Currently, effective options are needed to fight vancomycin-resistant Enterococcus faecalis (VRE). The present study shows that combinations of phage and vancomycin are highly efficient against VRE, despite being resistant to the antibiotic. Vancomycin-phage EFLK1 (anti-E. faecalis phage) synergy was assessed against VRE planktonic and biofilm cultures. The effect of the combined treatment on VRE biofilms was determined by evaluating the viable counts and biomass and then visualized using scanning electron microscopy (SEM). The cell wall peptidoglycan was stained after phage treatment, visualized by confocal microscopy and quantified by fluorescence activated cell sorting (FACS) analysis. The combined treatment was synergistically effective compared to treatment with phage or antibiotic alone, both in planktonic and biofilm cultures. Confocal microscopy and FACS analysis showed that fluorescence intensity of phage-treated bacteria increased eight-fold, suggesting a change in the peptidoglycan of the cell wall. Our results indicate that with combined treatment, VRE strains are not more problematic than sensitive strains and thus give hope in the continuous struggle against the current emergence of multidrug resistant pathogens.

Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, there are only a few compounds capable of serving as a last resort for severe infections. Therefore, approaches to control multidrug-resistant bacteria must be implemented. Here, a strategy of reactivating the established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation to overcome the resistance of multidrug-resistant bacteria was followed. This study especially focuses on the structure-activity relationship, depending on the modification site and fatty acid chain length. The synthesized conjugates showed high antimicrobial potential on vancomycin-resistant enterococci. We were able to demonstrate that the antimicrobial activity of the vancomycin-lipopeptide conjugates depends on the chain length of the attached fatty acid. All conjugates showed good cytocompatibility in vitro and in vivo. Radiolabeling enabled the in vivo determination of pharmacokinetics in Wistar rats by molecular imaging and biodistribution studies. An improved biodistribution profile in comparison to unmodified vancomycin was observed. While vancomycin is rapidly excreted by the kidneys, the most potent conjugate shows a hepatobiliary excretion profile. In conclusion, these results demonstrate the potential of the structural modification of already established antibiotics to provide highly active compounds for tackling multidrug-resistant bacteria.

Enterococci have been isolated frequently worldwide and have difficulties in the treatment. Combination antibiotherapies have a distinct advantage over monotherapies in terms of their synergistic effect. In the study, it was aimed to investigate in vitro activity of vancomycin combined with fosfomycin against VRE strains.

Enterococci are important bacterial pathogens, and their significance is even greater in the case of vancomycin-resistant enterococci (VRE). The study analyzed the presence of VRE in the gastrointestinal tract (GIT) of hemato-oncological patients. Active screening using selective agars yielded VRE for phenotypic and genotypic analyses. Isolated strains were identified with MALDI-TOF MS, (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry) their susceptibility to antibiotics was tested, and resistance genes (vanA, vanB, vanC-1, vanC2-C3) and genes encoding virulence factors (asa1, gelE, cylA, esp, hyl) were detected. Pulsed-field gel electrophoresis was used to assess the relationship of the isolated strains. Over a period of three years, 103 VanA-type VRE were identified in 1405 hemato-oncological patients. The most frequently detected virulence factor was extracellular surface protein (84%), followed by hyaluronidase (40%). Unique restriction profiles were observed in 33% of strains; clonality was detected in 67% of isolates. The study found that 7% of hemato-oncological patients carried VRE in their GIT. In all cases, the species identified was Enterococcus faecium. No clone persisted for the entire 3-year study period. However, genetically different clusters were observed for shorter periods of time, no longer than eight months, with identical VRE spreading among patients.

Enterococci represent one of the microbial world's most challenging enigmas. Colonization of the gastrointestinal tract (GIT) of high-risk/immunocompromised patients by enterococci exhibiting resistance to vancomycin (VRE) can lead to life-threating infections, including bloodstream infections and endocarditis. Decolonization of VRE from the GIT of high-risk patients represents an alternative method to suppress the risk of the infection. It could be considered as a preventative measure to protect against VRE infections in high-risk individuals. Though multiple agents (ramoplanin and bacitracin) have been evaluated clinically, no drugs are currently approved for use in VRE decolonization of the GIT. The present study evaluates ebselen, a clinical molecule, for use as a decolonizing agent against VRE. When evaluated against a broad array of enterococcal isolates in vitro, ebselen was found to be as potent as linezolid (minimum inhibitory concentration against 90% of clinical isolates tested was 2 μg/ml). Though VRE has a remarkable ability to develop resistance to antibacterial agents, no resistance to ebselen emerged after a clinical isolate of vancomycin-resistant E. faecium was serially-passaged with ebselen for 14 days. Against VRE biofilm, a virulence factor that enables the bacteria to colonize the gut, ebselen demonstrated the ability to both inhibit biofilm formation and disrupt mature biofilm. Furthermore, in a murine VRE colonization reduction model, ebselen proved as effective as ramoplanin in reducing the bacterial shedding and burden of VRE present in the fecal content (by > 99.99%), cecum, and ileum of mice. Based on the promising results obtained, ebselen warrants further investigation as a novel decolonizing agent to quell VRE infection.

Vancomycin resistant enterococci are a frequent cause of nosocomial infections and their presence among farm animals is unwanted. Using media supplemented with vancomycin an increase in the proportion of samples from Swedish broilers positive for vancomycin resistant enterococci has been detected. The situation at farm level is largely unknown. The aims of this study were to obtain baseline knowledge about environmental contamination with vancomycin resistant enterococci in Swedish broiler production and the association between environmental contamination and colonisation of birds.

Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm.

Multidrug-resistant enterococcal pathogens, especially vancomycin-resistant enterococci (VRE), are among the pathogens that require new antibiotic innovation. The colonization of the gut represents a major pathway by which VRE can cause infection and spread to other patients. In the current study, auranofin (FDA-approved rheumatoid arthritis drug) is evaluated for its potential use as a decolonizing agent for VRE. Auranofin was found to exert potent antimicrobial activity against a wide range of enterococcal clinical isolates with a minimum inhibitory concentration of 1 μg/mL. No resistant mutants could be developed against auranofin over the course of 14 passages. Auranofin was also found to exert potent anti-biofilm activity against VRE. Auranofin was superior to linezolid, the drug of choice for VRE infection treatment, in the in vivo mouse model. Auranofin significantly reduced the VRE burden in feces, cecum, and ileum contents after 8 days of treatment. Accordingly, this study provides valuable evidence that auranofin has significant promise as a novel gastrointestinal decolonizing agent for VRE.

Vancomycin-Resistant Enterococci (VRE) are on the rise worldwide. Here, we report the first prevalence of VRE in Nigeria using systematic review and meta-analysis. International databases MedLib, PubMed, International Scientific Indexing (ISI), Web of Science, Scopus, Google Scholar, and African journals online (AJOL) were searched. Information was extracted by two independent reviewers, and results were reviewed by the third. Two reviewers independently assessed the study quality using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. OpenMeta analyst was used. The random effect was used, and publication bias was assessed using a funnel plot. Between-study heterogeneity was assessed, and the sources were analysed using the leave-one-out meta-analysis, subgroup analysis, and meta-regression. Nineteen studies met the eligibility criteria and were added to the final meta-analysis, and the study period was from 2009-2018. Of the 2552 isolates tested, 349 were VRE, and E. faecalis was reported the most. The pooled prevalence of VRE in Nigeria was estimated at 25.3% (95% CI; 19.8-30.8%; I2 = 96.26%; p < 0.001). Between-study variability was high (t2 = 0.011; heterogeneity I2 = 96.26% with heterogeneity chi-square (Q) = 480.667, degrees of freedom (df) = 18, and p = 0.001). The funnel plot showed no publication bias, and the leave-one-out forest plot did not affect the pooled prevalence. The South-East region had a moderate heterogeneity though not significant (I2 = 51.15%, p = 0.129). Meta-regression showed that all the variables listed contributed to the heterogeneity except for the animal isolate source (p = 0.188) and studies that were done in 2013 (p = 0.219). Adherence to proper and accurate antimicrobial usage, comprehensive testing, and continuous surveillance of VRE are required.

Vancomycin-resistant enterococci (VRE) are prominent causes of nosocomial infections. Japanese traditional (Kampo) medicine promotes intestinal immunity and protects against bacterial infections. We assessed potential differences in the clinical course of VRE-positive patients, based on their characteristics and treatment with Kampo medicines. This retrospective observational study collected data from VRE-positive patients from August 2018 to July 2019 at a tertiary-care hospital in Japan. The data of 122 consecutive VRE-positive inpatients were analyzed. Sixty-nine patients were treated with probiotics, among whom, 18 were further treated with Kampo medicines. Twenty-six of the 122 patients subsequently died. In univariate analyses, subsequent VRE negative conversion significantly reduced the mortality of VRE-detected patients (p = .0003). Administration of probiotics (p = .0065) and Kampo medicines with probiotics (p = .0002), especially of the Kampo medicine hochuekkito (p = .0014), and a higher serum albumin level positively contributed to the subsequent VRE negative conversion. Multivariate analyses demonstrated that Kampo medicines and body mass index contributed to VRE negative conversion. Hochuekkito shortened the time needed for VRE negative conversion (p = 0.0485). Administration of Kampo medicines, especially of hochuekkito, in addition to probiotics in VRE patients may promote VRE negative conversion.

The emergence of vancomycin resistant Enterococci (VRE) is shortening the choices for clinical anti-infective therapy. The aim of this study was to investigate the mechanism of vancomycin resistance and evaluate the effect of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), daptomycin (DAP) alone or in combination against VRE.

Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells.

Emergence of vancomycin-resistant Enterococci (VRE) that first appeared on the stage about three decades ago is now a major concern worldwide as it has globally reached every continent. Our aim was to simply undertake a multinational study to delineate the resistance and virulence genes of clinical isolates of VRE isolates from the Caribbean. We employed both conventional (standard microbiological methods including use of E-test strips, chromogenic agar) and molecular methods (polymerase chain reactions-PCR, pulsed-field gel electrophoresis-PFGE and multilocus sequence typing-MLST) to analyze and characterize 245 Enterococci species and 77 VRE isolates from twelve hospitals from eight countries in the Caribbean. The PCR confirmed and demonstrated the resistance and virulence genes (vanA and esp) among all confirmed VRE isolates. The PFGE delineated clonally related isolates from patients from the same country and other countries in the region. The main sequence types of the VRE isolates from the region included STs 412, 750, 203, 736 and 18, all from the common ancestor for clonal complex 17 (CC17). Despite this common ancestor and association of outbreaks of this lineage clones, there has been no reports of outbreaks of infection by VRE in several hospitals in the Caribbean.

Food-producing animals may be a reservoir of vancomycin-resistant enterococci (VRE), potentially posing a threat to animal and public health. The aims of this study were to estimate the faecal carriage of VRE among healthy cattle (n = 362), pigs (n = 350), sheep (n = 218), and poultry (n = 102 flocks) in Switzerland, and to characterise phenotypic and genotypic traits of the isolates. VRE were isolated from caecum content of six bovine, and 12 porcine samples respectively, and from pooled faecal matter collected from 16 poultry flock samples. All isolates harboured vanA. Three different types of Tn1546-like elements carrying the vanA operon were identified. Conjugal transfer of vanA to human Enterococcus faecalis strain JH2-2 was observed for porcine isolates only. Resistance to tetracycline and erythromycin was frequent among the isolates. Our data show that VRE harbouring vanA are present in healthy food-producing animals. The vanA gene from porcine isolates was transferable to other enterococci and these isolates might play a role in the dissemination of VRE in the food production chain.

Broad-spectrum antibiotics administered to patients with severe COVID-19 pneumonia pose a risk of infection caused by Clostridioides difficile. This risk is reduced mainly by strict hygiene measures and early de-escalation of antibiotic therapy. Recently, oral vancomycin prophylaxis (OVP) has also been discussed. This retrospective study aimed to assess the prevalence of C. difficile in critical COVID-19 patients staying in an intensive care unit of a tertiary hospital department of anesthesiology, resuscitation, and intensive care from November 2020 to May 2021 and the rates of vancomycin-resistant enterococci (VRE) after the introduction of OVP and to compare the data with those from controls in the pre-pandemic period (November 2018 to May 2019). During the COVID-19 pandemic, there was a significant increase in toxigenic C. difficile rates to 12.4% of patients, as compared with 1.6% in controls. The peak rates were noted in February 2021 (25% of patients), immediately followed by initiation of OVP, changes to hygiene precautions, and more rapid de-escalation of antibiotic therapy. Subsequently, toxigenic C. difficile detection rates started to fall. There was a nonsignificant increase in VRE detected in non-gastrointestinal tract samples to 8.9% in the COVID-19 group, as compared to 5.3% in the control group. Molecular analysis confirmed mainly clonal spread of VRE.

Vancomycin-resistant Enterococci (VRE) is a global health problem and responsible for healthcare-associated infections (HAIs) in patients with prolonged hospital stay, severe underlying disease, and previous broad-spectrum antibiotic therapy. These bacteria can cross-resist and transfer drug-resistant genes to other potentially pathogenic bacteria. Therefore; this study was aimed to determine the gastrointestinal colonization rate of VRE, its antimicrobial susceptibility profile, and associated factors among hospitalized patients.

The VanRS two-component system regulates the resistance phenotype of vancomycin-resistant enterococci. VanS is a sensor histidine kinase that responds to the presence of vancomycin by autophosphorylating and subsequently transferring the phosphoryl group to the response regulator, VanR. The phosphotransfer activates VanR as a transcription factor, which initiates the expression of resistance genes. Structural information about VanS proteins has remained elusive, hindering the molecular-level understanding of their function. Here, we present X-ray crystal structures for the catalytic and ATP-binding (CA) domains of two VanS proteins, derived from vancomycin-resistant enterococci types A and C. Both proteins adopt the canonical Bergerat fold that has been observed for CA domains of other prokaryotic histidine kinases. We attempted to determine structures for the nucleotide-bound forms of both proteins; however, despite repeated efforts, these forms could not be crystallized, prompting us to measure the proteins' binding affinities for ATP. Unexpectedly, both CA domains displayed low affinities for the nucleotide, with KD values in the low millimolar range. Since these KD values are comparable to intracellular ATP concentrations, this weak substrate binding could reflect a way of regulating expression of the resistance phenotype.

The emergence of Vancomycin resistant enterococci (VRE) poses a major public health problem since it was first reported. Although the rising rates of VRE infections are being reported elsewhere in the worldwide; there is limited national pooled data in Ethiopia. Therefore, this study was aimed to estimate the pooled prevalence of VRE and antimicrobial resistance profiles of enterococci in Ethiopia.

Vancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we conducted a systematic review in the study.

The emergence of multidrug-resistant enterococci (MDRE) and particularly vancomycin-resistant enterococci (VRE) is considered a serious health problem worldwide, causing the need for new antimicrobials. The aim of this study was to discover and characterize bacteriocin against clinical isolates of MDRE and VRE. Over 10,000 bacterial isolates from water, environment and clinical samples were screened. E. faecalis strain 478 isolated from human feces produced the highest antibacterial activity against several MDRE and VRE strains. The optimum condition for bacteriocin production was cultivation in MRS broth at 37°C, pH 5-6 for 16 hours. The bacteriocin-like substance produced from E. faecalis strain EF478 was stable at 60°C for at least 1 hour and retained its antimicrobial activity after storage at -20°C for 1 year, at 4°C for 6 months, and at 25°C for 2 months. A nano-HPLC electrospray ionization multi-stage tandem mass spectrometry (nLC-ESI-MS/MS) analysis showed that the amino acid sequences of the bacteriocin-like substance was similar to serine protease of E. faecalis, gi|488296663 (NCBI database), which has never been reported as a bacteriocin. This study reported a novel bacteriocin with high antibacterial activity against VRE and MDRE.