Antimicrobial susceptibility studies
In vitro susceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin

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Abstract

We evaluated the in vitro activity of fosfomycin against 75 clinical isolates of vancomycin-resistant enterococci (VRE). Using the NCCLS breakpoint for susceptibility of urinary tract isolates to fosfomycin (MIC ≥ 256), 51 out of 52 Enterococcus faecium and all Enterococcus faecalis isolates tested were susceptible or intermediate to fosfomycin.

Introduction

Fosfomycin is a phosphonic acid bactericidal agent that acts primarily by inhibiting bacterial cell wall peptidoglycan synthesis (Patel et al., 1997). The compound is active against many urinary pathogens including Escherichia coli, Staphylococcus saprophyticus and many strains of enterococci Hamilton-Miller 1991, The Medical Letter and Therapeutics 1997, Patel 1997. Published MICs90 of fosfomycin against enterococci are 52.3 μg/ml (Patel et al., 1997). There is little information on the activity of fosfomycin vs. VRE. In recent years, enterococci have emerged as significant clinical pathogens with both intrinsic and acquired resistance to a number of antibiotics. In view of the limited treatment options for VRE, in this study we evaluated the in vitro susceptibilities of fosfomycin versus 75 clinical isolates of VRE.

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Materials and methods

We tested 75 clinical isolates of VRE. The strains of VRE used in this study were clinical isolates obtained from hospitalized patients from 1991 to 1998 from different U.S. hospitals. All isolates were resistant to multiple other agents including ampicillin and high-levels of gentamicin. Fifty-two isolates were E. faecium and 23 isolates were E. faecalis. Twenty-two isolates were from urine, 18 isolates were from unknown/other sources, 16 isolates were from blood, 12 isolates were from

Results

The MICs for the 52 E. faecium isolates ranged from 8 to 256 μg/ml. The MICs for the 23 E. faecalis isolates ranged from 16 to 64 μg/ml (broth microdilution) (see Table 1). Results of E-strip tests were more consistent with broth microdilution for E. faecalis isolates (MIC range 12–64 μg/ml). Although the overall susceptibility rate (67%) was similar among the E. faecium isolates some variation was seen between the broth microdilution and E-test results. None of the E. faecium isolates were

Discussion

Fosfomycin has been available in Europe for many years as a parenteral compound, fosfomycin disodium. Two other compounds are available for oral administration: fosfomycin calcium and fosfomycin trometamol. Fosfomycin trometamol is the result of systematic studies aimed at improving the biopharmaceutical properties and, among all the phosphonic acid derivatives, is the compound with the most favorable bioavailability profile.

Fosfomycin trometamol has the attributes considered desirable in an

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  • Fosfomycin resistance among vancomycin-resistant enterococci owing to transfer of a plasmid harbouring the fosB gene

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    Citation Excerpt :

    It has also been reported that fosfomycin could be a potentially useful drug for the treatment of infections caused by vancomycin-resistant enterococci (VRE) [1–3]; however, there is little information on the activity of fosfomycin against VRE. Perri et al. evaluated the in vitro activity of fosfomycin against clinical VRE isolates and showed that fosfomycin might be considered for the treatment of uncomplicated VRE lower urinary tract infections [3]. Conjugative transfer of a fosfomycin resistance marker encoded on a plasmid was described in 1980 [4].

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