Fosfomycin Susceptibility in Multidrug-Resistant Enterobacteriaceae Species and Vancomycin-Resistant Enterococci...

Broad-spectrum antibiotics are often used to treat urinary tract infections (UTIs) due to drug-resistant species of Enterobacteriaceae and Enterococcus (e.g., organisms producing extended-spectrum β-lactamase [ESBL] or AmpC β-lactamase, as well as vancomycin-resistant enterococci [VRE]). However, this type of therapy can promote selection of resistant organisms and may necessitate venous access. Fosfomycin is an orally administered, single-dose antibiotic for the treatment of uncomplicated UTI. Little is known about its microbiologic activity against urinary isolates, including in southwestern Ontario, since fosfomycin susceptibility testing is not routinely performed.

To explore a cost-effective alternative for the treatment of lower UTIs caused by multidrug-resistant Enterobacteriaceae and VRE organisms resistant to usual first-line therapies by determining fosfomycin susceptibility rates.

Urinary isolates were collected prospectively from November 2015 to April 2016 at 3 hospitals in southwestern Ontario. Susceptibility testing was completed according to guidelines of the Clinical and Laboratory Standards Institute, with interpretation by zone of inhibition (as diameter in millimetres). Patients 18 years of age or older with isolation of multidrug-resistant Enterobacteriaceae or VRE were eligible for inclusion. Urinary isolates from these patients were subjected to susceptibility testing. The primary outcome was the rate of fosfomycin susceptibility of these isolates.

A total of 137 urinary isolates were tested: 106 positive for ESBL-or AmpC β-lactamase-producing Enterobacteriaceae (95 Escherichia coli, 11 Klebsiella spp.) and 31 positive for vancomycin-resistant Enterococcus faecium. Susceptibility rates for ESBL- and AmpC β-lactamase-producing E. coli were 100% for ertapenem, 96% for fosfomycin, 83% for nitrofurantoin, 72% for gentamicin, 56% for trimethoprim-sulfamethoxazole, and 14% for ciprofloxacin. Susceptibility rates of vancomycin-resistant E. faecium urinary isolates were 100% for linezolid, 81% for fosfomycin, 68% for tetracycline, 6% for ampicillin, 3% for penicillin, and 0% for both nitrofurantoin and ciprofloxacin.

Given susceptibility rates at the study institutions, fosfomycin was deemed the most reliable oral option for the treatment of lower UTI in patients with suspected or documented multidrug-resistant uropathogens.