title: Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms.
abstract: Fosfomycin has shown promising in vitro activity against multidrug-resistant (MDR) urinary pathogens; however, clinical data are lacking. We conducted a retrospective chart review to describe the microbiological and clinical outcomes of urinary tract infections (UTIs) with MDR pathogens treated with fosfomycin tromethamine. Charts for 41 hospitalized patients with a urine culture for an MDR pathogen who received fosfomycin tromethamine from 2006 to 2010 were reviewed. Forty-one patients had 44 urinary pathogens, including 13 carbapenem-resistant Klebsiella pneumoniae (CR-Kp), 8 Pseudomonas aeruginosa, and 7 vancomycin-resistant Enterococcus faecium (VRE) isolates, 7 extended-spectrum beta-lactamase (ESBL) producers, and 9 others. In vitro fosfomycin susceptibility was 86% (median MIC, 16 μg/ml; range, 0.25 to 1,024 μg/ml). Patients received an average of 2.9 fosfomycin doses per treatment course. The overall microbiological cure was 59%; failure was due to either relapse (24%) or reinfection UTI (17%). Microbiological cure rates by pathogen were 46% for CR-Kp, 38% for P. aeruginosa, 71% for VRE, 57% for ESBL producers, and 100% for others. Microbiological cure (n = 24) was compared to microbiological failure (n = 17). There were significantly more solid organ transplant recipients in the microbiological failure group (59% versus 21%; P = 0.02). None of the patients in the microbiological cure group had a ureteral stent, compared to 24% of patients within the microbiological failure group (P = 0.02). Fosfomycin demonstrated in vitro activity against UTIs due to MDR pathogens. For CR-KP, there was a divergence between in vitro susceptibility (92%) and microbiological cure (46%). Multiple confounding factors may have contributed to microbiological failures, and further data regarding the use of fosfomycin for UTIs due to MDR pathogens are needed.
authors.affiliation: Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio, USA. neunere@ccf.org
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Neuner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sekeres
authors.forename: Gerri S
authors.initials: GS
authors.lastname: Hall
authors.forename: David
authors.initials: D
authors.lastname: van Duin
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D012189:Retrospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D005578:Fosfomycin; D001618:beta-Lactamases