Use of Fosfomycin for the Treatment of Urinary Tract Infections

Background: Fosfomycin is a phosphonic acid derivative originally isolated in 1969 that possesses a unique mechanism of action, inhibiting enolpyruvyl transferase and preventing the formation of peptidogylcan subunits.  As antimicrobial resistance continues to rise, clinicians are turning to this older antibiotic for the treatment of urinary tract infections (UTIs).  Despite demonstrating a broad spectrum of activity in vitro few clinical data exist to support the use of fosfomycin for the treatment of multi-drug resistant (MDR) infections.

Objective: To assess the role of fosfomycin for the treatment of UTIs at an academic medical center.

Methods: This study was a retrospective analysis of patients admitted to the Hospital of the University of Pennsylvania who received at least one dose of fosfomycin for the treatment of a UTI.  Basic demographic data was collected as well as clinical response, microbiologic outcomes, and all-cause inpatient mortality.

Results: Thirty-four cases were reviewed from the time period of January 1, 2008 through August 31, 2010.  The mean age was 66 (range 33 to 88) and 68% were female.  The most common causative organisms were K. pneumoniae (35%), E. coli (32%), and Enterococcus spp. (18%).  Fosfomycin was utilized in 74% of patients because of the presence of MDR organisms isolated from urine cultures, in 20% of patients because of allergies to other potentially effective antibiotics, and in 6% for other undocumented reasons.  The average length of fosfomycin therapy was 2 doses (range 1 to 6).  Of the 14 patients with documented signs and symptoms, 72% demonstrated a response to therapy.  Sixteen patients had repeat urine cultures, 31% of which showed eradication of the organism while 44% remained positive.  In all but one of these cases, K. pneumoniae was the organism that was not eradicated, including two cases that became resistant to fosfomycin immediately after therapy was completed.  Two patients died during hospital admission.

Conclusions: These results show, in a small population, that outcomes of fosfomycin therapy are highly variable.  While 72% of patients had a clinical response, 44% of patients demonstrated microbiologic failure.  These data warrant further investigation into the efficacy of fosfomycin therapy for the treatment of MDR organisms.