738. Activity of Fosfomycin Against Carbapenem Resistant Enterobacteriaceae
Session: Poster Abstract Session: Antimicrobials: Resistance Mechanisms
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
  • Keepers_Fosfomycin_IDWeek Poster 738.pdf (3.1 MB)
  • Background: Fosfomycin (FOS) is a cell wall active agent that inhibits the MurA enzyme involved in peptidoglycan synthesis. It has broad spectrum bactericidal activity against Gram-negative organisms, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci.  FOS is approved by US-FDA for treatment of uncomplicated urinary tract infections (UTIs) and has gained renewed interest as a treatment for UTIs caused by Gram-negative organisms that are increasingly resistant to other antibiotics including carbapenem-resistant Enterobacteriaceae (CRE).

    Methods: This study included 47 CRE isolates, including Klebsiella pneumoniae (36), Enterobacter cloacae (6), Escherichia coli (4), and Serratia marcescens (1).  CRE were defined by resistance to imipenem (MIC ≥4 µg/mL). FOS MICs were determined by agar dilution in agar medium containing 25 µg/mL glucose-6-phosphate according to CLSI guidelines.  β-lactamase genes were identified using Check-points microarrays.

    Results: Of the 47 CRE isolates tested, 38 were susceptible (80.9%), 2 were intermediate, and 6 were resistant to fosfomycin as interpreted using current CLSI breakpoints (≤64 µg/mL susceptible).  Five of the six FOS-resistant isolates were K. pneumoniae and one isolate was E. cloacae. There was no unique or common pattern of carbapenemases or β-lactamases among the FOS-resistant isolates.  FOS MICs ranged from 1 to >256 μg/mL, the MIC50 was 16 μg/mL, and the MIC90 was 256 μg/mL. Imipenem MICs ranged from 4 to >128 µg/mL.  All isolates expressed at least one carbapenemase, KPC or OXA, or a metallo-β-lactamase. The majority of isolates (87%) expressed one or more additional β-lactamases including extended spectrum β-lactamases (ESBLs).

    Conclusion: In this study 80.9% of CRE isolates tested were susceptible to FOS. A wide variety of β-lactamase genes were present among these CRE isolates, and there did not appear to be any associations between any particular genes and resistance or susceptibility to FOS. The mechanisms responsible for FOS resistance in these isolates remain to be determined.  These data support the potential for use of fosfomycin as a treatment for urinary tract infections caused by carbapenemase-resistant Enterobacteriaceae.

    Tiffany R. Keepers, PhD1, Chris Celeri1, Marcela Gomez1, Donald Biek, PhD1, Rolf Wagenaar2 and Ian A. Critchley, PhD1, (1)Cerexa, Inc. (a wholly owned subsidiary of Forest Laboratories, Inc., New York, NY), Oakland, CA, (2)Forest Laboratories, Inc., New York, NY


    T. R. Keepers, Cerexa, Inc.: Employee, Salary and stock options

    C. Celeri, Cerexa, Inc.: Employee, Salary

    M. Gomez, Cerexa, Inc: Employee, Salary

    D. Biek, Cerexa, Inc: Employee, Salary and stock options and stock in Forest Laboratories, Inc.

    R. Wagenaar, Forest Laboratories, Inc: Employee and Shareholder, Salary and stock options and stock in Forest Laboratories, Inc

    I. A. Critchley, Cerexa, Inc: Employee, Salary and stock and stock options in Forest Laboratories, Inc

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.