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Outbreaks caused by vancomycin-resistant Enterococcus faecium in hematology and oncology departments: A systematic review.

ABSTRACT: Background:Vancomycin-resistance in Enterococcus faecium (VRE) poses a major threat in health care settings. It is well known that patients in hematology and oncology departments are especially at risk of nosocomial VRE acquisition. This systematic review of the literature provides data on the main sources, transmission modes and potential risk factors for VRE acquisition as well as appropriate infection control measures in order to terminate such nosocomial outbreaks. Methods:Data on nosocomial VRE outbreaks on hematology and oncology wards was retrieved from the Outbreak Database and PubMed. Results:A total of 35 VRE outbreaks describing 757 affected patients and 77 deaths were included in this review. The most frequent site of pathogen detection were stool samples or rectal swabs (57% of all isolation sites), followed by blood cultures (30%). The most common outbreak source was an index patient. The main modes of transmission were 1) hands of health care workers, 2) contact to a contaminated environment and 3) patient-to-patient contact. The most common risk factor for VRE positivity was prior antibiotic treatment. The most common infection control measures performed were screening and isolating or cohorting of patients. Conclusion:A rational use of antibiotics in hematology and oncology units is recommended in order to reduce selection pressure on resistant pathogens such as VRE. In addition the importance of hand hygiene should be stressed to all staff whenever possible.

SUBMITTER: Ulrich N

PROVIDER: S-EPMC5753762 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Outbreaks caused by vancomycin-resistant <i>Enterococcus faecium</i> in hematology and oncology departments: A systematic review.

Ulrich Nikos N Vonberg Ralf-Peter RP Gastmeier Petra P

Heliyon 20171228 12

<h4>Background</h4>Vancomycin-resistance in <i>Enterococcus faecium</i> (VRE) poses a major threat in health care settings. It is well known that patients in hematology and oncology departments are especially at risk of nosocomial VRE acquisition. This systematic review of the literature provides data on the main sources, transmission modes and potential risk factors for VRE acquisition as well as appropriate infection control measures in order to terminate such nosocomial outbreaks.<h4>Methods< ...[more]

PMID: 29322099

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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:Background: Vancomycin-resistant Enterococcus faecium (VREfm) is a successful nosocomial pathogen. The current molecular method recommended in the Netherlands for VREfm typing is based on core genome Multilocus sequence typing (cgMLST), however, the rapid emergence of specific VREfm lineages challenges distinguishing outbreak isolates solely based on their core genome. Here, we explored if a detailed molecular characterisation of mobile genetic elements (MGEs) and accessory genes could support and expand the current molecular typing of VREfm isolates sharing the same genetic background, enhancing the discriminatory power of the analysis. Materials/Methods: The genomes of 39 VREfm and three vancomycin-susceptible E. faecium (VSEfm) isolates belonging to ST117/CT24, as assessed by cgMLST, were retrospectively analysed. The isolates were collected from patients and environmental samples from 2011 to 2017, and their genomes were analysed using short-read sequencing. Pangenome analysis was performed on de novo assemblies, which were also screened for known predicted virulence factors, antimicrobial resistance genes, bacteriocins, and prophages. Two representative isolates were also sequenced using long-read sequencing, which allowed a detailed analysis of their plasmid content. Results: The cgMLST analysis showed that the isolates were closely related, with a minimal allelic difference of 10 between each cluster's closest related isolates. The vanB-carrying transposon Tn1549 was present in all VREfm isolates. However, in our data, we observed independent acquisitions of this transposon. The pangenome analysis revealed differences in the accessory genes related to prophages and bacteriocins content, whilst a similar profile was observed for known predicted virulence and resistance genes. Conclusion: In the case of closely related isolates sharing a similar genetic background, a detailed analysis of MGEs and the integration point of the vanB-carrying transposon allow to increase the discriminatory power compared to the use of cgMLST alone. Thus, enabling the identification of epidemiological links amongst hospitalised patients.

Dataset Information

Outbreaks caused by vancomycin-resistant Enterococcus faecium in hematology and oncology departments: A systematic review.

Publications

Outbreaks caused by vancomycin-resistant <i>Enterococcus faecium</i> in hematology and oncology departments: A systematic review.

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