•CC17 Enterococcus faecium has emerged as a pandemic clone.•Vancomycin resistance is a critical issue.•Dissemination of CC17 E. faecium in the human–animal–environment interface has been ...documented.•Current epidemiology of vancomycin-resistant E. faecium.•Therapeutic alternatives to vancomycin for vancomycin-resistant CC17 E. faecium.
Enterococcus faecium is a robust opportunistic pathogen that is most commonly found as a commensal of the human and animal gut but can also survive in the environment. Since the introduction and use of antimicrobials, E. faecium has been found to rapidly acquire resistance genes that, when expressed, can effectively circumvent the effects of most antimicrobials. The rapid acquisition of multiple antimicrobial resistances has led to the adaptation of specific E. faecium clones in the hospital environment, collectively known as clonal complex 17 (CC17). CC17 E. faecium are responsible for a significant proportion of hospital-associated infections, which can cause severe morbidity and mortality. Here we review the history of E. faecium from commensal to a significant hospital-associated pathogen, its robust phenotypic characteristics, commonly used laboratory typing schemes, and antimicrobial resistances with a focus on vancomycin and its associated mechanism of resistance. Finally, we review the global epidemiology of vancomycin-resistant E. faecium and potential solutions to problems faced in public health.
In Australia in 2015, Candida auris sternal osteomyelitis was diagnosed in a 65-year-old man with a history of intensive care treatment in Kenya in 2012 and without a history of cardiac surgery. The ...isolate was South Africa clade III. Clinicians should note that C. auris can cause low-grade disease years after colonization.
•Correlation between large-genome vancomycin-resistant E. faecium strains and decreased virulence factors with outbreaks.•Gain/loss of antimicrobial-resistant genes appear to contribute most to ...rise/decline of an outbreak strain.
The first outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in Western Australia was recorded in 2001. A state-wide infection control effort that oversaw patient screening and transfers successfully terminated the outbreak within six months; however, the outbreak re-emerged two years later. Over the two outbreaks, the vanB-positive multilocus sequence type (ST) 173 E. faecium strain was isolated from 201 patients.
Our objective was to identify differences in genetic traits leading to successful transmission of ST173 VREfm compared with non-ST173 VREfm isolated during the same period. We also aimed to describe the changes observed in the ST173 VREfm genome collected during the two outbreaks.
Virulence factors ecbA, fss3, psaA and scm identified in the non-ST173 isolates were largely absent in the ST173 isolates. The esp gene was not identified beyond 45% coverage for any isolate in this study. In terms of resistance genes, tet(U) was identified in 94.7% of ST173 VREfm isolated in the first outbreak but was largely absent in ST173 VREfm isolated in the second outbreak and in non-ST173 VREfm. Seven ST173 VREfm isolates (Clade A) carried dfrG but not tet(M) resistance genes. The average genome size of ST173 VREfm isolated in the first outbreak was significantly larger than the genome size of ST173 VREfm isolated in the second outbreak.
The reduced number of virulence factors in ST173 isolates may explain the low infection and high colonization rates observed during the outbreak. In addition, isolates with larger genomes were found to be associated with outbreaks.
Whole-genome sequencing is essential to many facets of infectious disease research. However, technical limitations such as bias in coverage and tagmentation, and difficulties characterising genomic ...regions with extreme GC content have created significant obstacles in its use. Illumina has claimed that the recently released DNA Prep library preparation kit, formerly known as Nextera Flex, overcomes some of these limitations. This study aimed to assess bias in coverage, tagmentation, GC content, average fragment size distribution, and de novo assembly quality using both the Nextera XT and DNA Prep kits from Illumina. When performing whole-genome sequencing on Escherichia coli and where coverage bias is the main concern, the DNA Prep kit may provide higher quality results; though de novo assembly quality, tagmentation bias and GC content related bias are unlikely to improve. Based on these results, laboratories with existing workflows based on Nextera XT would see minor benefits in transitioning to the DNA Prep kit if they were primarily studying organisms with neutral GC content.
Carbapenem-resistant Enterobacteriaceae (CRE) are a pressing public health issue due to limited therapeutic options to treat such infections. CREs have been predominantly isolated from humans and ...environmental samples and they are rarely reported among companion animals. In this study we report on the isolation and plasmid characterization of carbapenemase (IMP-4) producing Salmonella enterica Typhimurium from a companion animal. Carbapenemase-producing S. enterica Typhimurium carrying bla
was identified from a systemically unwell (index) cat and three additional cats at an animal shelter. All isolates were identical and belonged to ST19. Genome sequencing revealed the acquisition of a multidrug-resistant IncHI2 plasmid (pIMP4-SEM1) that encoded resistance to nine antimicrobial classes including carbapenems and carried the bla
-qacG-aacA4-catB3 cassette array. The plasmid also encoded resistance to arsenic (MIC-150 mM). Comparative analysis revealed that the plasmid pIMP4-SEM1 showed greatest similarity to two bla
carrying IncHI2 plasmids from Enterobacter spp. isolated from humans in China. This is the first report of CRE carrying a bla
gene causing a clinical infection in a companion animal, with presumed nosocomial spread. This study illustrates the broader community risk entailed in escalating CRE transmission within a zoonotic species such as Salmonella, and in a cycle that encompasses humans, animals and the environment.
Over the last three decades, hospital adapted clonal complex (CC) 17 strains of Enterococcus faecium have acquired and exchanged antimicrobial resistance genes leading to the widespread resistance to ...clinically important antimicrobials globally. In Australia, a high prevalence of vancomycin resistance has been reported in E. faecium in the last decade.
In this study, we determined the phylogenetic relationship and genetic characteristics of E. faecium collected from hospitalized patients with blood stream infections throughout Australia from 2015 to 2017 using high throughput molecular techniques.
Using single nucleotide polymorphism based phylogenetic inference, three distinct clusters of isolates were observed with additional sub-clustering. One cluster harboured mostly non-CC17 isolates while two clusters were dominant for the vanA and vanB operons.
The gradual increase in dominance of the respective van operon was observed in both the vanA and vanB dominant clusters suggesting a strain-van operon affinity. The high prevalence of the van operon within isolates of a particular sub-cluster was linked to an increased number of isolates and 30-day all-cause mortality. Different dominant sub-clusters were observed in each region of Australia. Findings from this study can be used to put future surveillance data into a broader perspective including the detection of novel E. faecium strains in Australia as well as the dissemination and evolution of each strain.
The global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the ...PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to screen for genetic traits that might have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to search for potential virulence genes associated with bacteraemia. Based on single nucleotide polymorphism phylogenetics we revealed two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002-2017) revealed an observed gain in accessory genes amongst the clone's population. GWAS analysis on the bacteraemia isolates identified two gene candidates that have previously been associated to this kind of infection. Although this hypothesis was not tested here, it is possible that the emergence of a ST93-IV clade containing additional virulence genes might be related to the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. More importantly, our data also demonstrated that GWAS can reveal candidate genes for further investigations on the pathogenesis and evolution of MRSA strains within a same lineage.
Using whole-genome sequencing, we identified a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type (ST) 398 type V (5C2&5) isolate (typically found in China) in ...Australia in 2017. This CA-MRSA ST398 variant was highly virulent, similar to other related CA-MRSAs of ST398. This strain should be monitored to prevent more widespread dissemination.
Enterococcus faecium is an opportunistic pathogen that has become one of the leading causes of hospital acquired infection that are resistant to multiple critically important antimicrobials.
The ...objective of the study was to describe the molecular characteristics and relationship between major strains of E. faecium harbouring the van operon and to determine if the strains had increasing virulence and antimicrobial resistance determinants over time.
E. faecium harbouring the van operon detected using PCR from surveillance rectal swabs of patients that were admitted to high-risk units at a Perth teaching hospital from 2001 to 2015 were retrospectively analysed using a whole genome sequencing and bioinformatics approach.
ST18, ST78, ST80, ST173, ST203 and ST555 were identified as the major STs accounting for 93.7% of E. faecium isolates. Except for ST173, major STs identified at Royal Perth Hospital (RPH) have been reported across Australia and internationally. Isolates from each ST formed independently branched phylogenetic clusters with each harbouring unique virulence and antimicrobial resistance profiles. Depending on the ST, different genes conferring resistance to similar antimicrobial classes were identified. Except for ST80 which harboured the vanA type operon, all major strains harboured the vanB operon conferring only vancomycin resistance.
Major strains of E. faecium isolated over 15-years showed unique virulome and resistome profiles with no indication of increasing virulence or antimicrobial resistance determinants. Strains were distantly related and the acquisition of different genes encoding similar antimicrobial resistances suggest the independent evolution of each strain.
The whole genome sequences of all isolates from this study are accessible from the NCBI-SRA database under project number PRJNA575940 and PRJNA524213. Published reference sequence Aus0004 was obtained from NCBI-SRA under project number PRJNA86649 DOI:10.1128/JB.00259–12
In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a ...penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.
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