Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium.

Robert E Weber,Bernd Neumann,Franziska Layer,Michael Kresken,Carola Fleige,Guido Werner

doi:10.3390/antibiotics10080915

Abstract

Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. In recent years, there has been a continuing shift from vanA-type to vanB-type vancomycin-resistance in enterococci in Central Europe. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van-genotypes, with particular focus on vanB-type E. faecium. Dalbavancin susceptibility was determined for 25 van-negative, 50 vanA-positive, and 101 vanB-positive clinical E. faecium isolates (typed by cgMLST). Epidemiological Cut-Off Values (ECOFFs) were determined using ECOFFinder. For vanB-type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values no 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. In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. 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 a tentative ECOFF for E. faecium.

Highlights

Enterococci are intestinal commensals in many animals and humans
The strain collection contained a total of 101 vanB-positive, 50 vanA-positive, and 25 van-negative E. faecium isolates belonging to 16 MLST and 74 cgMLST types (Supplementary Table S1 and Figure S1)
Dalbavancin MICs of vanB-positive E. faecium isolates (n = 101) tended to be one dilution below from what could be determined for van-negative E. faecium isolates (MIC50 = 0.032 mg/L, MIC90 = 0.064 mg/L) (Table 1)

Summary

Introduction

Enterococci are intestinal commensals in many animals and humans. few members of this genus are important nosocomial pathogens that are capable of causing severe infections in critically ill and immunocompromised patients. Enterococcus faecium isolates have received increased public health attention due to a dramatic increase of related infections and the accumulation of antibiotic resistance determinants [1]. No distinct geographical patterns could be observed across Europe, and even in countries with similar VRE rates, trends may differ with regard to the dissemination of different strain backgrounds and van genotype dynamics. Countries such as Denmark and Switzerland showed rising VRE trends, mainly due to an increased incidence of vanA-type E. faecium clonal types like ST203 and ST796 [4,5,6]. Other countries such as Germany and Poland reported a high prevalence of vanB-type resistance, which was preferably found among the E. faecium isolates of ST78 or ST117 [7,8,9]

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