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Oritavancin combinations with beta-lactams against multidrug-resistant Staphylococcus aureus and vancomycin-resistant enterococci.
Antimicrob Agents Chemother. 2016 Feb 1;
Authors: Smith JR, Yim J, Raut A, Rybak MJ
Abstract
BACKGROUND: Oritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro data suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated BLs combined with oritavancin against MRSA and VRE.
METHODS: Oritavancin MICs were determined for 30 strains, five each of MRSA, daptomycin-nonsusceptible MRSA (DNS), vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), VRE faecalis, and VRE faecium. Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin for MRSA or ceftaroline, ampicillin, or ertapenem for VRE was evaluated for lethal synergy in 24-hour time-kill assays against each phenotype. Oritavancin at 0.5 x MIC was combined with BLs at the lesser of 0.5 x MIC or biologic free peak. Synergy was defined as ≥2 log10 CFU/ml difference between combination and most active single agent at 24 hours.
RESULTS: Oritavancin MICs were ≤0.125 μg/ml for all MRSA except 3 VISA with MICs of 0.25 μg/ml. Oritavancin VRE MICs were 0.03-0.125 μg/ml. Oritavancin + ceftaroline was synergistic against all phenotypes and statistically superior to all other combinations against DNS, hVISA, and MRSA (p<0.02). Oritavancin + cefazolin and oritavancin + nafcillin were also synergistic against all strains. VRE 8019 revealed synergy between oritavancin and all BLs, while VRE R7164 demonstrated synergy between oritavancin and ampicillin or ertapenem, but not ceftaroline.
CONCLUSIONS: The data support potential use of oritavancin + BLs, especially oritavancin + ceftaroline, against MRSA, while VRE did not demonstrate a similar amount of synergy.
PMID: 26833159 [PubMed - as supplied by publisher]