Cumulative incidence of vancomycin-resistant Enterococcus faecium detection by patient characteristics or possible exposures: Prioritization of patients for active screening culture.

OBJECTIVES: The target population for active surveillance culture (ASC) of vancomycin-resistant Enterococcus species (VRE) by stool or rectal swabs has not been fully determined during VRE outbreaks in healthcare settings in non-VRE endemic situation. We evaluated cumulative incidences of VRE detection during a vancomycin-resistant Enterococcus faecium outbreak to determine reasonable target populations for ASC. METHODS: Cases included inpatients whose first VRE-positive sample was obtained at Shizuoka General Hospital between February 2022 and January 2023, during which we conducted admission screening for possible high-risk patients, biweekly screening of all inpatients, admission and discharge screening in the high-care unit, and screening of contacts in each ward by using stool or rectal samples. We calculated cumulative incidences of VRE detection for those screened by patient characteristics or possible exposure. FINDINGS: Among 60 cases identified, 55 (92%) were by ASC. Cumulative incidence was higher for contacts (6.4%, 15/234) than for those identified by other screening methods (0.5%, 40/8565). Among the patients identified through admission screening, those previously hospitalized in areas of reported VRE outbreaks had the highest cumulative incidence (6.6%, 5/78) followed by patients requiring toilet assistance (3.7%, 6/161). A bundle approach including ASC and prompt contact precautions by the hospital infection control team, local public health centre, and local and national infection control experts helped terminate the outbreak in seven months. CONCLUSION: Patients with contacts, prior hospitalization in areas with known VRE outbreaks, and who need toilet assistance appear to be high-risk populations for VRE detection and are candidates for ASC.

Investigation of the Impact of Antibiotic Administration on the Preterm Infants' Gut Microbiome Using Next-Generation Sequencing-Based 16S rRNA Gene Analysis.

Background: The human gut microbiota is an extensive population of microorganisms, and it shows significant variations between periods of optimal health and periods of illness. Vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae (CRKP) are both pathogenic agents (BPAs) that can colonize in the gut after dysbiosis of microbiotal composition following antibiotic treatment. Methods: This study aimed to investigate the impact of antibiotics on the microbiotal composition of the gut. For this purpose, the first pass meconiums of 20 patients and the first rectal swabs containing BPAs of the same patients after antibiotic treatment were studied using next-generation sequencing-based 16S rRNA gene analysis. The V1-V9 region of 16S rRNA was sequenced with Oxford Nanopore. Results: Twenty-five phyla were detected in the meconiums, and 12 of them were absent after antibiotic treatment. The four most prevalent phyla in meconiums were Bacillota, Pseudomonadota, Bacteroidota, and Actinomycetota. Only the relative abundance of Pseudomonadota was increased, while a significant decrease was observed in the other three phyla (p < 0.05). A significant decrease was observed in alpha-diversity in rectal swabs containing BPAs versus meconiums (p = 0.00408), whereas an increased variance was observed in beta-diversity in all samples (p < 0.05). As a result of a LEfSe analysis, Pseudomonadota was found to have a higher relative abundance in rectal swabs, and Bacillota was significantly higher in the meconiums of the twins. Conclusions: Our study strongly verified the relationship between the administration of antibiotics, dysbiosis, and colonization of BPAs in the infants' gut microbiota. Further research would be beneficial and needed, comprising the natural development process of the infants' gut microbiota.

Cytotoxic Activity of Vancomycin-Resistant Enterococci Isolated from Hospitalised Patients.

Vancomycin-resistant enterococci (VRE) are considered one of the main nosocomial pathogens due to their increasing antibiotic resistance and ability to cause life-threatening infections in humans. This study included VRE isolates obtained from various specimens including urine, blood, faeces, wounds, sputum, and oral cavity wash. Of the 37 strains, 30 (81.1%) and 7 (18.9%) were identified by MALDI TOF as Enterococcus faecium and Enterococcus faecalis, respectively. The clinical vancomycin-resistant enterococci exhibited multi-drug resistance (MDR). Apart from vancomycin, the enterococci exhibited resistance to penicillins (89.1 to 100%), fluoroquinolones (100%), rifampicin (86.5%), tetracycline (27%), aminoglycosides (56.8 to 86.5%), quinupristin-dalfopristin (35.1%), and chloramphenicol (10.8%). Moreover, resistance to linezolid and tigecycline emerged among the tested vancomycin-resistant enterococci. The analysis of aminoglycoside modifying enzyme (AME) genes showed the presence of bifunctional aac(6')-Ie-aph(2″)-Ia genes contributed to high-level aminoglycoside resistance (HLAR) in the E. faecalis and E. faecium isolates. The other AME gene, i.e., aph(3')-IIIa, was also found in the VRE isolates. All strains carried the vanA gene. Enterococci from colonised gastrointestinal tracts (1/2.7%) and from infection (6/16.2%) showed cytotoxic activity against the human epithelial cell line HEp-2.

Development of a One-Step Multiplex qPCR Assay for Detection of Methicillin and Vancomycin Drug Resistance Genes in Antibiotic-Resistant Bacteria.

The most common antibiotic-resistant bacteria in Korea are methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Pathogen identification in clinical laboratories can be divided into traditional phenotype- and genotype-based methods, both of which are complementary to each other. The genotype-based method using multiplex real-time polymerase chain reaction (PCR) is a rapid and accurate technique that analyzes material at the genetic level by targeting genes simultaneously. Accordingly, we aimed to develop a rapid method for studying the genetic characteristics of antibiotic-resistant bacteria and to provide an experimental guide for the efficient antibiotic resistance gene analysis of mecA detection for MRSA and vanA or vanB detection for VRE using a one-step multiplex qPCR assay at an early stage of infection. As a result, the sensitivity and specificity of the mecA gene for clinical S. aureus isolates, including MRSA and methicillin-susceptible S. aureus, were 97.44% (95% CI, 86.82-99.87%) and 96.15% (95% CI, 87.02-99.32%), respectively. The receiver operating characteristic area under the curve for the diagnosis of MRSA was 0.9798 (*** p < 0.0001). Therefore, the molecular diagnostic method using this newly developed one-step multiplex qPCR assay can provide accurate and rapid results for the treatment of patients with MRSA and VRE infections.

Presence of multiple van genes among glycopeptide non-susceptible Staphylococcus aureus exhibiting in vitro MIC creep phenomenon: A study from north-east India.

Background & objectives The global prevalence of vancomycin-resistant Staphylococcus aureus (VRSA) has increased two fold since 2010, accounting for 2.4 per cent of S. aureus infections. The emerging hVISA isolates and their increasing trends pose a serious therapeutic challenge. The present study investigated in vitro vancomycin and teicoplanin minimum inhibitory concentration (MIC) creep in S. aureus and assessed their revertants. Methods A total of 845 isolates were collected for this study, and 246 were confirmed as S. aureus. Molecular characterization of vancomycin resistance was carried out by PCR assay targeting genes types viz: vanA, vanB, vanC, vanC2/C3, vanD, vanE, and vanG. MIC was determined for vancomycin and teicoplanin by agar dilution method. MIC creep and revertant analysis were done by broth dilution method in the presence and absence of antibiotics. Results PCR assay confirmed 12 isolates were harboured vanA, followed by vanD (n=8) and vanB (n=7). The study showed 69 isolates were screened positive for glycopeptide non-susceptibility. While analyzing vancomycin MIC creep, four isolates showed a significant increase in MIC, whereas no creep phenomenon was observed for the rest. In the case of teicoplanin, seven isolates showed the MIC creep phenomenon. Revertant analysis of all the isolates that showed MIC creep phenomenon for vancomycin and teicoplanin reverted to their original MIC when the antibiotic pressure was withdrawn. Interpretation & conclusions In the present study setting, glycopeptide non-susceptibility was found in eight per cent of the isolates, and the present study found the occurrence of multiple van genes from isolates calculated from a single study center will impose a serious challenge in infection control and antibiotic policy. This study also underscores that heterogenic resistant isolates, upon exposure to vancomycin and teicoplanin at a minimum level, exhibited an increase in MIC, which will impact individuals receiving glycopeptide therapy.

Global landscape of vancomycin-resistant enterococci in hematopoietic stem-cell transplantation patients: a systematic review and meta-analysis.

BACKGROUND: One of the main risks of infection after hematopoietic stem cell transplantation (HSCT) is infection by gram-positive bacteria, including vancomycin-resistant enterococci (VRE). Based on the format of a global review and meta-analysis study, this study aims to investigate the incidence of VRE bloodstream infection (BSI) after HSCT in colonized individuals. METHODS: The keywords of the systematic search included vancomycin-resistant enterococci and HSCT. These words were searched in Google Scholar, PubMed/Medline, Scopus, and Web of Science databases from January 1, 2000, to March 1, 2024. Studies that reported the prevalence of vancomycin-resistant enterococci in patients undergoing HSCT were included. The random effects model was used for the meta-analyses. Investigations were conducted according to PRISMA guidelines, and the protocol was registered in PROSPERO: CRD42024543491. RESULTS: Out of 1100 screened papers, 28 were eligible. The random effects model was established to analyze the incidence of VRE BSI after HSCT. The pooled prevalence of co-infection for Allo-HSCT recipients was 3.023 (95% CI, Z-value = -3.5, p-value < 0.0001), and this value for Auto-HSCT recipients was 11.89 (95% CI, Z-value = -2.923, p-value < 0.001). These results showed that the rate of BSI due to vancomycin-resistant enterococcus in Auto-HSCT recipients is higher than Allo-HSCT. CONCLUSIONS: The prevalence of vancomycin-resistant enterococci in Auto-HSCT recipients is higher than that of Allo-HSCT, possibly due to colonization of the intestines of these people with vancomycin-resistant enterococci before transplantation. VRE Colonization before transplantation increases the likelihood of post-transplant VRE BSI and other bacterial infections, including Gram-negative. The strains should be analyzed by sequencing before and after HSCT for a more detailed investigation.

Management of vancomycin-resistant Enterococcus faecium in Dutch health care institutes: a nation-wide survey.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) is an opportunistic pathogen, which can cause outbreaks in hospitals. In the Netherlands, several national guidelines and guidance documents on different aspects of VREfm-management are available. Most available guidelines are written towards the hospital setting and only few on long-term care facilities (LTCFs). Moreover, not all aspects of VREfm-management are covered, recommendations differ and the level of compliance to these guidelines is unknown. The aim of this study was to get insight into the routine VREfm-policies in Dutch healthcare facilities with regard to screening, diagnostics and infection control measures. MATERIALS AND METHODS: Online questionnaires were sent to representatives of Dutch hospitals and long-term care facilities (LTCFs). The questionnaire included questions regarding the definition of VRE, screening, diagnostics, patient isolation, cleaning procedures, VREfm-clearance and VREfm-outbreaks. RESULTS: The questionnaire was completed by 61 hospitals with a response rate of 84.1% and 57 LTCFs, mostly nursing homes. Most hospitals reported VRE-outbreaks in the previous decade, whereas only one LTCFs reported an outbreak. Of the hospitals, 87% perform VREfm-screening versus 50% of the LTCFs. VRE-positive patients are isolated in 98% of hospitals and 83% of LTCFs. Protocols regarding how to unlabel VRE-positive patients are in place in 84% of the hospitals and in 51% of LTCFs. The details of these measures differ substantially between healthcare facilities. CONCLUSION: This study has shown that most hospitals and some LTCFs in the Netherlands have standard procedures for VREfm-management to some level, although the comprehensiveness and details of the measures differ per hospital. More uniform policies would improve comparability of VREfm data on a regional/national level.

Evaluation of Screening Results for Vancomycin-Resistant Enterococci: Three-Year Surveillance.

Background: Enterococci are facultative anaerobic, binary, or chained Gram-positive cocci. The gastrointestinal colonization of hospitalized patients is the most important reservoir of vancomycin-resistant enterococci. We aimed to evaluate retrospectively the screening results of vancomycin-resistant enterococci, studied by the simultaneous (real-time) polymerase chain reaction method on rectal swabs of adult and pediatric patients hospitalized in our hospital in 2019-2021. Methods: Adult and pediatric patients were included in our study between Jan 2019 and Dec 2021. The results of vancomycin-resistant enterococci, studied with the real-time polymerase chain reaction method from rectal swabs sent from intensive care units and services, were analyzed retrospectively. Isolation of the samples was performed using the Fluorion VRE QLP 1.0 real-time polymerase chain reaction kit (Iontek, Turkey), and detection was performed with the Fluorion Detection System (Iontek, Turkey) real-time polymerase chain reaction device. Results: Overall, 31,725 patients were included in our study. When evaluated in order of years, in 2019, 379 (7%) of 5,389 adults, 322 (7.4%) of 4,003 children, 234 (5.5%) of 4,185 adults in 2020, 157 (2.4%) of 6,499 children, and in 2021, vancomycin-resistant enterococci were detected in 469 (7.5%) of 6,232 adults and 224 (4.1%) of 5,417 children. Conclusion: The prevalence of vancomycin-resistant enterococci is greater in adults, particularly in intensive care units, compared to children. Infection control precautions and training be augmented in high-risk clinics, while the unnecessary utilization of glycopeptides should be limited.

Potential Use of Fourier-Transform Infrared Spectroscopy as a Rapid Screening Tool for Investigating Nosocomial Outbreaks of ST-80 Vancomycin-Resistant Enterococcus faecium.

Core genome single-nucleotide polymorphism phylogeny was used to characterise a nosocomial outbreak caused by ST-80 Vancomycin-resistant Enterococcus faecium (VREf). It identified 22 of 25 epidemiologically related isolates as belonging to an outbreak cluster. The use of Fourier-transform infrared (FT-IR) spectroscopy with a cluster-defining cut-off of 0.071 resulted in the correct classification of 21 of 22 phylogenetically related isolates in a single cluster. It successfully distinguished three phylogenetically unrelated isolates from the outbreak cluster, along with five ST-80 unrelated control isolates, and five isolates from a previous outbreak in May 2023, yielding only one mischaracterised environmental isolate. These findings support the potential use of FT-IR spectroscopy as a rapid screening tool to assist outbreak investigations. Notably, this study is the first to focus on the performance of FT-IR spectroscopy in the epidemiological analysis of VREf isolates with the same sequence type.

AVR/I/SSAPDB: a comprehensive & specialised knowledgebase of antimicrobial peptides to combat VRSA, VISA, and VSSA.

The rise of multi-drug resistant (MDR) bacteria, especially strains of Staphylococcus aureus like Vancomycin-resistant S. aureus (VRSA), Vancomycin-intermediate S. aureus (VISA), and Vancomycin-susceptible S. aureus (VSSA), poses a severe threat to global health. This situation underscores the urgent need for novel antimicrobial agents to combat these resistant strains effectively. Here, we are introducing the Anti-Vancomycin-Resistant/Intermediate/Susceptible Staphylococcus aureus Peptide Database (AVR/I/SSAPDB), a manually curated comprehensive and specialised knowledgebase dedicated to antimicrobial peptides (AMPs) that target VRSA, VISA, and VSSA with clinical and non-clinical significance. Our database sources data from PubMed, cataloging 491 experimentally validated AMPs with detailed annotations on peptides, activity, and cross-references to external databases like PubMed, UniProt, PDB, and DrugBank. AVR/I/SSAPDB offers a user-friendly interface with simple to advanced and list-based search capabilities, enabling researchers to explore AMPs against VRSA, VISA, and VSSA. We are hoping that this resource will be helpful to the scientific community in developing targeted peptide-based therapeutics, providing a crucial tool for combating VRSA, VISA, and VSSA, and addressing a major public health concern. AVR/I/SSAPDB is freely accessible via any web-browser at URL: https://bblserver.org.in/avrissa/ .

Management of vancomycin-resistant Enterococci and daptomycin-resistant Enterococci infections in liver transplant recipients in a single academic center.

INTRODUCTION: Vancomycin-resistant Enterococci (VRE) infections cause significant morbidity and mortality in liver transplant (LT) recipients. Management is challenging, especially in the setting of daptomycin resistance (DR). METHODS: Single-center retrospective review of patients who underwent LT between January 1, 2020, and December 31, 2022, and developed VRE infections. Descriptive statistics were used and Kaplan-Meier curves estimated freedom from treatment failure and survival. RESULTS: Forty-two patients (median age 58; 64% female; 67% white) were included. Alcohol-related cirrhosis (48%) and metabolic dysfunction-associated steatohepatitis (31%) were the most common indications for LT, and most were from deceased donors (86%). VRE infection occurred at a median of 21 days after LT, and 16% had known prior VRE colonization. Common infection sites were blood (45%, n = 19), intraabdominal (36%, n = 15), and urine (36%, n = 15). Most were initially treated with daptomycin alone (64%) or in combination with other agents (21%); 7% received linezolid alone. Twelve (29%) developed breakthrough infections during treatment and 11 (26%) had recurrent infections after discontinuation of treatment. All-cause mortality was 36% (n = 15) at a median of 90 days after VRE infection diagnosis and was nearly twice as high in patients with DR (63%). CONCLUSION: VRE infection in LT recipients relapsed or recurred in over 25%. Mortality was high, especially in cases with DR. More data is needed to establish an optimal treatment approach, particularly for relapse and DR.

Real-World Clinical Characteristics and Outcomes with Daptomycin Use in Pediatric Patients: A Retrospective Case Series.

INTRODUCTION: Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. METHODS: This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. RESULTS: Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4-16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6-10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8-18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). CONCLUSION: Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes.

Development and application of a rapid visual detection technique for VanA gene in vancomycin-resistant Enterococcus faecium.

The objective of this study was to establish a rapid visual diagnosis method for vancomycin-resistant Enterococcus faecium (VREFm) based on multienzyme isothermal rapid amplification (MIRA) combined with lateral flow strips (LFSs). The MIRA primers and probes were specifically designed to maintain the sequence of the VanA gene of VREFm. We optimized the reaction time and temperature and thoroughly assessed the specificity and sensitivity of the MIRA-LFS system. We also compared the MIRA-LFS method with the polymerase chain reaction (PCR) assay and the disc diffusion method. We then evaluated the MIRA-LFS assay for consistency testing and clinical application. The MIRA-LFS technique completed the amplification process within 30 min, and the results were observed on LFS. The method demonstrated high sensitivity, with a minimum detection limit of 1.066 CFU/µL for VREFm and exhibited specificity without cross-reactivity with other pathogenic bacteria. When applied to the detection of clinical samples, the method exhibited consistency with the PCR and agar dilution methods. The combined use of MIRA and LFS in this study facilitates simplifying the workflow for detecting VREFm, which is of great significance for rapidly detecting the enterococcal infections and preventing and controlling the nosocomial infections. IMPORTANCE: One of the key approaches to treating and controlling vancomycin-resistant Enterococcus faecium (VREFm) is an accurate and rapid diagnosis. To achieve this goal, a simple and rapid method must be constructed for immediate detection in the field. Multienzyme isothermal rapid amplification (MIRA) is an isothermal rapid amplification method that allows amplification reactions to be completed under room temperature conditions. When combined with lateral flow strips (LFSs), MIRA-LFS enables the rapid detection of pathogenic microorganisms. However, the MIRA method often produces false signals. These false signals are eliminated by using base mismatches introduced in primers and probes. The MIRA-LFS system was constructed with high specificity and sensitivity for the detection of VREfm, without the limitation of sophisticated instruments. This enables the prompt formulation of diagnostic and therapeutic decisions.

Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice.

Background: The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear. Methods: Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant Enterococcus (VRE) resistant to each of the antibioics or carbapenemase-producing Klebsiella pneumoniae 1 day after the final treatment dose. The concentrations of VRE or K. pneumoniae in stool were measured on days 1, 3, 6, and 15 after challenge. Results: Control mice had transient low levels of VRE or K. pneumoniae (<3 log10 CFU/g) detected in stool with negative cultures on days 6 and 15 after challenge. In comparison to control mice, each of the antibiotics promoted establishment of high-density colonization with VRE (mean concentration, >8 log10 CFU/g of stool on day 1 after challenge) that persisted at >4 log10 CFU/g of stool through day 15 (P<0.01). In comparison to control mice, meropenem/vaborbactam and ceftaroline promoted high-density colonization with K. pneumoniae (peak concentration, >8 log10 CFU/g of stool) (P<0.01), ceftolozane/tazobactam promoted colonization to a lesser degree (peak concentration, >5 log10 CFU/g of stool), and ceftazidime/avibactam did not promote colonization (P>0.05). Conclusions: Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2018-2022.

Background: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) continue to contribute to excess morbidity and mortality among Canadians. Objective: This report describes epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2018 to 2022 (Candida auris, 2012-2022) using surveillance and laboratory data submitted by hospitals to the Canadian Nosocomial Infection Surveillance Program (CNISP) and by provincial and territorial laboratories to the National Microbiology Laboratory. Methods: Data collected from 88 Canadian sentinel acute care hospitals between January 1, 2018, and December 31, 2022, for Clostridioides difficile infections (CDIs), carbapenemase-producing Enterobacterales (CPE) infections, methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) and vancomycin-resistant Enterococcus (VRE) BSIs. Candida auris (C. auris) surveillance was initiated in 2019 by CNISP and in 2017 (retrospectively to 2012) by the National Microbiology Laboratory. Trend analysis for case counts, rates, outcomes, molecular characterization and AMR profiles are presented. Results: From 2018 to 2022, decreased rates per 10,000 patient days were observed for CDIs (7% decrease; 5.42-5.02) and MRSA BSIs (2.9% decrease; 1.04-1.01). Infection rates for VRE BSIs increased by 5.9% (0.34-0.36). Infection rates for CPE remained low but increased by 133% (0.06-0.14). Forty-three C. auris isolates were identified in Canada from 2012 to 2022, with the majority in Western and Central Canada (98%). Conclusion: From 2018 to 2022, the incidence of MRSA BSIs and CDIs decreased and VRE BSI and CPE infections increased in the Canadian acute care hospitals participating in a national sentinel network (CNISP). Few C. auris isolates were identified from 2012 to 2022. Reporting standardized surveillance data to inform the application of infection prevention and control practices in acute care hospitals is critical to help decrease the burden of HAIs and AMR in Canada.

Vancomycin-resistant Enterococcus faecium bacteremia in End-Stage Renal Disease (ESRD) and Focal Segmental Glomerulosclerosis (FSGS) patient under hemodialysis.

Background: Today, one of the important challenges related to the emergence of antibiotic resistance among hospital-acquired infections is Vancomycin-Resistant Enterococci (VRE). The identification of the hospital transfer pattern and accurate laboratory diagnosis can be effective in preventing or selecting the appropriate antibiotics for the treatment of these types of infections, especially in hemodialysis patients. Case report: This report discusses the hospitalization of a 2.5-year-old boy with End-Stage Renal Disease (ESRD) and Focal Segmental Glomerulosclerosis (FSGS) at a nephrology center in a tertiary hospital. The patient received hemodialysis treatment, followed by an abdominal tap, which revealed an infection. Peritoneal and blood cultures were conducted using the BACT/ALERT®3D instrument, and the results indicated a bacterial infection during the hospital stay. Further analysis confirmed that the infection was caused by enterococci, and susceptibility testing revealed that the isolated strain was resistant to vancomycin. Fortunately, the enterococci infection responded well to linezolid antibiotic treatment, administered at a dose of 600 mg PO/IV q12hr for 14 days. Conclusions: This report highlights the importance of healthcare workers being aware of the transmission routes of VRE among patients. It emphasizes the need for appropriate hand hygiene, sterility of extracorporeal devices, and proper catheter care in medical centers.

6-Methoxyldihydrochelerythrine Chloride Inhibiting Intra and Extracellular Drug-Resistant Bacteria.

Vancomycin-resistant enterococcus (VRE) is a major nosocomial pathogen that exhibits enhanced infectivity due to its robust virulence and biofilm-forming capabilities. In this study, 6-methoxyldihydrochelerythrine chloride (6-MDC) inhibited the growth of exponential-phase VRE and restored VRE's sensitivity to vancomycin. 6-MDC predominantly suppressed the de novo biosynthetic pathway of pyrimidine and purine in VRE by the RNA-Seq analysis, resulting in obstructed DNA synthesis, which subsequently weakened bacterial virulence and impeded intracellular survival. Furthermore, 6-MDC inhibited biofilm formation, eradicated established biofilms, reduced virulence, and enhanced the host immune response to prevent intracellular survival and replication of VRE. Finally, 6-MDC reduced the VRE load in peritoneal fluid and cells significantly in a murine peritoneal infection model. This paper provides insight into the potential antimicrobial target of benzophenanthridine alkaloids for the first time.

Persistence of Daptomycin-Resistant and Vancomycin-Resistant Enterococci in Hospitalized Patients with Underlying Malignancies: A 7-Year Follow-Up Study.

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified in 2012. Eleven of twenty-eight patients with DR-VRE were never exposed to daptomycin, suggesting horizontal transmission. Fifteen of the twenty-eight patients with DR-VRE died within 30 days of positive blood cultures. Amongst those, one DR-VRE strain belonging to ST1471 had the virulence gene bopD responsible for biofilm formation. Additionally, to our knowledge, this is the first report of a DR-VRE strain belonging to ST323 in the United States. In summary, our study demonstrated the emergence and persistence of VRE strains, especially DR-VRE, in our hospital. Adding WGS to routine infection control measures may timely identify potential horizontal VRE transmission including multi-drug-resistant isolates.

Bacteriocin production facilitates nosocomial emergence of vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (VREfm) is a prevalent healthcare-acquired pathogen. Gastrointestinal colonization can lead to difficult-to-treat bloodstream infections with high mortality rates. Prior studies have investigated VREfm population structure within healthcare centers. However, little is known about how and why hospital-adapted VREfm populations change over time. We sequenced 710 healthcare-associated VREfm clinical isolates from 2017-2022 from a large tertiary care center as part of the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT) program. Although the VREfm population in our center was polyclonal, 46% of isolates formed genetically related clusters, suggesting a high transmission rate. We compared our collection to 15,631 publicly available VREfm genomes spanning 20 years. Our findings describe a drastic shift in lineage replacement within nosocomial VREfm populations at both the local and global level. Functional and genomic analysis revealed, antimicrobial peptide, bacteriocin T8 may be a driving feature of strain emergence and persistence in the hospital setting.

Clonal expansion of Tn1546-like transposon-carrying vancomycin-resistant Enterococcus faecium, a nationwide study in Taiwan, 2004-2018.

OBJECTIVES: The prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased significantly in Taiwan. We investigated the molecular epidemiology of clinical VREfm isolates to increase our understanding on their spread and changes in population structure over a 14-year span. METHODS: A total of 1113 E. faecium isolates were collected biennially from 2004 to 2018 in Taiwan. MICs were determined by broth microdilution. Whole-genome sequencing (WGS) was performed on 229 VREfm isolates to characterize their genetic environment of vancomycin resistance and wgMLST was used to investigate their clonal relationship. RESULTS: Among the 229 isolates, ST17 and ST78 predominated, especially during the later years, and their prevalences increased from 14.6% (7/48) and 25.0% (12/48) in 2004-2010 to 47.5% (87/181) and 29.8% (54/181) in 2012-2018, respectively. Four types of vanA-carrying Tn1546 variants were detected, with type 1 and type 2 predominated. Type 1 Tn1546 contained an addition of IS1251, while type 2 resembled type 1 but had an addition of IS1678. wgMLST revealed several distinct clusters of ST17 and ST78 isolates, with type 1 Tn1546-harbouring ST17-Cluster 16 being the largest and most widespread clones throughout the study years. Type 2 Tn1546-carrying ST78 became a predominant clone (Cluster 21) after 2012. Isolates within these clusters are highly similar despite being from different hospitals, regions, and study year. CONCLUSION: The increase of VREfm in Taiwan was attributed to horizontal transfer of vanA-carrying Tn1546 variants between different STs and spread of persistent clones. This study highlights the importance of integrating WGS into surveillance to combat antimicrobial resistance.