Dataset Information

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

ABSTRACT:

Background

The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT).

Methods

The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90?days.

Results

Mortality was similar between VRE- (n?=?39) and VSE- (n?=?138) group after 30 (p?=?0.44) or 90?days (p?=?0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFA_Non-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders.

Conclusion

Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population.

Trial registration

This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

SUBMITTER: Dubler S

PROVIDER: S-EPMC6995054 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

Dubler S S Lenz M M Zimmermann S S Richter D C DC Weiss K H KH Mehrabi A A Mieth M M Bruckner T T Weigand M A MA Brenner T T Heininger A A

Antimicrobial resistance and infection control 20200131 1

<h4>Background</h4>The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT).<h4>Methods</h4>The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medic ...[more]

PMID: 32005223

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Project description:Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.

Project description:BackgroundIn addition to an overall rise in vancomycin-resistant Enterococcus faecium (VREfm), an increase in certain strain types marked by sequence type (ST) and cluster type (CT) has been reported in Germany over the past few years. Outbreak analyses at Charité - Universitätsmedizin Berlin revealed the frequent occurrence of VREfm ST117 CT71 isolates in 2017 and 2018. To investigate whether ST117 CT71 have emerged in recent years or whether these strains have been circulating for a longer time, we retrospectively analyzed non-outbreak strains that occurred between 2008 and 2018 to identify frequent STs and CTs.MethodsIn total, 120 VREfm isolates obtained from clinical and surveillance cultures from the years 2008, 2013, 2015, and 2018 were analyzed. Thirty isolates per year comprising the first 7-8 non-outbreak isolates of each quarter of the respective year were sequenced using whole genome sequencing. MLST and cgMLST were determined as well as resistance genes and virulence factors. Risk factors for VREfm ST117 were analyzed in a multivariable analysis with patient characteristics as possible confounders.ResultsThe percentage of VREfm of type ST117 increased from 17% in 2008 to 57% in 2018 (p = 0.012). In 2008, vanA genotype accounted for 80% of all ST117 isolates compared to 6% in 2018. VanB CT71 first appeared in 2018 and predominated over all other ST117 at 43% (p < 0.0001). The set of resistance genes (msrC, efmA, erm(B), dfrG, aac(6')-Ii, gyrA, parC and pbp5) and virulence factors (acm, esp, hylEfm, ecbA and sgrA) in CT71 was also found in other ST117 non-CT71 strains, mainly in CT36. The study population did not differ among the different calendar years analyzed in terms of age, gender, length of stay, or ward type (each p > 0.2).ConclusionThis study revealed an increase in ST117 strains from 2008 to 2018, accompanied by a shift toward CT71 strains with the vanB genotype in 2018. We did not detect resistance or virulence traits in CT71 that could confer survival advantage compared to other CTs among ST117 strains. To date, it is not clear why ST117 and in particular strain type ST117 CT71 predominates over other strains.

Dataset Information

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

Background

Methods

Results

Conclusion

Trial registration

Publications

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

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