263. In-vitro Activity of Vancomycin Combined with Colistin versus Multi-drug Resistant E. coli and K. pneumoniae Isolates Producing NDM Metallo-carbapenemases
Session: Poster Abstract Session: Antimicrobial Susceptibility and Resistance
Friday, October 21, 2011
Room: Poster Hall B1
Background: Multi-drug resistant (MDR) Gram-negative bacteria raise significant treatment dilemmas. The recent identification of plasmid encoded metallo-β-lactamases (NDM-1) on transmissible MDR plasmids in Enterobacteriaceae is particularly concerning as strains harbouring these have rapidly spread across the globe. With many isolates now increasingly reported resistant to all commonly used antimicrobials, clinicians are forced to use un-orthodox combination treatments. We recently identified strong synergy between colistin and glycopeptides versus MDR strains of A. baumannii. Here we report a similar activity when these drugs are used versus carbapenemase producing Enterobacteriaceae.

Methods: Isolates were identified by MALDI-Tof and susceptibility testing was performed using the MicroScan Walkaway system. Multiplex PCRs were used to detect TEM, SHV, CTX-M, pAmpC, GES, PER, VEB, KPC, IMP, VIM, SIM, SPM and GIM β-lactamases. Full coding sequences of genes encoding NDM carbapenemases were amplified cloned and sequenced. Susceptibility of each isolate to colistin (COL) and vancomycin (VAN) alone and in combination was determined in microtitre plate checkerboard assays. Fractional Inhibitory Concentration (FIC) and Susceptibility Breakpoint indices (SBPI) were calculated with a FICI of < 0.5 for the well with the lowest FIC and a SBPI of > 2 taken as evidence of in-vitro synergy.  

Results: Six isolates (4 E. coli, 2 K. pneumoniae) were studied. Each strain contained NDM in combination with CTX-M1, OXA-1, TEM or SHV-like genes and was resistant to all antimicrobials tested with the exception of COL and tigecycline. Although the MIC of VAN was >256 mg/L for each isolate this was reduced to < 1 mg/L when tested in the presence of COL. FICIs calculated from checkerboards were all ≤ 0.5 (0.126 - 0.5) indicative of potent synergy. SBPIs ranged from 8 – 18 suggesting the combination may be useful at therapeutically achievable concentrations

Conclusion: Potent synergy was observed when COL was combined with VAN. With few therapeutic options for the treatment of carbapenemase producing organisms, clinical evaluation of the efficacy and safety of polymyxin / glycopeptide combinations following these in-vitro findings is needed.


Subject Category: A. Antimicrobial agents and Resistance

David Wareham, PhD, 4 Newark Street, Queen Mary University London, Whitechapel, London, United Kingdom, Lynette Phee, Barts and The London NHS Trust, London, United Kingdom and Michael Hornsey, Queen Mary University London, London, United Kingdom

Disclosures:

D. Wareham, None

L. Phee, None

M. Hornsey, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.