Experience with Fosfomycin for Treatment of Urinary Tract Infections Due to Multidrug-Resistant Organisms

Abstract

c 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 g/ml; range, 0.25 to 1,024 g/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.

Carbapenem-resistant Enterobacteriaceae in special populations: Solid organ transplant recipients, stem cell transplant recipients, and patients with hematologic malignancies

“…In a study of 13 patients with CRE UTI who were treated with fosfomycin, only 6 achieved a microbiologic cure and 3 developed fosfomycin resistance on therapy. 80 In this study, as well as a study demonstrating that fosfomycin was effective against extended-spectrumb-lactamase-producing E. coli UTIs, fosfomycin was administered as a 3 g dose every 48 hours for 3 total doses. 81 However, the optimal dosing and duration of therapy for CRE UTIs is unknown.…”

Successful treatment of lower urinary tract infections with oral fosfomycin: a report of three cases

“…A 92% in vitro fosfomycin susceptibility was observed with a corresponding microbiological cure of 46% (6/13 patients). Most patients who had treatment failure were immunosuppressed or had ureteral stents suggesting caution in using fosfomycin monotherapy in these types of patients (1) .…”

“…Thus, the absence of a catheter might have contributed to the successful treatment of these three patients. Furthermore, fosfomycin in combination with other antibiotics, e.g., colistin, gentamicin, or carbapenems, might be able to eradicate biofi lms caused by gram-negative bacteria (1) .…”

“…The parenteral formulation has been used in combination therapy to treat a wide range of infections including pneumonia and septicemia with cure rates >80% (12) . Given its low rates of resistance and the available evidence, fosfomycin may serve as a useful option for oral treatment of MDR uropathogens (1) . Surprisingly, data regarding in vitro and in vivo activity of fosfomycin against KPC-producing K. pneumoniae isolates have been lacking until recently.…”

“…In particular, data regarding the use of fosfomycin for the treatment of infections caused by contemporary MDR gram-negative pathogens are warranted to further evaluate the optimal clinical use of this revived antimicrobial agent (1) . Studies supporting the use of this drug as monotherapy for these infections are limited.…”