study. BMJ Open. 2013;3(12):e004157.CrossRefPubMedPubMedCentral Qiao LD, Zheng B, Chen S, Yang Y, Zhang K, Guo HF, Yang B, Niu YJ, Wang Y, Shi BK, et al. Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study. BMJ Open. 2013;3(12):e004157.CrossRefPubMedPubMedCentral
17.
go back to reference Garcia-Tello A, Gimbernat H, Redondo C, Arana DM, Cacho J, Angulo JC. Extended-spectrum beta-lactamases in urinary tract infections caused by Enterobacteria: understanding and guidelines for action. Actas Urol Esp. 2014;38(10):678–84.CrossRefPubMed Garcia-Tello A, Gimbernat H, Redondo C, Arana DM, Cacho J, Angulo JC. Extended-spectrum beta-lactamases in urinary tract infections caused by Enterobacteria: understanding and guidelines for action. Actas Urol Esp. 2014;38(10):678–84.CrossRefPubMed
18.
go back to reference Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis. 2008;46(7):1069–77.CrossRefPubMed Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis. 2008;46(7):1069–77.CrossRefPubMed
19.
go back to reference Neuner EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012;56(11):5744–8.CrossRefPubMedPubMedCentral Neuner EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012;56(11):5744–8.CrossRefPubMedPubMedCentral
21.
go back to reference Karageorgopoulos DE, Wang R, Yu XH, Falagas ME. Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. J Antimicrob Chemother. 2012;67(2):255–68.CrossRefPubMed Karageorgopoulos DE, Wang R, Yu XH, Falagas ME. Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. J Antimicrob Chemother. 2012;67(2):255–68.CrossRefPubMed
22.
go back to reference Grayson ML, Macesic N, Trevillyan J, Ellis AG, Zeglinski PT, Hewitt NH, Gardiner BJ, Frauman AG. Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs. Clin Infect Dis. 2015;61(7):1141–3.CrossRefPubMed Grayson ML, Macesic N, Trevillyan J, Ellis AG, Zeglinski PT, Hewitt NH, Gardiner BJ, Frauman AG. Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs. Clin Infect Dis. 2015;61(7):1141–3.CrossRefPubMed
23.
go back to reference Rodriguez-Bano J, Alcala JC, Cisneros JM, Grill F, Oliver A, Horcajada JP, Tortola T, Mirelis B, Navarro G, Cuenca M, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med. 2008;168(17):1897–902.CrossRefPubMed Rodriguez-Bano J, Alcala JC, Cisneros JM, Grill F, Oliver A, Horcajada JP, Tortola T, Mirelis B, Navarro G, Cuenca M, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med. 2008;168(17):1897–902.CrossRefPubMed
24.
go back to reference Tandogdu Z, Wagenlehner FM. Global epidemiology of urinary tract infections. Curr Opin Infect Dis. 2016;29(1):73–9.CrossRefPubMed Tandogdu Z, Wagenlehner FM. Global epidemiology of urinary tract infections. Curr Opin Infect Dis. 2016;29(1):73–9.CrossRefPubMed
25.
go back to reference Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents. 2011;37(5):415–9.CrossRefPubMed Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents. 2011;37(5):415–9.CrossRefPubMed
26.
go back to reference Cho YH, Jung SI, Chung HS, Yu HS, Hwang EC, Kim SO, Kang TW, Kwon DD, Park K. Antimicrobial susceptibilities of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin. Int Urol Nephrol. 2015;47(7):1059–66.CrossRefPubMed Cho YH, Jung SI, Chung HS, Yu HS, Hwang EC, Kim SO, Kang TW, Kwon DD, Park K. Antimicrobial susceptibilities of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin. Int Urol Nephrol. 2015;47(7):1059–66.CrossRefPubMed
27.
go back to reference Tung C, Cheon C. Single-dose Fosfomycin Tromethamine for Treatment of Urinary Tract Infection In Hong Kong Women: a Preliminary Prospective Study. Hong Kong J Gynaecol Obstet Midwifery. 2012;12:37–42. Tung C, Cheon C. Single-dose Fosfomycin Tromethamine for Treatment of Urinary Tract Infection In Hong Kong Women: a Preliminary Prospective Study. Hong Kong J Gynaecol Obstet Midwifery. 2012;12:37–42.
28.
go back to reference Jansaker F, Frimodt-Moller N, Sjogren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother. 2014;69(3):769–72.CrossRefPubMed Jansaker F, Frimodt-Moller N, Sjogren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother. 2014;69(3):769–72.CrossRefPubMed
29.
go back to reference Los-Arcos I, Pigrau C, Rodriguez-Pardo D, Fernandez-Hidalgo N, Andreu A, Larrosa N, Almirante B. Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis. Antimicrob Agents Chemother. 2015;60(3):1854–8.CrossRefPubMed Los-Arcos I, Pigrau C, Rodriguez-Pardo D, Fernandez-Hidalgo N, Andreu A, Larrosa N, Almirante B. Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis. Antimicrob Agents Chemother. 2015;60(3):1854–8.CrossRefPubMed
30.
go back to reference Oteo J, Bautista V, Lara N, Cuevas O, Arroyo M, Fernandez S, Lazaro E, de Abajo FJ, Campos J, Spanish E-E-NSG. Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. J Antimicrob Chemother. 2010;65(11):2459–63.CrossRefPubMed Oteo J, Bautista V, Lara N, Cuevas O, Arroyo M, Fernandez S, Lazaro E, de Abajo FJ, Campos J, Spanish E-E-NSG. Parallel increase in community use of fosfomycin and resistance to fosfomycin in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. J Antimicrob Chemother. 2010;65(11):2459–63.CrossRefPubMed
31.
go back to reference Sorlozano A, Jimenez-Pacheco A, de Dios Luna Del Castillo J, Sampedro A, Martinez-Brocal A, Miranda-Casas C, Navarro-Mari JM, Gutierrez-Fernandez J. Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study. Am J Infect Control. 2014;42(10):1033–8.CrossRefPubMed Sorlozano A, Jimenez-Pacheco A, de Dios Luna Del Castillo J, Sampedro A, Martinez-Brocal A, Miranda-Casas C, Navarro-Mari JM, Gutierrez-Fernandez J. Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study. Am J Infect Control. 2014;42(10):1033–8.CrossRefPubMed
Metadata
Title
Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study
Authors
Philippa C. Matthews
Lucinda K. Barrett
Stephanie Warren
Nicole Stoesser
Mel Snelling
Matthew Scarborough
Nicola Jones
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1888-1

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