Determination of dalbavancin epidemiological cut-off value (ECOFFs) for Enterococcus faecium

Background: Dalbavancin is a semi-synthetic lipoglycopeptide antibiotic that shows potent activity against gram-positive bacteria including staphylococci, streptococci and enterococci. Although extensive data are available on the in vitro activity of dalbavancin for E. faecalis, comprehensive data on E. faecium are generally scarce due to the global dissemination of vanA-positive and glycopeptide resistant VRE. In Central Europe, however, a continuing shift from vanA-type vancomycin-resistance to vanB-type resistance has been observed from 2006 onwards. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van genotypes, with particular focus on vanB-type E. faecium. Methods: Susceptibility testing for 25 van-negative, 50 vanA-positive and 101 vanB-positive clinical E. faecium isolates was performed using broth microdilution (BMD) as a reference method. In addition, dalbavancin MICs were determined by MIC gradient strips. All isolates were routinely sequenced and typed by MLST and cgMLST. ECOFFs were determined by the use of ECOFFinder and a threshold of 99%.Results: For vanB type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values not higher than 0.125 mg/L. ECOFFs for van-negative and vanB-positive isolates were 0.5 mg/l and 0.25 mg/L respectively (BMD). In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. Conclusion: We demonstrated the potent in vitro activity of dalbavancin against vancomycin-susceptible and vanB-type E. faecium. On the basis of the observed wildtype distribution, a dalbavancin MIC of 0.25 mg/L can be suggested as suitable ECOFF for these isolates.