title: Comparison of fosfomycin to ertapenem for outpatient or step-down therapy of extended-spectrum β-lactamase urinary tract infections.
abstract: Extended-spectrum β-lactamase (ESBL) enzymes cause resistance to common β-lactam antibiotics and are associated with poor outcomes. Management of ESBL urinary tract infections (UTIs) is challenging given the limited treatment options available outside the hospital setting. In this study, the primary endpoint of UTI-related 30-day hospital re-admission or emergency department/clinic revisit rates was compared for fosfomycin and ertapenem outpatient ESBL UTI treatments. A retrospective cohort study was performed on patients with ESBL UTIs treated with outpatient fosfomycin or ertapenem from January 2010 to February 2015. Inclusion criteria were age ≥18 years, outpatient treatment with fosfomycin or ertapenem for symptomatic ESBL UTI, and positive urine cultures with microbiologically proven ESBL-producing bacteria. A non-inferiority margin of 0.15 was selected to detect a difference in the primary endpoint. Patient and infection characteristics were compared. A sensitivity analysis with propensity score matching was performed. In total, 178 patients were included (89 fosfomycin-treated and 89 ertapenem-treated). Ertapenem-treated patients received longer outpatient antibiotic treatment (10 days vs. 6 days; P <0.001). ESBL isolates identified were 149 Escherichia coli (83.7%), 26 Klebsiella spp. (14.6%) and 3 other (1.7%). Common dosage regimens were oral dose of 3 g fosfomycin every 72 h (62%), oral dose of 3 g fosfomycin every 48 h (23%) and intravenous dose of 1 g ertapenem daily (76%). The thirty-day re-admission/revisit rates for fosfomycin and ertapenem were 14.6% vs. 13.5% (1.1% difference; 97.5% CI, -0.11 to 0.13). Fosfomycin was non-inferior to ertapenem for treating outpatient ESBL UTIs and should be considered as appropriate step-down therapy for these infections.
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Veve
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Wagner
authors.affiliation: Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Kenney
authors.affiliation: Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Grunwald
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; Henry Ford Hospital, Detroit, MI, USA. Electronic address: sldavis@wayne.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Davis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000145:classification / Q000201:enzymology*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D000077727:Ertapenem; D005260:Female; D005578:Fosfomycin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D010359:Patient Readmission; D012189:Retrospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy*; D055815:Young Adult; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D005578:Fosfomycin; D001618:beta-Lactamases; D000077727:Ertapenem
keywords: Antimicrobial stewardship; ESBL; Ertapenem; Extended-spectrum β-lactamase; Fosfomycin; UTI