Lusutrombopag as a Repurposing Drug in Combination with Aminoglycosides against Vancomycin-Resistant Enterococcus.

Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

Promiscuous, persistent and problematic: insights into current enterococcal genomics to guide therapeutic strategy.

Vancomycin-resistant enterococci (VRE) are major opportunistic pathogens and the causative agents of serious diseases, such as urinary tract infections and endocarditis. VRE strains mainly include species of Enterococcus faecium and E. faecalis which can colonise the gastrointestinal tract (GIT) of patients and, following growth and persistence in the gut, can transfer to blood resulting in systemic dissemination in the body. Advancements in genomics have revealed that hospital-associated VRE strains are characterised by increased numbers of mobile genetic elements, higher numbers of antibiotic resistance genes and often lack active CRISPR-Cas systems. Additionally, comparative genomics have increased our understanding of dissemination routes among patients and healthcare workers. Since the efficiency of currently available antibiotics is rapidly declining, new measures to control infection and dissemination of these persistent pathogens are urgently needed. These approaches include combinatory administration of antibiotics, strengthening colonisation resistance of the gut microbiota to reduce VRE proliferation through commensals or probiotic bacteria, or switching to non-antibiotic bacterial killers, such as bacteriophages or bacteriocins. In this review, we discuss the current knowledge of the genomics of VRE isolates and state-of-the-art therapeutic advances against VRE infections.

Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice.

AIMS: Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections. METHODS AND RESULTS: The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection. CONCLUSIONS: The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model.

Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients.

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.

Comparative analysis of IR-Biotyper, MLST, cgMLST, and WGS for clustering of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit.

Healthcare-associated infections caused by vancomycin-resistant Enterococcus faecium (VREFM) pose a significant threat to healthcare. Confirming the relatedness of the bacterial isolates from different patients is challenging. We aimed to assess the efficacy of IR-Biotyper, multilocus sequencing typing (MLST), and core-genome MLST (cgMLST) in comparison with whole-genome sequencing (WGS) for outbreak confirmation in the neonatal intensive care unit (NICU). Twenty VREFM isolates from four neonates and ten control isolates from unrelated patients were analyzed. Genomic DNA extraction, MLST, cgMLST, and WGS were performed. An IR-Biotyper was used with colonies obtained after 24 h of incubation on tryptic soy agar supplemented with 5% sheep blood. The optimal clustering cutoff for the IR-Biotyper was determined by comparing the results with WGS. Clustering concordance was assessed using the adjusted Rand and Wallace indices. MLST and cgMLST identified sequence types (ST) and complex types (CT), revealing suspected outbreak isolates with a predominance of ST17 and CT6553, were confirmed by WGS. For the IR-Biotyper, the proposed optimal clustering cut-off range was 0.106-0.111. Despite lower within-run precision, of the IR-Biotyper, the clustering concordance with WGS was favorable, meeting the criteria for real-time screening. This study confirmed a nosocomial outbreak of VREFM in the NICU using an IR-Biotyper, showing promising results compared to MLST. Although within-run precision requires improvement, the IR-Biotyper demonstrated high discriminatory power and clustering concordance with WGS. These findings suggest its potential as a real-time screening tool for the detection of VREFM-related nosocomial outbreaks. IMPORTANCE: In this study, we evaluated the performance of the IR-Biotyper in detecting nosocomial outbreaks caused by vancomycin-resistant Enterococcus faecium, comparing it with MLST, cgMLST, and WGS. We proposed a cutoff that showed the highest concordance compared to WGS and assessed the within-run precision of the IR-Biotyper by evaluating the consistency in genetically identical strain when repeated in the same run.

Detection of linezolid and vancomycin resistant Enterococcus isolates collected from healthy chicken caecum.

AIM: The poultry industry represents an important economic sector in Tunisia. This study aims to determine the antimicrobial resistance phenotypes and genotypes and virulence factors of enterococci collected from chicken caecum in Tunisia. METHODS AND RESULTS: Forty-nine composite chicken caecum samples were recovered in 49 different Tunisian farms (December 2019-March 2020). Each composite sample corresponds to six individual caecum from each farm. Composite samples were plated on Slanetz-Bartley agar both supplemented (SB-Van) and not supplemented (SB) with vancomycin and isolates were identified by matrix-assisted laser desorption/ionization time-of-flight. Antibiotic resistance and virulence genes were tested by Polymerase Chain Reaction (PCR) and sequencing and multilocus-sequence-typing of selected enterococci was performed. One hundred sixty seven enterococci of six different species were recovered. Acquired linezolid resistance was detected in 6 enterococci of 4/49 samples (8.1%): (A) four optrA-carrying Enterococcus faecalis isolates assigned to ST792, ST478, and ST968 lineages; (B) two poxtA-carrying Enterococcus faecium assigned to ST2315 and new ST2330. Plasmid typing highlighted the presence of the rep10, rep14, rep7, rep8, and pLG1 in these strains. One vancomycin-resistant E. faecium isolate (typed as ST1091) with vanA gene (included in Tn1546) was detected in SB-Van plates. The gelE, agg, esp, and hyl virulence genes were found in linezolid- and vancomycin-resistant enterococci. High resistance rates were identified in the enterococci recovered in SB plates: tetracycline [74.8%, tet(M) and tet(L) genes], erythromycin [65.9%, erm(B)], and gentamicin [37.1%, aac(6')-Ie-aph(2″)-Ia]. CONCLUSION: The detection of emerging mechanisms of resistance related to linezolid and vancomycin in the fecal enterococci of poultry farms has public health implications, and further surveillance should be carried out to control their dissemination by the food chain.

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Enterococcus faecium is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical E. faecium isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant E. faecium (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent E. faecium bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related E. faecium strains for at least 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient's gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient's antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and E. faecium. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections. IMPORTANCE: Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Protective effect of microbisporicin (NAI-107) against vancomycin resistant Enterococcus faecium infection in a Galleria mellonella model.

Increasing antimicrobial resistance in Enterococcus faecium necessitates the search for novel treatment agents, such as bacteriocins. In this study, we conducted an in vivo assessment of five bacteriocins, namely Lacticin Z, Lacticin Q, Garvicin KS (ABC), Aureocin A53 and Microbisporicin (NAI-107), against vanB-resistant Enterococcus faecium using a Galleria mellonella model. Our in vitro experiments demonstrated the efficacy of all five bacteriocins against vanB-resistant E. faecium with only NAI-107 demonstrating in vivo efficacy. Notably, NAI-107 exhibited efficacy across a range of tested doses, with the highest efficacy observed at a concentration of 16 µg/mL. Mortality rates in the group treated with 16 µg/mL NAI-107 were lower than those observed in the linezolid-treated group. These findings strongly suggest that NAI-107 holds promise as a potential alternative therapeutic agent for treating infections caused by resistant E. faecium and warrants further investigation.

Adaptation and validation of a quantitative vanA/vanB DNA screening assay on a high-throughput PCR system.

Vancomycin resistant enterococci (VRE) are a leading cause of ICU-acquired bloodstream infections in Europe. The bacterial load in enteral colonization may be associated with a higher probability of transmission. Here, we aimed to establish a quantitative vanA/vanB DNA real-time PCR assay on a high-throughput system. Limits of detection (LOD), linear range and precision were determined using serial bacterial dilutions. LOD was 46.9 digital copies (dcp)/ml for vanA and 60.8 dcp/ml for vanB. The assay showed excellent linearity between 4.7 × 101 and 3.5 × 105 dcp/ml (vanA) and 6.7 × 102 and 6.7 × 105 dcp/ml (vanB). Sensitivity was 100% for vanA and vanB, with high positive predictive value (PPV) for vanA (100%), but lower PPV for vanB (34.6%) likely due to the presence of vanB DNA positive anerobic bacteria in rectal swabs. Using the assay on enriched VRE broth vanB PPV increased to 87.2%. Quantification revealed median 2.0 × 104 dcp/ml in PCR positive but VRE culture negative samples and median 9.1 × 104 dcp/ml in VRE culture positive patients (maximum: 107 dcp/ml). The automated vanA/B_UTC assay can be used for vanA/vanB detection and quantification in different diagnostic settings and may support future clinical studies assessing the impact of bacterial load on risk of infection and transmission.

Introduction and spread of vancomycin-resistant Enterococcus faecium (VREfm) at a German tertiary care medical center from 2004 until 2010: a retrospective whole-genome sequencing (WGS) study of the molecular epidemiology of VREfm.

BACKGROUND: In most of Europe and especially in Germany, there is currently a concerning rise in the number of hospital-acquired infections due to vancomycin-resistant Enterococcus faecium (VREfm). Therefore, there is a need to improve our understanding of the way VREfm spreads in hospitals. In this study, we investigated the molecular epidemiology of VREfm isolates from the first appearance at our university hospital in 2004 until 2010. There is only very scarce information about the molecular epidemiology of VREfm from this early time in Germany. METHODS: Our analysis includes all available first VREfm isolates of each patient at our tertiary care center collected during the years 2004-2010. If available, additional consecutive VREfm isolates from some patients were analyzed. We used multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) for the analysis and description of nosocomial transmission pathways as well as the detection of outbreaks. RESULTS: VREfm isolates from 158 patients and 76 additional subsequent patient isolates were included in the analysis. Until 2006, detections of VREfm remained singular cases, followed by a peak in the number of VREfm cases in 2007 and 2008 with a subsequent decline to baseline in 2010. MLST and cgMLST analysis show significant changes in the dominant sequence types (STs) and complex types (CTs) over the study period, with ST192 and ST17 being responsible for the peak in VREfm cases in 2007 and 2008. The four largest clusters detected during the study period are comprised of these two STs. Cluster analysis shows a focus on specific wards and departments for each cluster. In the early years of this study (2004-2006), all analyzed VREfm stemmed from clinical specimens, whereas since 2007, approximately half of the VREfm were detected by screening. Of the 234 VREfm isolates analyzed, 96% had a vanB and only 4% had a vanA resistance genotype. CONCLUSIONS: This retrospective study contributes significant knowledge about regional VREfm epidemiology from this early VREfm period in Germany. One remarkable finding is the striking dominance of vanB-positive VREfm isolates over the entire study period, which is in contrast with countrywide data. Analysis of cgMLST shows the transition from sporadic VRE cases at our institution to a sharp increase in VRE numbers triggered by oligoclonal spread and specific outbreak clusters with the dominance of ST192 and ST17.

Epidemiology and infection control of vancomycin-resistant enterococci at a German university hospital: A three-year retrospective cohort study.

Vancomycin-resistant enterococci (VRE) occur in hospitalized patients, causing both infection and colonization. In recent years, there has been an increase in VRE in German and other hospitals, raising the question of how to control this epidemic best. To better understand the specific epidemiology and to guide infection control, we conducted a retrospective cohort study analyzing all patients with VRE at Hannover Medical School, a tertiary university clinic in Germany that specializes in solid organ transplantation. Epidemiologic and clinical characteristics of patients with VRE from 2015-2017 were collected. Basic epidemiologic parameters, including VRE incidence and incidence density, were calculated. Independent risk factors for nosocomial VRE infection compared to colonization were assessed using a logistic regression model. There were 1,492 VRE cases corresponding to 822 individual patients. The incidence was 0.8 VRE cases per 100 cases. A total of 536 (35.9%) of the 1,492 VRE cases were acquired nosocomially. Of the 1,492 cases, 912 cases had VRE-positive samples (894 Enterococcus (E.) faecium and 18 E. faecalis) in our hospital laboratory and the remaining cases were known VRE carriers. The vanB-phenotype was observed in 369 of the 894 (41.3%) E. faecium isolates and in 6 of the 18 (33.3%) E. faecalis isolates. There was an increase over time in the vanB-phenotype proportion in E. faecium (2015: 63 of 171, 36.8%, 2016: 115 of 322, 35.7% and 2017: 191 of 401, 47.6%). A total of 107 cases had a VRE infection (7.2% of all VRE cases) according to the criteria of the German National Reference Center for Surveillance of Nosocomial Infections. The remaining cases were only colonized. Among other factors, leukocytopenia (<1,000/µL), the use of a central venous catheter and the visceral surgery medical specialty were independently associated with nosocomial VRE infection. VRE imposed a relevant and increasing infection control burden at our hospital. Nosocomial VRE infection was predominantly found in certain medical specialties, such as hematology and oncology and visceral surgery. Infection control efforts should focus on these highly affected patient groups/specialties.

The pathogenicity of vancomycin-resistant Enterococcus faecalis to colon cancer cells.

BACKGROUND: The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro. METHODS: Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured by Western blotting. RESULTS: The growth and adhesion of E. faecalis at a multiplicity of infection (MOI) of 1:1 were greater than those at a MOI of 100:1(p < 0.05). Compared to E. faecalis ATCC 29212, VREs showed less invasive effect on NCM460 and HT-29 cells. E. faecalis promoted angiogenesis by secreting IL-8 and VEGFA in colon cells, and the cells infected with VREs produced more than those infected with the standard strain (p < 0.05). Additionally, the PI3K/AKT/mTOR signaling pathway was activated in E. faecalis infected cells, with VREs demonstrating a greater activation compared to E. faecalis ATCC 29212 (p < 0.05). CONCLUSION: VREs contribute to the occurrence and development of CRC by promoting angiogenesis and activating the PI3K/AKT/mTOR signaling pathway.

Vancomycin-resistant Enterococcus faecium: impact of ending screening and isolation in a Danish University hospital.

BACKGROUND: Substantial resources are used in hospitals worldwide to counteract the ever-increasing incidence of vancomycin-resistant and vancomycin-variable Enterococcus faecium (VREfm and VVEfm), but it is important to balance patient safety, infection prevention, and hospital costs. AIM: To investigate the impact of ending VREfm/VVEfm screening and isolation at Odense University Hospital (OUH), Denmark, on patient and clinical characteristics, risk of bacteraemia, and mortality of VREfm/VVEfm disease at OUH. The burden of VREfm/VVEfm bacteraemia at OUH and the three collaborative hospitals in the Region of Southern Denmark (RSD) was also investigated. METHODS: A retrospective cohort study was conducted including first-time VREfm/VVEfm clinical isolates (index isolates) detected at OUH and collaborative hospitals in the period 2015-2022. The intervention period with screening and isolation was from 2015 to 2021, and the post-intervention period was 2022. Information about clinical isolates was retrieved from microbiological databases. Patient data were obtained from hospital records. FINDINGS: At OUH, 436 patients were included in the study, with 285 in the intervention period and 151 in the post-intervention period. Ending screening and isolation was followed by an increased number of index isolates. Besides a change in van genes, only minor non-significant changes were detected in all the other investigated parameters. Mortality within 30 days did not reflect the VREfm/VVEfm-attributable deaths, and in only four cases was VREfm/VVEfm infection the likely cause of death. CONCLUSION: Despite an increasing number of index isolates, nothing in the short follow-up period supported a reintroduction of screening and isolation.

Role of membrane vesicles in the transmission of vancomycin resistance in Enterococcus faecium.

Clonal transmission and horizontal gene transfer (HGT) contribute to the spread of vancomycin-resistant enterococci (VRE) in global healthcare. Our study investigated vesiduction, a HGT mechanism via membrane vesicles (MVs), for vanA and vanB genes that determine vancomycin resistance. We isolated MVs for VRE of different sequence types (STs) and analysed them by nanoparticle tracking analysis. Selected MV samples were subjected to DNA sequence analysis. In resistance transfer experiments, vancomycin-susceptible enterococci were exposed to MVs and bacterial supernatants of VRE. Compared to bacteria grown in lysogeny broth (MVs/LB), cultivation under vancomycin stress (MVs/VAN) resulted in increased particle concentrations of up to 139-fold (ST80). As a key finding, we could show that VRE isolates of ST80 and ST117 produced remarkably more vesicles at subinhibitory antibiotic concentrations (approx. 9.2 × 1011 particles/ml for ST80 and 2.4 × 1011 particles/ml for ST117) than enterococci of other STs (range between 1.8 × 1010 and 5.3 × 1010 particles/ml). In those MV samples, the respective resistance genes vanA and vanB were completely verifiable using sequence analysis. Nevertheless, no vancomycin resistance transfer via MVs to vancomycin-susceptible Enterococcus faecium was phenotypically detectable. However, our results outline the potential of future research on ST-specific MV properties, promising new insights into VRE mechanisms.

A Review of the Evidence on the Role of Floors and Shoes in the Dissemination of Pathogens in a Healthcare Setting.

Background: It is generally accepted that shoes and floors are contaminated with pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile, yet correlation to clinical infection is not well established. Because floors and shoes are low-touch surfaces, these are considered non-critical surfaces for cleaning and disinfection. The purpose of this review is to assess peer-reviewed literature inclusive of floors and shoe soles as contributors to the dissemination of infectious pathogens within healthcare settings. Methods: Using the Preferred Reporting Items for Systematic Reviews (PRISMA) methodology, PubMed and Medline were searched for articles assessing the presence of pathogens on or the transmission of pathogens between or from floors or shoe soles/shoe covers. Inclusion criteria are the human population within healthcare or controlled experimental settings after 1999 and available in English. Results: Four hundred eighteen articles were screened, and 18 articles documented recovery of bacterial and viral pathogens from both floors and shoes. Seventy-two percent (13/18) of these were published after 2015, showing increased consideration of the transfer of pathogens to high-touch surfaces from shoe soles or floors during patient care. Conclusions: There is evidence that floors and shoes in healthcare settings are contaminated with several different species of health-care-associated pathogens including MRSA, VRE, and Clostridium difficile.

Uropathogenic distribution and antibiotic resistance patterns according to multidrug-resistant bacteria colonization status in patients with stroke.

Urinary tract infections (UTI) are common in patients with stroke. The colonization of multidrug-resistant organisms (MDR) has recently become a global issue, and infection with MDR is associated with a poorer prognosis. This study aimed to investigate the uropathogenic distribution in stroke patients according to MDR colonization and investigate the infection risk and antibiotic resistance of each uropathogen to help determine initial antibiotic treatment. This study is a retrospective study conducted on patients who underwent inpatient treatment for stroke at Kosin University Gospel Hospital in 2019 to 2021. The participants were classified into Group VRE if vancomycin-resistant Enterococcus (VRE) colonization was confirmed, Group CRE if carbapenem-resistant Enterobacteriaceae (CRE) colonization was confirmed, and Group Negative if no MDR colonization was confirmed. Urine culture was performed if symptomatic UTI was suspected. Uropathogenic distribution, antibiotic resistance patterns were assessed by one-way analysis of variance, independent t-test, and Pearson chi-square test. And the infection risk factors for each uropathogen were assessed by multinomial logistic regression analysis. Six hundred thirty-three participants were enrolled. The mean age of all participants was 69.77 ±â€…14.91, with 305 males and 328 females, including 344 hemorrhagic strokes and 289 ischemic strokes. No growth in urine culture was the most common finding (n = 281), followed by Escherichia coli (E.coli) (n = 141), and Enterococcus spp. (n = 80). Group Negative had significantly more cases of no growth in urine culture than Group VRE (Odds ratio [OR], 11.698; 95% confidence interval [CI], 3.566-38.375; P < .001) and than Group CRE (OR, 11.381; 95% CI, 2.665-48.611; P < .001). Group VRE had significantly more E.coli (OR, 2.905; 95% CI, 1.505-5.618; P = .001), and more Enterococcus (OR, 4.550; 95% CI, 2.253-9.187; P < .001) than Group Negative. There was no statistical difference in antibiotic resistance according to MDR colonization in E coli, but for Enterococcus spp., Group VRE and CRE showed significantly more resistance to numerous antibiotics than Group Negative. MDR colonization increases the risk of UTI and is associated with greater antibiotic resistance. For appropriate administration of antibiotics in UTI, continuous monitoring of the latest trends in uropathogenic distribution is required, and clinicians should pay more attention to the use of initial empirical antibiotics in patients with MDR colonization.

Activity of a foam in preventing rebound of vancomycin-resistant Enterococcus faecium-containing droplets generated from the toilet bowl.

In hospital environments, droplets generated by urination within shared toilets may represent a route of dissemination for bacteria such as vancomycin-resistant Enterococcus faecium (VREfm), which contributes significantly to the burden of hospital-acquired infections. We investigated the potential activity of a foam in preventing the generation of droplets containing Enterococcus spp. during urination. A uniform layer of foam was deposited in the inner walls and at the bottom of an experimental toilet contaminated with suspensions of Enterococcus strains (including a VREfm strain). Human urination was simulated, and colonies of Enterococcus were recovered through a toilet lid where agar plates had been placed. Results showed that the foam was able to suppress production of droplets containing Enterococcus spp. generated by a liquid hitting inner toilet walls. Conversely, Enterococcus colonies were recovered in absence of foam. Moreover, the foam did not show antibacterial activity. We propose a new non-antimicrobial approach aimed at limiting transmission of multidrug-resistant bacteria, particularly in healthcare settings.

Perioperative daptomycin for prophylaxis of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients.

BACKGROUND: Infection with vancomycin-resistant Enterococcus (VRE) in liver transplant recipients (LTR) has been associated with extended hospital stays, increased readmission rates, graft failure, and death. A tailored perioperative surgical prophylaxis regimen targeting VRE may reduce postoperative infections in VRE-colonized patients. This study investigated the outcomes of perioperative daptomycin in this patient population. METHODS: This retrospective, single-center cohort study included LTR ≥ 18 years old who were VRE-colonized from June 2018 to November 2022. VRE colonization was identified by a VRE rectal swab screen or a positive VRE culture prior to transplant. Two groups were analyzed: daptomycin versus no daptomycin. All LTR received perioperative piperacillin-tazobactam for 24 h. If VRE-colonized, one dose of daptomycin (6 mg/kg) was given pre- and postoperatively. Demographics, clinical characteristics, risk factors for VRE infection, and daptomycin dose were collected. The primary outcome was VRE infection at 14 days and 90 days post-transplant. RESULTS: There were 36 VRE-colonized LTR; 19 received daptomycin and 17 did not. Baseline characteristics and risk factors for VRE infection were similar between groups. More VRE infections occurred in the no daptomycin group within 14 days post-transplant (24% vs. 0%, p = .04), but at 90 days posttransplant there was no significant difference (29% vs. 16%, p = .43). The average daptomycin dose was 7.1 mg/kg. CONCLUSION: Perioperative daptomycin reduced the rate of VRE infections in VRE-colonized LTR within 14 days posttransplant but not at 90 days. Future studies should evaluate if higher doses and/or longer duration of perioperative daptomycin can reduce VRE infections beyond 14 days post-transplant.