title: Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK. p.matthews@doctors.org.uk.|Nuffield Department of Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. p.matthews@doctors.org.uk.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Matthews
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Lucinda K
authors.initials: LK
authors.lastname: Barrett
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Warren
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.|Nuffield Department of Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stoesser
authors.affiliation: Pharmacy Department, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Mel
authors.initials: M
authors.lastname: Snelling
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Scarborough
authors.affiliation: Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Jones
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D005578:Fosfomycin / Q000008:administration & dosage*; D006801:Humans; D007709:Klebsiella / Q000187:drug effects; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: Antibacterial resistance; Antibacterials; Escherichia coli; Fosfomycin; Gram-negative; UTI; Uropathogens; Urosepsis