Low Proportion of Linezolid and Daptomycin Resistance Among Bloodborne Vancomycin-Resistant Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus Infections in Europe.

Niklas Willrich,Tim Eckmanns,Olaniyi Ayobami,Robby Markwart,Guido Werner

doi:10.3389/fmicb.2021.664199

Abstract

Vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant health burden. We investigated linezolid and daptomycin resistance among VREF and MRSA in the EU/EEA between 2014 and 2018. Descriptive statistics and multivariable logistic regression were used to analyze 6,949 VREF and 35,131 MRSA blood isolates from patients with bloodstream infection. The population-weighted mean proportion of linezolid resistance in VREF and MRSA between 2014 and 2018 was 1.6% (95% CI 1.33–2.03%) and 0.28% (95% CI 0.32–0.38%), respectively. Daptomycin resistance in MRSA isolates was similarly low [1.1% (95% CI 0.75–1.6%)]. On the European level, there was no temporal change of daptomycin and linezolid resistance in MRSA and VREF. Multivariable regression analyses showed that there was a higher likelihood of linezolid and daptomycin resistance in MRSA (aOR: 2.74, p < 0.001; aOR: 2.25, p < 0.001) and linezolid in VREF (aOR: 1.99, p < 0.001) compared to their sensitive isolates. The low proportion of linezolid and daptomycin resistance in VREF and MRSA suggests that these last-resort antibiotics remain effective and will continue to play an important role in the clinical management of these infections in Europe. However, regional and national efforts to contain antimicrobial resistance should continue to monitor the trend through strengthened surveillance that includes genomic surveillance for early warning and action.

Highlights

MATERIALS AND METHODSStaphylococcus aureus and Enterococcus faecium are Grampositive pathogens that frequently colonize the skin, nostrils, and gut of humans with potential for invasive infections in humans (Fisher and Phillips, 2009)
Number of isolates (%) Number of isolates tested against linezolid (% tested) Number of isolates tested against daptomycin (% tested) Number of vancomycinresistant Enterococcus faecium (VREF)/Methicillin-resistant Staphylococcus aureus (MRSA) isolates (%*) Year of sampling 2014 (n, %) 2015 (n, %) 2016 (n, %) 2017 (n, %) 2018 (n, %) European regions North (n, %) West (n, %) South (n, %) East (n, %) Gender of patients Female (n, %) Male (n, %) NA (n, %) Sex ratio (f/m) Age of patients
We found that there was a trend of higher linezolid resistance proportions among VREF isolates in intensive care units (ICU) compared to non-ICUs, this difference was not statistically significant [1.94% vs. 1.36%, p = 0.107; adjusted Odds Ratio (OR): 1.36, p = 0.174] (Table 2)

Summary

Introduction

MATERIALS AND METHODSStaphylococcus aureus and Enterococcus faecium are Grampositive pathogens that frequently colonize the skin, nostrils, and gut of humans with potential for invasive infections in humans (Fisher and Phillips, 2009). In Europe and many other countries across the world, Enterococcus spp. and S. aureus infections are commonly observed among hospital patients with high vancomycin and methicillin resistance proportions, respectively (Lakhundi and Zhang, 2018; García-Solache and Rice, 2019). These multidrug-resistant pathogens have been associated with significant mortality and morbidity in several healthcare settings (Caballero-Granado et al, 2001; Pinholt et al, 2014; Boncagni et al, 2015; Brady et al, 2017; Nelson et al, 2017; Kramer et al, 2018; Cassini et al, 2019). Recent studies have demonstrated the rising trend of vancomycin resistance in Enterococcus spp., especially in E. faecium, and its pervasiveness across Europe (Markwart et al, 2019; Ayobami et al, 2020a)

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