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Use of In Vitro Vancomycin Testing Results to Predict Susceptibility to Oritavancin, a New Long-Acting Lipoglycopeptide.
Antimicrob Agents Chemother. 2015 Feb 9;
Authors: Jones RN, Turnidge JD, Moeck G, Arhin FF, Mendes RE
Abstract
Oritavancin is a recently approved lipoglycopeptide antimicrobial agent with activity against gram-positive (GP) pathogens. Its extended serum elimination half-life and concentration-dependent killing enable single-dose treatment of acute bacterial skin and skin structure infections. At the time of regulatory approval, new agents including oritavancin are not offered in the most widely used susceptibility testing devices, and therefore may require application of surrogate testing using a related antimicrobial to infer susceptibility. To evaluate vancomycin as a predictive susceptibility marker for oritavancin, 26,993 recent GP organisms from United States and European hospitals were tested by reference MIC methods. Organisms included Staphylococcus aureus (SA), coagulase-negative staphylococci (CoNS), β-haemolytic streptococci (βHS), viridans group streptococci (VGS) and enterococci (ENT). These five major pathogen groups were analyzed by comparing results at FDA-approved susceptible breakpoints for both drugs, as well as those suggested by epidemiological cut-off values and supported by pharmacokinetic/pharmacodynamic analyses. Vancomycin susceptibility was highly accurate (98.1-100.0%) as a surrogate for oritavancin susceptibility among indicated pathogen species. Furthermore, direct MIC comparisons showed high oritavancin potencies, with vancomycin/oritavancin MIC90 results of 1/0.06, 2/0.06, 0.5/0.12,1/0.06 and >16/0.06 μg/ml for SA, CoNS, βHS, VGS and ENT, respectively. In conclusion, vancomycin demonstrated acceptable accuracy as a surrogate marker for predicting oritavancin susceptibility when tested against indicated pathogens. In contrast, 93.3% of vancomycin-non-susceptible enterococci had oritavancin MIC values at ≤0.12 μg/ml indicating poor predictive value of VAN for ORI resistance against these organisms. Until commercial oritavancin susceptibility testing devices are readily available, isolates that test vancomycin-susceptible can be inferred as susceptible to ORI using FDA-approved breakpoints.
PMID: 25666152 [PubMed - as supplied by publisher]