Comparative genomics of multidrug-resistant Enterococcus spp. isolated from wastewater treatment plants.

BACKGROUND: Wastewater treatment plants (WWTPs) are considered hotspots for the environmental dissemination of antimicrobial resistance (AMR) determinants. Vancomycin-Resistant Enterococcus (VRE) are candidates for gauging the degree of AMR bacteria in wastewater. Enterococcus faecalis and Enterococcus faecium are recognized indicators of fecal contamination in water. Comparative genomics of enterococci isolated from conventional activated sludge (CAS) and biological aerated filter (BAF) WWTPs was conducted. RESULTS: VRE isolates, including E. faecalis (n = 24), E. faecium (n = 11), E. casseliflavus (n = 2) and E. gallinarum (n = 2) were selected for sequencing based on WWTP source, species and AMR phenotype. The pangenomes of E. faecium and E. faecalis were both open. The genomic fraction related to the mobilome was positively correlated with genome size in E. faecium (p < 0.001) and E. faecalis (p < 0.001) and with the number of AMR genes in E. faecium (p = 0.005). Genes conferring vancomycin resistance, including vanA and vanM (E. faecium), vanG (E. faecalis), and vanC (E. casseliflavus/E. gallinarum), were detected in 20 genomes. The most prominent functional AMR genes were efflux pumps and transporters. A minimum of 16, 6, 5 and 3 virulence genes were detected in E. faecium, E. faecalis, E. casseliflavus and E. gallinarum, respectively. Virulence genes were more common in E. faecalis and E. faecium, than E. casseliflavus and E. gallinarum. A number of mobile genetic elements were shared among species. Functional CRISPR/Cas arrays were detected in 13 E. faecalis genomes, with all but one also containing a prophage. The lack of a functional CRISPR/Cas arrays was associated with multi-drug resistance in E. faecium. Phylogenetic analysis demonstrated differential clustering of isolates based on original source but not WWTP. Genes related to phage and CRISPR/Cas arrays could potentially serve as environmental biomarkers. CONCLUSIONS: There was no discernible difference between enterococcal genomes from the CAS and BAF WWTPs. E. faecalis and E. faecium have smaller genomes and harbor more virulence, AMR, and mobile genetic elements than other Enterococcus spp.

Bloodstream Infection Due to Vancomycin-resistant Enterococcus Is Associated With Increased Mortality After Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndrome: A Multicenter, Retrospective Cohort Study.

BACKGROUND: We examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database. METHODS: Adult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups-VRE BSI, non-VRE BSI, without BSI-according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year. RESULTS: Of 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI], 2.2-3.7) and increased NRM (RR, 4.7; 99% CI, 3.6-6.2) (P < .0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, - mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P < .001 for all variables). CONCLUSIONS: VRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT.

Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with acute myeloid leukemia (AML). During transplantation, patients undergo a period of severe neutropenia, which puts them at high risk for infectious complications. However, the impact of patient colonization with multidrug-resistant organisms (MDRO) on overall survival remains unclear. METHODS: In this retrospective, single-center study, the authors analyzed data from 264 patients with AML who underwent a first allo-HSCT between January 2006 and March 2016 at their institution. Primary endpoints were overall survival and nonrelapse-related mortality. RESULTS: One hundred forty-two of 264 patients (53.8%) were colonized by at least 1 MDRO, mainly with vancomycin-resistant Enterococcus faecalis/faecium (n = 122). The characteristics of colonized patients did not differ from those of MDRO-negative patients with respect to median age (53.5 vs 53 years), cytogenetic risk according to European LeukemiaNet criteria, remission status before allo-HSCT (first or second complete remission: 55.7% vs 60.7%, respectively; active disease: 44.4% vs 39.3%, respectively), donor type, or hematopoietic cell transplantation-comorbidity index (HCT-CI). Compared with noncolonized patients, MDRO-positive patients had an inferior probability of survival at 5 years (43.3% vs 65.5%; P = .002), primarily because of a higher cumulative incidence of nonrelapse-related mortality (33.9% vs 9.4%; P < .001). Death caused by infections occurred in 15.5% of colonized patients versus 4.9% of noncolonized patients. There was no difference in the cumulative incidence of relapse in MDRO-positive versus MDRO-negative patients (33.8% vs 42.1%, respectively; P = .798). CONCLUSIONS: The current data emphasize the importance of regular MDRO screenings and prompt further investigations into the impact of colonization with MDRO on the immune system after allo-HSCT. Cancer 2018;124:286-96. © 2017 American Cancer Society.

A novel cysteine-free venom peptide with strong antimicrobial activity against antibiotics-resistant pathogens from the scorpion Opistophthalmus glabrifrons.

Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, pose serious threat to human health. The outbreak of antibiotic-resistant pathogens in recent years emphasizes once again the urgent need for the development of new antimicrobial agents. Here, we discovered a novel antimicrobial peptide from the scorpion Opistophthalmus glabrifrons, which was referred to as Opisin. Opisin consists of 19 amino acid residues without disulfide bridges. It is a cationic, amphipathic, and α-helical molecule. Protein sequence homology search revealed that Opisin shares 42.1-5.3% sequence identities to the 17/18-mer antimicrobial peptides from scorpions. Antimicrobial assay showed that Opisin is able to potently inhibit the growth of the tested Gram-positive bacteria with the minimal inhibitory concentration (MIC) values of 4.0-10.0 µM; in contrast, it possesses much lower activity against the tested Gram-negative bacteria and a fungus. It is interesting to see that Opisin is able to strongly inhibit the growth of methicillin- and vancomycin-resistant pathogens with the MICs ranging from 2.0 to 4.0 µM and from 4.0 to 6.0 µM, respectively. We found that at a concentration of 5 × MIC, Opisin completely killed all the cultured methicillin-resistant Staphylococcus aureus. These results suggest that Opisin is a promising therapeutic candidate for the treatment of the antibiotic-resistant bacterial infections.

Vancomycin-Resistant Enterococcus Endocarditis Complicated by Splenic Infarction and Embolic Stroke.

Infective endocarditis (IE) is a serious condition associated with high morbidity and mortality rates. The risk factors for IE include underlying heart disease, intravenous drug use, cardiac surgery, and interventional procedures. Enterococci are a common cause of IE, and vancomycin-resistant enterococci (VRE) infections are becoming increasingly prevalent. In this report, we present the case of an 88-year-old female patient with multiple cardiac comorbidities who developed VRE endocarditis with splenic infarction and embolic stroke. The patient was successfully treated with a combination of antibiotics and anticoagulation therapy. This report highlights the importance of recognizing the potential complications of VRE endocarditis and the need for appropriate management to prevent adverse outcomes. To the best of our knowledge, only one other case of VRE endocarditis with multiple systemic complications has been documented so far.

The Evaluation of Risk Factors for Vancomycin-Resistant Enterococcus Colonization and Infection Among Mixed Adult Intensive Care Unit Patients.

Background and objective Despite the adherence to strict infection control measures, vancomycin-resistant enterococcus (VRE) colonization and VRE infections are still important problems nowadays. However, there are only a limited number of studies examining the factors causing the transformation of VRE colonization to VRE infection in the intensive care unit (ICU). The aim of this study is to delineate the prevalence of VRE colonization and its transformation into infection and the risk factors leading to infection. Methods Patients admitted to the third-level mixed-type ICU from 2012 to 2015 for at least 24 hours and acquired VRE colonization and VRE infection, both during and after their admission, were included in the study, and their medical records were examined retrospectively. VRE rectal swabs were taken weekly from each patient on admission and discharge from the ICU. If the VRE-positive patient was detected negative for VRE on the rectal swap taken three times in total as a surveillance culture successively, this patient was accepted as VRE negative. Demographic data, Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores, invasive procedures, treatments (corticosteroid, antibiotic, etc.), nutrition types, laboratory results, and ICU results were recorded. Results Among 1730 patients admitted to ICU, 101 (5.8%) were found to carry VRE colonization. Twelve (11.8%) out of 101 patients colonized with VRE developed VRE infection. About 56.4% had urinary tract infections, 68.3% had pneumonia, 15.8% had surgical site infections, and 24.8% had catheter-associated infections among these infected patients. The most prevalent factor was Enterococcus faecium in patients with VRE colonization (64.3%) and infection (91%). VRE turned negative in 67% of patients with VRE colonization during their stay in ICU. Renal replacement therapy was statistically significant (p < 0.05) in the group with VRE infection (66.7%) compared to the VRE-colonized group (26.1%). Infection development risk among carriers of VRE for more than one week was again found statistically significant (p = 0.025). Demographic data, APACHE-II scores, treatments, nutrition type, previous antibiotic usage and types, invasive procedures, laboratory results, and ICU results were similar among the patients with VRE colonization and infection. Conclusion A longer duration of ICU stay in patients with colonization and previous renal replacement therapy increases the transformation of VRE colonization to VRE infection. Strategies toward decreasing VRE-colonized patients' period of stay in ICU is the main objective to control the rate of VRE infection.

Probiotics and Their Bioproducts: A Promising Approach for Targeting Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus.

Antibiotic resistance is a serious global health problem that poses a threat to the successful treatment of various bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Conventional treatment of MRSA and VRE infections is challenging and often requires alternative or combination therapies that may have limited efficacy, higher costs, and/or more adverse effects. Therefore, there is an urgent need to find new strategies to combat antibiotic-resistant bacteria. Probiotics and antimicrobial peptides (AMPs) are two promising approaches that have shown potential benefits in various diseases. Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. AMPs, usually produced with probiotic bacteria, are short amino acid sequences that have broad-spectrum activity against bacteria, fungi, viruses, and parasites. Both probiotics and AMPs can modulate the host immune system, inhibit the growth and adhesion of pathogens, disrupt biofilms, and enhance intestinal barrier function. In this paper, we review the current knowledge on the role of probiotics and AMPs in targeting multi-drug-resistant bacteria, with a focus on MRSA and VRE. In addition, we discuss future directions for the clinical use of probiotics.

The hidden microbiome of hospital infection surveillance testing: biomarkers of health outcomes in MRSA and VRE colonization.

Background: Hospital-acquired infections present a major concern for healthcare systems in the U.S. and worldwide. Drug-resistant infections result in increased costs and prolonged hospital stays. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for many drug-resistant infections in the U.S. We undertook two parallel studies aimed to investigate the differences in the microbial communities of individuals colonized with MRSA (or VRE) as compared to their respective non-colonized counterparts matched for age, sex, race, ethnicity, unit of admission, and diagnostic-related group, when available. Results: The VRE study showed considerably more Enterococcus genus communities in the VRE colonized samples. Our findings for both MRSA and VRE studies suggest a strong association between 16S rRNA gene alpha diversity, beta diversity, and colonization status. When we assessed the colonized microbial communities in isolation, the differences disappeared, suggesting that the colonized microbial communities drove the change. Isolating Staphylococcus, we saw significant differences expressed across colonization in specific sequence variants. Conclusions: The differences seen in the microbial communities from MRSA (or VRE) colonized samples as compared to non-colonized match-pairs are driven by the isolated communities of the Staphylococcus (or Enterococcus) genus, the removal of which results in the disappearance of any differences in the diversity observed across the match-pairs.

Catheter-Associated Vancomycin-Resistant Enterococcus faecium Ventriculitis and Multidrug-Resistant Acinetobacter baumannii Pneumonia With Subsequent Acinetobacter Ventriculitis: A Case Report.

Ventriculitis is associated with cerebrospinal fluid (CSF) shunts, and rare microorganisms associated with infection include vancomycin-resistant Enterococcus (VRE) faecium and Acinetobacter baumannii. Both organisms are known to cause nosocomial infections, and the emergence of multidrug-resistant (MDR) strains presents a treatment challenge. There is a lack of consensus on antimicrobial agent selection for ventriculitis involving VRE faecium or MDR A. baumannii, which are life-threatening conditions. We present a case of a 59-year-old male presenting with CSF catheter-associated VRE faecium ventriculitis and MDR A. baumannii pneumonia who subsequently developed a nosocomial MDR A. baumannii ventriculitis. Both instances of ventriculitis were successfully treated with combination antibiotic therapy. VRE faecium ventriculitis was successfully treated with linezolid and intrathecal daptomycin. While daptomycin is not approved for Enterococcal infections, the synergistic effect of daptomycin in combination with linezolid proved effective. Although the MDR A. baumannii pneumonia was not cured with cefiderocol monotherapy, the MDR A. baumannii ventriculitis was successfully treated with combination therapy including cefiderocol, ampicillin/sulbactam, and intrathecal colistin. This highlights life-saving combination antibiotic therapies for ventriculitis caused by multiple rare and drug-resistant microorganisms.

Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori, Japan.

BACKGROUND: Spread of vancomycin-resistant Enterococcus (VRE) is a global concern as a significant cause of healthcare-associated infections. A series of VRE faecium (VREf) outbreaks caused by clonal propagation due to interhospital transmission occurred in six general hospitals in Aomori prefecture, Japan. METHODS: The number of patients with VREf was obtained from thirty seven hospitals participating in the local network of Aomori prefecture. Thirteen hospitals performed active screening tests for VRE. Whole genome sequencing analysis was performed. RESULTS: The total number of cases with VREf amounted to 500 in fourteen hospitals in Aomori from Jan 2018 to April 2021. It took more than three years for the frequency of detection of VRE to return to pre-outbreak levels. The duration and size of outbreaks differed between hospitals according to the countermeasures available at each hospital. Whole genome sequencing analysis indicated vanA-type VREf ST1421 for most samples from six hospitals. CONCLUSIONS: This was the first multi-jurisdictional outbreak of VREf sequence type 1421 in Japan. In addition to strict infection control measures, continuous monitoring of VRE detection in local medical regions and smooth and immediate communication among hospitals are required to prevent VREf outbreaks.

Rapid and accurate eXDR screening: use Xpert Carba-R® with FecalSwab®.

The FecalSwab® displays high performances for stool culture, but it was not assessed for carbapenemase-producing Enterobacterales (CPE) screening. We assess the performances of the Xpert Carba-R v2® with the FecalSwab®. Using a collection of 12 CPE strains, the limit of detection was assessed at 158 CFU/swab [interquartile range 93-589]. In 2019, 1540 swabs were included by 4 hospital laboratories, of which 39 (2.5%) yield an invalid result. Among the 1501 valid, 87 (5.8%) were positives by culture and PCR and 25 (1.7%) were discrepant: 7 PCR-negative culture-positive, and 18 PCR-positive culture-negative. Two PCR-positive culture-negative results involved non-Enterobacterales strains: a KPC-producing Acinetobacter baumannii and a KPC-producing Aeromonas spp. The overall percent agreement was 98.3% and the Kappa value was 0.88. FecalSwab® is an accurate sampling device for CPE screening. It allows performing all eXDR screening using a single swab, simplifying the sample collection, and improving the patient comfort. Regarding discrepant, we suggest combining a CPE screening by both culture and Xpert Carba-R v2® methods.

Characterisation of ESKAPE Pathogens with Special Reference to Multidrug Resistance and Biofilm Production in a Nepalese Hospital.

BACKGROUND: "ESKAPE" is an acronym for a group of life-threatening nosocomial pathogens, viz, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. Global efforts on controlling multidrug-resistant (MDR) organisms have been hampered by their ability to escape antibacterial drugs. This study was undertaken to determine the prevalence of ESKAPE pathogens with prime focus on biofilm production and antibiotic resistance. METHODS: A total of 8756 clinical samples were processed for the isolation and identification of ESKAPE pathogens following standard microbiological procedures. These isolates were subjected to antimicrobial sensitivity test as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Test for MDR, extended-spectrum ß-lactamase (ESBL), metallo-ß-lactamase (MBL), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) was done by the disk diffusion and E-test methods. In the case of VRE molecular detection was done for vanA and vanB genes. All the isolates were processed for biofilm detection by the tube adherence method. RESULTS: The percentage distribution of Enterococcus faecium was 5.5%, S. aureus 33.4%, K. pneumoniae 33.0%, A. baumannii 8.6%, P. aeruginosa 18.6%, and Enterobacter aerogenes 0.9%. MRSA was 57.6%, and vancomycin resistance among Enterococcus faecium was 20%. ESBL- and MBL-producing K. pneumoniae were 16.1%, and 8.1%, A. baumannii 10.3% each and P. aeruginosa 10.7% and 8.3%, respectively. A total of 42.3% of isolates were biofilm producers. Linezolid was the drug of choice for VRE. Ampicillin-sulbactam was most useful against A. baumannii apart from polymyxins, whereas piperacillin-tazobactam was effective against other Gram-negative bacteria. VanA gene was detected in all the VRE isolates. CONCLUSION: This study estimates the burden of the ESKAPE organisms and their antimicrobial resistance pattern in a hospital setting. A high percentage of drug resistance and biofilm production was noted; hence antimicrobial resistance surveillance targeting ESKAPE pathogens should be incorporated in the infection control policy in Nepal.

A Rare Case of Enterococcus gallinarum-Associated Peritonitis and Literature Review.

Peritonitis is a well-known complication seen with peritoneal dialysis. Peritonitis is associated with increased mortality risk and is commonly caused by gram-positive and gram-negative bacteria, but it can also be the result of fungal or viral infections. Therefore, it is imperative to obtain a peritoneal fluid sample to send for cell count with differential, gram stain, and culture prior to starting empiric antibiotic therapy. We report a case of peritoneal dialysis-related peritonitis caused by Enterococcus gallinarum, for which there has only been one other reported case in the medical literature. Our patient was initially placed on vancomycin and cefepime but continued to deteriorate until peritoneal fluid cultures revealed E. gallinarum. Based on sensitivities, the patient was treated with daptomycin and cefazolin, which resolved her peritonitis.

Cajanin Stilbene Acid Inhibited Vancomycin-Resistant Enterococcus by Inhibiting Phosphotransferase System.

Antimicrobial resistance has become a serious threat to human and animal health, and vancomycin-resistant Enterococcus has become an important nosocomial infection pathogen, causing thousands of deaths each year. In this study, after screening a variety of natural products, we found that cajanin stilbene acid (CSA) had significant inhibitory effect on sensitive and vancomycin-resistant Enterococcus (VRE) in vitro. And we also confirmed that CSA had significant anti-VRE infection ability in vivo. Subsequently, we studied the antibacterial mechanism of CSA through proteomics experiments, and the results showed that CSA killed Enterococcus by inhibiting the phosphotransferase system of Enterococcus, thus hinders the normal growth and metabolic functions of bacteria. The results of this study provided evidence for the in-depth study on the mechanism of the antibacterial action of CSA and also provided a candidate for the development of anti-VRE drugs.

Prevalence and Resistance Profiles of Vancomycin-resistant Enterococcal Isolates in Iran; An Eight-month Report from Nine Major Cities.

BACKGROUND: Enterococcal infections comprise a wide range of diseases with increasing importance due to the growing frequency of health-care-associated infections and the increasing incidence of antimicrobial resistance. Vancomycin-resistant Enterococcus (VRE) is an emerging drug-resistant organism responsible for increasing numbers of nosocomial infections in both adults and children. Few data are available on the epidemiology and impact of VRE infections in Iranians. In the present study, attempts were made to evaluate the prevalence and molecular characterization of VRE isolates from patients referred to several hospitals in Iran. MATERIALS AND METHODS: Eight hundred and fourteen enterococcal clinical isolates from different patients were selected for this cross-sectional study during June 2018 and February 2019. Antimicrobial susceptibility testing was performed by standard methods according to the Clinical Laboratories Standards Institute (CLSI) guidelines. The vanA and vanB genes in VRE isolates were amplified by PCR. RESULTS: Our findings indicated that 20.7% of the isolates were collected from hospitalized patients in the ICU. Among all the isolates, 254 (30%) were identified as VRE strains. All of the VRE isolates were sensitive to linezolid. Moreover, only 39.9% of the VRE isolates harbored the vanA gene, while none of them carried the vanB gene. CONCLUSION: The present study reports the highest range of VRE infections in Iran. The constant surveillance and monitoring of VRE strains are recommended to limit the occurrence and spread of VRE clones within and among hospitals and community settings.

Asymptomatic carriage of extensively drug-resistant bacteria (eXDR), a simple way to assess spontaneous clearance.

The duration of eXDR carriage depends on several factors that might be difficult to recover. We aim to assess the duration of eXDR carriage by using a simple to recover parameter: the number of consecutive negative screening. 131 eXDR carriers (51 VRE and 80 CPE) were included. The number of consecutive negative screenings was strongly associated with eXDR clearance. All patients displaying at least three negative screenings over a seven-month period were never screened positive thereafter. Taking into account the number of negative screenings as a part of a case-by-case risk assessment would be helpful for the decision to maintain or lift eXDR-focused precautions.

Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008-2012).

The tendency of vancomycin, linezolid, and daptomycin MICs was investigated among 6920 staphylococci and enterococci during a 5-year period. Antimicrobial consumption was determined. Decrease of vancomycin MIC was detected associated with reduction in consumption. Linezolid and daptomycin remained active. An upward trend of linezolid MIC for methicillin-resistant staphylococci was observed.

Antibacterial effect of butyryl alkannin from Arnebia euchroma against vancomycin-resistant pathogens of Enterococcus faecalis causing urinary tract infections.

This study was carried out to investigate the biomedicinal potential of a bioactive marker component, butyryl alkannin, isolated from n-hexane root extract of Arnebia euchroma against various vancomycin-resistant Enterococcus (VRE) isolates of Enterococcus faecalis causing urinary tract infections. As a result, butyryl alkannin showed significant antibacterial activity against multidrug-resistant E. faecalis pathogens of VRE as minimum inhibitory concentration values which were found in the range of 3.13 to 6.26 µg ml(-1). The findings of this study justify biological and biomedicinal potential of butyryl alkannin compound as confirmed by its higher and significant antibacterial efficacy against VRE isolates of E. faecalis as compared to standard antibiotic vancomycin.

Antimicrobial activity of a UV-stable bacteriocin-like inhibitory substance (BLIS) produced by Enterococcus faecium strain DSH20 against vancomycin-resistant Enterococcus (VRE) strains.

BACKGROUND/PURPOSE: The narrow spectrum of action of most bacteriocins is an important limitation for their application as antimicrobial agents. The current study describes a novel bacteriocin-like inhibitory substance (BLIS) that display extended spectrum antimicrobial activity against vancomycin-resistant Enterococcus (VRE) strains. METHODS: Acquired resistance profiles of Enterococcus isolates determined based on the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) definition as multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug resistant (PDR). BLIS activity of Enterococcus isolates was investigated against Enterococcus faecalis (E. faecalis) ATCC 29212 as the indicator strain and clinical isolates including VRE, methicillin resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria containing Pseudomonas aeruginosa (P. aeruginosa), Klebsiella, Acinetobacter, and Escherichia coli (E. coli). RESULTS: Among 273 Enterococcus isolates, 27 and 2 VRE isolates, respectively, were XDR and PDR and eight isolates had BLIS activity against the indicator strain. One of these isolates, identified as E. faecium strain DSH20 based on its phenotypical and biochemical properties, as well as its 16S rRNA gene sequence, had potent BLIS production against all 29 VRE strains, but had no activity against MRSA, P. aeruginosa, Klebsiella, Acinetobacter, and E. coli strains. It was heat stable up to 121°C for 15 minutes (autoclave condition), active within the pH range of 3-9 and had UV stability, but its activity disappeared by treatment with proteinase K, pepsin, and trypsin, demonstrating its proteinaceous nature. It was designated as an approximately 35kDa peptide using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) method. CONCLUSION: This peptide is a potential agent for use as an alternative antibacterial agent for the treatment of drug-resistant strains of VRE infection.

Economic analysis of vancomycin-resistant enterococci at a Canadian hospital: assessing attributable cost and length of stay.

BACKGROUND: Competing resource demands have resulted in the de-escalation of vancomycin-resistant enterococcus (VRE) control programmes in some Canadian healthcare centres. AIM: To determine the attributable costs and length of stay (LOS) of VRE colonizations/infections in an acute care hospital in Canada. METHODS: Surveillance and financial hospital-based databases were used to conduct analyses with cases and controls from fiscal year 2008-2009 (1 April 2008 to 31 March 2009) at an acute care hospital in downtown Vancouver, Canada. A statistical analysis of attributable costs and LOS was conducted using a generalized linear model. In a secondary analysis, differences in costs and LOS were examined for VRE infections versus colonizations. FINDINGS: A total of 217 patients with VRE and a random sample of 1075 patients without VRE were examined. VRE has a positive and significant impact on patient hospitalization costs and LOS. Overall, the presence of VRE increased the estimated mean cost per patient by 61.9% (95% confidence interval: 42.3-84.3) in relative terms and $17,949 (13,949-21,464) in absolute Canadian dollars. For LOS, the attributable number of days associated with a VRE case mean was 68.0% (41.9-98.9) higher in relative terms and 13.8 days (10.0-16.9) in absolute days. In the secondary analysis comparing VRE infection and colonization costs, no statistically significant difference was found. CONCLUSIONS: Based on this analysis, the attributable cost and LOS of VRE are considerable. These factors should be considered before de-escalation of a hospital VRE control programme.