Prevalence Of Vancomycin-resistant Enterococcus Faecium Research Articles

Emergence and ongoing outbreak of ST80 vancomycin-resistant Enterococcus faecium in Guangdong province, China from 2021 to 2023: a multicenter, time-series and genomic epidemiological study

ABSTRACT Background: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. Methods: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. Results: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20−50% in 2023 (p < 0.0001), but not in the other five provinces. Two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid harbouring a vanA cassette, which was embedded in a Tn1546-like structure flanked by IS1678 and ISL3. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission. Conclusions: We revealed an ongoing outbreak of ST80 VREfm with a new vanA-harbouring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.

Factors affecting vancomycin-resistant Enterococcus faecium colonization of in-hospital patients in different wards.

The prevalence of vancomycin-resistant Enterococcus faecium (VRE) infection at a medical center in Eastern Taiwan rose to 80.6%, exceeding the average prevalence of 55.6% among all medical centers nationwide during the same period. In recent years, the number of cases of VRE infection detected among hospitalized patients has increased annually. However, most of these patients in different wards are asymptomatic carriers. Therefore, restricting active screening to high-risk units will not improve the current situation, and it is necessary to review the risk factors for VRE colonization to provide a reference for future infection control policies. Between 2014 and 2019, there were 3188 VRE-positive cultures reported at our institution, as per the electronic medical records system. In the medical and surgical wards, patients who received penicillin (odds ratios [ORs]: 2.84 and 4.16, respectively) and third-generation cephalosporins (ORs: 3.17 and 6.19, respectively) were at higher risk of VRE colonization. In intensive care units, the use of carbapenems (OR: 2.08) was the most significant variable. This study demonstrated that the risk factors for VRE colonization differed between wards. Thus, policies should be established according to the attributes of patients in each ward, and active screening tests should be performed according to individual risks, instead of a policy for comprehensive mass screening.

Molecular epidemiology of bacteraemic vancomycin-resistant Enterococcus faecium isolates and in vitro activities of SC5005 and other comparators against these isolates collected from a medical centre in northern Taiwan, 2019-2020.

The global prevalence of vancomycin-resistant Enterococcus faecium (VREfm) highlights the need for new anti-enterococcal agents. Here, we assessed the molecular epidemiology of clinical VREfm bacteraemic isolates from a medical centre in northern Taiwan in 2019-2020 and to evaluate their susceptibility to last-line antibiotics and a new antimicrobial agent, SC5005. The molecular epidemiology of VREfm was investigated using van genotyping, MLST and PFGE. The susceptibilities of VREfm strains to antibiotics and SC5005 were determined using the agar dilution and broth microdilution methods. The capability of E. faecium to develop resistance to antibiotics and SC5005 was evaluated using frequency of resistance and multipassage resistance assays. The mode of action of SC5005 was assessed by time-kill, bacterial membrane integrity and membrane potential assays. All 262 VREfm isolates harboured vanA gene, and the most prevalent sequence type was ST17 (51%, n = 134, 84 pulsotypes), followed by ST78 (25%, n = 65, 54 pulsotypes). Additionally, we identified four new STs (ST2101, ST2102, ST2135 and ST2136) and observed the arrival of multidrug-resistant ST1885 in Taiwan. Moreover, SC5005 was effective against all VREfm isolates, including those non-susceptible to last-line antibiotics. SC5005 can disrupt and depolarize the bacterial membrane to kill E. faecium without detectable resistance. The findings provide insights into the latest epidemiology and resistance profiles of bacteraemic-causing VREfm in northern Taiwan. Additionally, SC5005 has the potential for development as a new therapeutic to treat VREfm infections.

Infection prevention and control policies in hospitals and prevalence of highly resistant microorganisms: an international comparative study

BackgroundThere are differences in infection prevention and control (IPC) policies to prevent transmission of highly resistant microorganisms (HRMO). The aim of this study is to give an overview of the IPC policy of six European hospitals and their HRMO prevalence, to compare the IPC policies of these hospitals with international guidelines, and to investigate the hospitals’ adherence to their own IPC policy.MethodsThe participating hospitals were located in Salzburg (Austria), Vienna (Austria), Kayseri (Turkey), Piraeus (Greece), Rome (Italy) and Rotterdam (The Netherlands). Data were collected via an online survey. Questions were aimed at prevalence rates in the years 2014, 2015, 2016 of carbapenemase-producing Klebsiella pneumoniae (CPK), carbapenemase-producing Pseudomonas aeruginosa (CPPA), vancomycin-resistant Enterococcus faecium (VRE) and hospitals’ IPC policies of 2017. Implemented IPC measures (i.e. with a self-reported adherence of > 90%) were counted (26 points maximal).ResultsThe self-reported prevalence of CPK per year was low in the Austrian and Dutch hospitals and high in the Turkish and Greek hospitals. CPPA was highly prevalent in the Turkish hospital only, while the prevalence of VRE in four hospitals, except the Austrian hospitals which reported lower prevalence numbers, was more evenly distributed. The Dutch hospital had implemented the most IPC measures (n = 21), the Turkish and Greek hospitals the least (n = 14 and 7, respectively).ConclusionHospitals with the highest self-reported prevalence of CPK and CPPA reported the least implemented IPC measures. Also, hospitals with a higher prevalence often reported a lower adherence to own IPC policy.

Curcumin carbon dots inhibit biofilm formation and expression of esp and gelE genes of Enterococcusfaecium

The increasing prevalence of vancomycin-resistant Enterococcus faecium, along with the ability of this bacterium to form biofilm on biotic surfaces and medical devices, has created a serious challenge. Therefore, the development of new antibacterial agents is an urgent need. In this study, curcumin carbon dots (Cur-CDs) were synthesized by a one-step hydrothermal method, and its antibacterial and antibiofilm effects were investigated. By broth microdilution method, the minimal inhibitory concentration (MIC) against vancomycin-resistant and sensitive clinical isolates of Enterococcus faecium (two clinical isolates in total) and standard strain of Enterococcus faecalis ATCC 29212 was determined, which were 1000, 1000, and 125 μg/ml, respectively. The inhibitory effect of Cur-CDs on biofilm formation of vancomycin-resistant E. faecium clinical isolates were evaluated by microtiter plate assay. Cur-CDs (1000 μg/ml) significantly prevented (p = 0.009) the biofilm formation of E. faecium isolates. Real-time PCR results showed that Cur-CDs (1000 μg/ml) significantly downregulated the expression of esp and gelE genes (p = 0.001 and p = 000000002, respectively) in clinical isolates of E. faecium, while Cur-CDs did not affect acm gene expression (p = 0.086). This study revealed that Cur-CDs can be effective antibacterial and antibiofilm agents against vancomycin-resistant and biofilm producer E. faecium, which makes them interesting candidates for treating or preventing bacterial infections.

The use of core genome multilocus sequence typing to determine the duration of vancomycin-resistant Enterococcus faecium outbreaks.

The prevalence of vancomycin-resistant Enterococcus faecium has increased rapidly, and in Denmark, we are facing an endemic outbreak situation in hospitals. The aim of this study was to use whole-genome sequencing (WGS) and core genome multilocus sequencing typing (cgMLST) to determine the duration of VREfm outbreaks and thereby evaluate the effect of our infection control strategies. We included all VREfm isolates from six hospitals in the Capital Region of Denmark that were sequenced between 2012 and 2020. Ward data were collected from our laboratory information system. A ward outbreak was defined as two patient samples from the same ward within a period of 30 days belonging to the same cgMLST cluster. cgMLST complex types were determined using Ridom SeqSphere v7.2.3, where a maximum of 20 allelic differences between isolates defines a cluster. We included 1690 patient isolates between 2012 and 2020. Our collection consisted of 45 unique clusters and 227 ward outbreaks. The median duration of outbreaks was 20 days. We reported a median outbreak duration of VREfm outbreaks based on WGS data to be 20 days, and thus concluded that our infection control precautions are adequate.

Correlation between Nosocomial Carriage of Vancomycin-Resistant Enterococci and Antimicrobial Use in Taiwan.

A rapid increase of nosocomial vancomycin-resistant enterococci (VRE) from 23.3% in 2009 to 44.5% in 2018 among all the medical centers in Taiwan was found. The aim of the study was to explore the relationship between antimicrobial usage and prevalence of VRE. We conducted the study between January 2010 and December 2019 in a tertiary teaching hospital in Taiwan. Antibiotic consumption was expressed as defined daily doses (DDDs) per 1,000 patient-days (PDs). The trend in antibiotic consumption and VRE prevalence were analyzed by regression analysis with yearly data. Pearson's correlation analysis was used to determine the relationship between antibiotic consumption and the prevalence of VRE. The total consumption of antibiotics increased significantly from 450.6 DDDs/1,000 PDs in 2010 to 520.1 DDDs/1,000 PDs in 2019 (P = 0.013). Positive correlations were found between the prevalence of vancomycin-resistant Enterococcus faecium and the consumption of amoxicillin/clavulanate, vancomycin, and carbapenems, which included meropenem (P < 0.05). The increase in total VRE prevalence was significantly correlated with increased consumption of vancomycin and carbapenems, which included meropenem (P < 0.05). This 10-year study in a hospital demonstrated changes in antimicrobial use, which may have affected VRE prevalence in the hospital. We found a rise in nosocomial VRE prevalence was associated with the use of specific antimicrobial agents.

Characterization of Clinical Vancomycin-Resistant Enterococcus faecium Isolated in Eastern Hungary.

The aim of our study was to characterize and elicit the genetic relatedness of emerging vancomycin-resistant enterococci (VRE) isolated between 2012 and 2015 at a teaching hospital in Debrecen, Hungary. Altogether 43 nonduplicate vancomycin-resistant Enterococcus faecium (VREfm) clinical isolates were obtained. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for species identification. Isolates showed 100% resistance to ampicillin and ciprofloxacin while 81.4% were resistant to gentamicin. PCR analysis revealed the presence of VanB in 40 and VanA in 3 isolates. Among ace, agg, and esp virulence genes only esp was found in seven cases. Modified microtiter-plate test showed 13 weak and 4 moderate biofilm producer isolates. Pulsed-field gel electrophoresis revealed nine pulsotypes. According to multilocus sequence typing all of the tested isolates belonged to clonal complex 17 (CC17). We report on the alarming emergence of multidrug-resistant VREfm belonging to CC17 at a tertiary hospital in Eastern Hungary. This is the first report of sequence types 412 and 364 from this region. Although outbreak did not occur the increasing prevalence of VREfm is of concern and dissemination must be prevented with proper infection control measures and regular VRE screening.

Genomic Surveillance of Enterococcus faecium Reveals Limited Sharing of Strains and Resistance Genes between Livestock and Humans in the United Kingdom

Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of nosocomial infection and is categorized as high priority by the World Health Organization global priority list of antibiotic-resistant bacteria. In the past, livestock have been proposed as a putative reservoir for drug-resistant E. faecium strains that infect humans, and isolates of the same lineage have been found in both reservoirs. We undertook cross-sectional surveys to isolate E. faecium (including VREfm) from livestock farms, retail meat, and wastewater treatment plants in the United Kingdom. More than 600 isolates from these sources were sequenced, and their relatedness and antibiotic resistance genes were compared with genomes of almost 800 E. faecium isolates from patients with bloodstream infection in the United Kingdom and Ireland. E. faecium was isolated from 28/29 farms; none of these isolates were VREfm, suggesting a decrease in VREfm prevalence since the last UK livestock survey in 2003. However, VREfm was isolated from 1% to 2% of retail meat products and was ubiquitous in wastewater treatment plants. Phylogenetic comparison demonstrated that the majority of human and livestock-related isolates were genetically distinct, although pig isolates from three farms were more genetically related to human isolates from 2001 to 2004 (minimum of 50 single-nucleotide polymorphisms [SNPs]). Analysis of accessory (variable) genes added further evidence for distinct niche adaptation. An analysis of acquired antibiotic resistance genes and their variants revealed limited sharing between humans and livestock. Our findings indicate that the majority of E. faecium strains infecting patients are largely distinct from those from livestock in this setting, with limited sharing of strains and resistance genes.IMPORTANCE The rise in rates of human infection caused by vancomycin-resistant Enterococcus faecium (VREfm) strains between 1988 to the 2000s in Europe was suggested to be associated with acquisition from livestock. As a result, the European Union banned the use of the glycopeptide drug avoparcin as a growth promoter in livestock feed. While some studies reported a decrease in VREfm in livestock, others reported no reduction. Here, we report the first livestock VREfm prevalence survey in the UK since 2003 and the first large-scale study using whole-genome sequencing to investigate the relationship between E. faecium strains in livestock and humans. We found a low prevalence of VREfm in retail meat and limited evidence for recent sharing of strains between livestock and humans with bloodstream infection. There was evidence for limited sharing of genes encoding antibiotic resistance between these reservoirs, a finding which requires further research.

Reduction of nosocomial bloodstream infections and nosocomial vancomycin-resistant Enterococcus faecium on an intensive care unit after introduction of antiseptic octenidine-based bathing

Vancomycin-resistant Enterococcus faecium (VRE) is emerging in German intensive care units (ICUs). On a 32-bed surgical ICU at a university hospital, increasing numbers of nosocomial cases occurred despite enforcement of hand hygiene and environmental disinfection. To introduce universal octenidine-based bathing in order to reduce the burden of VRE. Between January 2012 and March 2014, patients were screened for VRE on admission and twice weekly. Active surveillance was undertaken for VRE infections and colonizations, and for bloodstream infections (BSI) with any pathogen. Intervention in this before-after study comprised of standardized octenidine-based bathing. Distinct subgroups of VRE colonizations or infections were defined and used for statistical analysis of frequency, prevalence and incidence density. In the pre-intervention period (January 2012 to April 2013), the admission prevalence of VRE was 4/100 patients and the mean incidence density of nosocomial cases was 7.55/1000 patient-days (PD). Pulsed-field gel electrophoresis analysis revealed prevalence of three vanA and two vanB clusters. In the post-intervention period (August 2013 to March 2014), the admission prevalence of VRE was 2.41/100 patients and the mean incidence density of nosocomial cases was 2.61/1000 PD [P=0.001 (pre- vs post-intervention)]. Thirteen nosocomial VRE infections were identified in the pre-intervention period, compared with one nosocomial VRE infection in the post-intervention period. Incidence densities of BSI pre- and post-intervention were 2.98 and 2.06/1000 PD (P=0.15), respectively. The epidemiology of emerging VRE appeared as a complex mix of admitted cases and transmissions in small clusters, challenging infection control measures. The implementation of universal octenidine-based bathing combined with a standardized washing regime led to a significant reduction in nosocomial VRE.

Molecular characterization of vancomycin-resistant Enterococcus faecium strains isolated from carriage and clinical samples in a tertiary hospital, Turkey

This study aimed to determine the presence of vancomycin resistance (vanA and vanB) and virulence genes (esp, asa1, gelE, ace, hyl, cylA, cpd and ebpA) in vancomycin-resistant Enterococcus faecium (VREfm) strains and to analyse the clonal relationships among the strains. E. faecium strains were identified from rectal and clinical specimens by biochemical tests and the API-20 Strep kit. Susceptibility testing was performed using disc-diffusion and broth-dilution methods. PFGE was used for molecular typing of the VREfm strains. The vancomycin resistance and virulence genes were amplified by two-step multiplex PCR. All 55 VREfm isolates were resistant to penicillin G, ampicillin and high-level gentamicin but were susceptible to quinupristin/dalfopristin and linezolid. Multiplex PCR analysis indicated that all isolates harboured vanA and that 41 (75 %) were positive for virulence genes. The esp gene was the most common virulence factor and was detected in nine (41 %) invasive and 32 (96.7 %) non-invasive isolates. Multiple virulence genes were observed only in two non-invasive isolates; one harboured esp and ebpA and the other harboured esp, ebpA, asa1, gelE and cpd. PFGE typing yielded 16 different types, seven of which were clusters with two to 14 strains each. The clustering rates of the rectal swab, blood and urine isolates were 72.7 %, 61.5 % and 87.5 %, respectively. The genetic similarity observed among the VREfm isolates indicated cross-transmission in the hospital. Further studies on the virulence factors present in the strains might provide insight into the acquisition of these traits and their contribution to increased prevalence of VREfm.

Vancomycin resistant Enterococcus spp (VRE): Follow up during 9 years in a Tertiary Teaching Hospital in Southern Brazil

Introduction: Infection with vancomycin-resistant Enterococcus spp (VRE) has been a worldwide problem since mid 1980's and, in Brazil, since 1996. This study was conducted to evaluate the experience with VRE in our institution. Methods: A prospective cohort study from 2000 to 2009 was conducted at Hospital Sao Lucas da PUCRS. All hospitalized patients with VRE positive culture were included and followed from their diagnosis until they were negative for VRE or their discharge. Only the first admission for each VRE positive patient was included. Pulsed field gel electrophoresis (PFGE) was performed to determine how VRE had spread. Results: A total of 315 cases of VRE were identified, 224 of which were isolated from rectal swabs. Vancomycin-resistant/ampicilin susceptible Enterococcus faecalis were identified in 312 isolates. PFGE was performed in 47 VRE isolates that presented an indistinguishable migratory profile. The median length of hospital stay and length of stay before VRE isolation were 46 days and 21 days, respectively; 52% of the patients were aged 60 and above. The annual distribution of the new VRE cases showed a clear decrease from 2000 to 2009. Discussion: This study shows a substantial VRE colonization (71%) with a homogenous pattern that emphasizes its transversal spread. Predominance of E. faecalis differs from the literature which largely describes a higher prevalence of vancomycin-resistant Enterococcus faecium . The follow up of VRE during 9 years in our institution highlighted the importance of continuous surveillance to prevent outbreaks in our hospital.

Vancomycin-resistant Enterococcus

The reported prevalence of vancomycin-resistant Enterococcus faecium (VRE) in Switzerland for the years 2008-2010 has been low at <5%. At the University Hospital Zurich, 17 cases of VRE were detected between 28 December 2009 and 15 February 2010. Nine cases were diagnosed clinically; eight cases were detected by rectal screening. The centre of the outbreak was the cardiac surgery department. Four patients suffered from VRE-infections; four patients died. In order to investigate and contain the outbreak, the following measures were taken: prevalence surveys using weekly rectal screening, environmental screening; selective enrichment culturing; pulsed field gel electrophoresis (PFGE) for clonal typing and polymerase chain reaction-analysis (PCR) for resistance determinants and virulence factors detection. Contact isolation in single rooms and enhanced surface-disinfection methods were implemented. Ward nurses were assigned as link nurses. Regular teaching was carried out aiming to improve hand disinfection among healthcare workers. PFGE revealed two main pulsotypes each including seven patients. Five minor pulsotypes originated from three additional patients and one sample collected from a keyboard. Two of three patients with minor pulsotypes had been treated abroad. PCR-analysis identified vanB resistance-genotypes with exception of one vanA resistance-genotype. The outbreak was associated with environmental contamination and insufficient compliance with hand-hygiene. Enhanced awareness and infection control measures resulted in termination of the VRE outbreak within eight weeks. The complexity of the outbreak with several clones in parallel suggests a higher baseline prevalence of VRE in Switzerland than previous surveillance data indicate.

Molecular epidemiology of urinary tract isolates of vancomycin-resistant Enterococcus faecium from North America

Vancomycin-resistant Enterococcus faecium (VRE) are a common cause of nosocomial infections and are important agents of gastrointestinal colonisation. As the prevalence of VRE in hospitalised patients continues to increase, implementation of appropriate infection control measures requires routine surveillance of VRE transmission patterns. The purpose of the present study was to investigate the molecular epidemiology of VRE isolates within the USA and Canada. Two hundred and eighty-three urinary tract isolates of VRE were collected in the year 2000 from ten Canadian hospitals and 28 US tertiary care medical centres representing seven of the nine geographic regions of the United States Bureau of the Census. The in vitro activity of vancomycin, teicoplanin and nine comparators was determined by broth microdilution. The genetic relatedness among isolates was evaluated by pulsed-field gel electrophoresis (PFGE). Resistance rates (intermediate and resistant) were 100% for vancomycin and 78.7% for teicoplanin. Resistance was lowest with linezolid, chloramphenicol and nitrofurantoin at 0.3%, 0.3% and 0.5%, respectively. PFGE revealed that genetic heterogeneity amongst isolates from each of the medical centres varied considerably. Despite some intracentre and intercentre VRE dissemination, the present study found no evidence for the emergence of a dominant clonal strain. This suggests that the spread of VRE within North America is a complex process involving both the horizontal transfer of glycopeptide resistance determinants and polyclonal dissemination.

Activity of daptomycin against susceptible and multidrug-resistant Gram-positive pathogens collected in the SECURE study (Europe) during 2000-2001.

Antibiotic resistance was prevalent in Gram-positive pathogens collected from 40 sites in 15 European countries during 2000-2001. Among Staphylococcus aureus, 27.3% of all isolates submitted were resistant to oxacillin and ranged from 0% of isolates from the Netherlands to 36.9% of isolates from Portugal. The overall prevalence of vancomycin-resistant Enterococcus faecium was 25.1%, with Italy submitting the largest percentage of resistant isolates (60.6%). For Streptococcus pneumoniae, 9.4% of all isolates collected were resistant to penicillin with variation by country from 0% in the Netherlands to 20.7% in Portugal. Multidrug resistance (MDR), defined as concurrent resistance to three or more antimicrobials of different chemical classes, was observed in 24.6% of S. aureus, 19.6% of E. faecium and 3.6% of S. pneumoniae. The directed spectrum agents daptomycin, linezolid and quinupristin-dalfopristin were active in vitro against all isolates regardless of their resistance to other agents. Daptomycin and quinupristin-dalfopristin (MIC(90)s 0.5 mg/L) were equally active against oxacillin-resistant S. aureus compared with linezolid (MIC(90) 2 mg/L). The activities of daptomycin, quinupristin-dalfopristin and linezolid were not affected by resistance to vancomycin in E. faecium (MIC(90)s of 4, 2 and 2 mg/L, respectively). Daptomycin was more active against penicillin-resistant S. pneumoniae (MIC(90) 0.25 mg/L) than was quinupristin-dalfopristin (MIC(90) 0.5 mg/L) or linezolid (MIC(90) 2 mg/L). Daptomycin was highly active against clinically important Gram-positive pathogens, including those that were multiply resistant to currently available agents. The results of this study provide a benchmark of the activity of daptomycin against contemporary European isolates and will serve as a baseline to monitor future changes in the susceptibility of these organisms to daptomycin.

Prevalence of vancomycin-resistant Enterococcusfaecium (VREF) in pig faeces from slaughterhouses in Spain

A study to estimate the prevalence of vancomycin-resistant Enterococcus faecium in faecal samples from pigs at slaughterhouses in Spain was carried out between November 1998 and January 1999 with 900 samples taken from four abattoirs representing 9.7% of all pig slaughtered in 1998. Using a selective enrichment broth with vancomycin (8μg/ml), 64 samples (7.1%; 95% CI: 5.5, 9.0%) had E. faecium vancomycin-resistant strains that showed minimal inhibitory concentrations of 256μg/ml (62 strains) and 512μg/ml (two strains). Results by farm showed that 43 of the 240 pig farms represented in the sampling had at least one faecal sample with vancomycin-resistant E. faecium.