RESUMO
Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
Assuntos
Citocinas , Modelos Animais de Doenças , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Interações Hospedeiro-Patógeno , Peritonite , Sepse , Enterococos Resistentes à Vancomicina , Animais , Peritonite/microbiologia , Peritonite/imunologia , Camundongos , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Enterococos Resistentes à Vancomicina/patogenicidade , Sepse/microbiologia , Sepse/imunologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/imunologia , Macrófagos/microbiologia , Transdução de SinaisRESUMO
Healthcare associated infections (HAIs) are costly but preventable. A limited understanding of the effects of environmental cleaning on the riskiest HAI associated pathogens is a current challenge in HAI prevention. This project aimed to quantify the effects of terminal hospital cleaning practices on HAI pathogens via environmental sampling in three hospitals located throughout the United States. Surfaces were swabbed from 36 occupied patient rooms with a laboratory-confirmed, hospital- or community-acquired infection of at least one of the four pathogens of interest (i.e., Acinetobacter baumannii (A. baumannii), methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus faecalis/faecium (VRE), and Clostridioides difficile (C. difficile)). Six nonporous, high touch surfaces (i.e., chair handrail, bed handrail, nurse call button, desk surface, bathroom counter near the sink, and a grab bar near the toilet) were sampled in each room for Adenosine Triphosphate (ATP) and the four pathogens of interest before and after terminal cleaning. The four pathogens of interest were detected on surfaces before and after terminal cleaning, but their levels were generally reduced. Overall, C. difficile was confirmed on the desk (n = 2), while MRSA (n = 24) and VRE (n = 25) were confirmed on all surface types before terminal cleaning. After cleaning, only MRSA (n = 6) on bed handrail, chair handrail, and nurse call button and VRE (n = 5) on bathroom sink, bed handrail, nurse call button, toilet grab bar, and C. difficile (n = 1) were confirmed. At 2 of the 3 hospitals, pathogens were generally reduced by >99% during terminal cleaning. One hospital showed that VRE increased after terminal cleaning, MRSA was reduced by 73% on the nurse call button, and VRE was reduced by only 50% on the bathroom sink. ATP detections did not correlate with any pathogen concentration. This study highlights the importance of terminal cleaning and indicates room for improvement in cleaning practices to reduce surface contamination throughout hospital rooms.
Assuntos
Clostridioides difficile , Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Quartos de Pacientes , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Clostridioides difficile/isolamento & purificação , Zeladoria Hospitalar , Acinetobacter baumannii/isolamento & purificação , Controle de Infecções/métodos , Enterococos Resistentes à Vancomicina/isolamento & purificaçãoRESUMO
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.
Assuntos
Infecções Bacterianas , Bacteriocinas , Enterococcus faecium , Enterococos Resistentes à Vancomicina , Animais , Camundongos , Bacteriocinas/farmacologia , Hemólise , Estudos de Viabilidade , Antibacterianos/farmacologia , Peptídeos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
The rise of Vancomycin-resistant enterococci (VRE) strains among cellular therapy recipients raises concerns due to increased morbidity, mortality, and hospitalization costs, particularly impacting transplanted patients with diminished survival expectations. Recent research linking lactose to Enterococcus growth and graft-versus-host disease (GVHD) emphasizes the need for data on reducing lactose in the diets of VRE-carrying patients, especially in cellular therapy contexts like CAR-T or allogeneic hematopoietic stem cell transplantation. Responding to elevated VRE positivity rates in rectal swabs among patients in our BMT Unit, a unique nutritional strategy was implemented, introducing lactose-free milk and strictly enforcing lactose-free diets. This approach resulted in a significant reduction in VRE carriers, with a 16% positivity rate in the Lactose Group versus 3.6% in the Lactose-Free Group, as of June 2023. These results indicate the potential efficacy of this innovative nutritional strategy in high-risk departments, such as BMT Units and Intensive Care Units, with implications for reducing isolation strategies and inappropriate antibiotic use in cases of VRE colonization.
Assuntos
Enterococos Resistentes à Vancomicina , Humanos , Lactose , Infecções por Bactérias Gram-Positivas/prevenção & controle , Masculino , Feminino , Leite/microbiologia , Transplante de Medula ÓsseaRESUMO
BACKGROUND: The duration of extensively drug-resistant bacteria (XDR) carriage depends on several factors for which the information can be difficult to recover. AIM: To determine whether past screening and clinical results of patients can predict the results of subsequent screening. METHODS: In total, 256 patients were retrospectively included from 10 healthcare centres in France from January 2014 to January 2022. We created a predictive clearance score, ranging from -5 to +7, that included the number of XDR species and the type of resistance detected in the sample, as well as the time from the last positive sample, the number of previous consecutive negative samples, and obtaining at least one negative PCR result in the collection. This score could be used for the upcoming rectal screening of a patient carrying an XDR as soon as the last screening sample was negative. FINDINGS: The negative predictive value was >99% for score ≤0. The median time to achieve XDR clearance was significantly shorter for a score of 0 (443 days (259-705)) than that based on previously published criteria. CONCLUSION: This predictive score shows high performance for the assessment of XDR clearance. Relative to previous guidelines, it could help to lift specific infection prevention and control measures earlier. Nevertheless, the decision should be made according to other factors, such as antimicrobial use and adherence to hand hygiene.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Programas de Rastreamento , Enterococos Resistentes à Vancomicina , Humanos , Estudos Retrospectivos , França/epidemiologia , Programas de Rastreamento/métodos , Enterococos Resistentes à Vancomicina/isolamento & purificação , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Portador Sadio/microbiologia , Masculino , Feminino , Infecções por Enterobacteriaceae/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Pessoa de Meia-Idade , Idoso , Valor Preditivo dos Testes , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
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.
Assuntos
Neoplasias do Colo , Enterococos Resistentes à Vancomicina , Humanos , Enterococcus faecalis , Vancomicina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Interleucina-8 , Fosfatidilinositol 3-Quinases/metabolismo , Virulência , Serina-Treonina Quinases TOR/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismoRESUMO
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.
Assuntos
Infecção Hospitalar , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Humanos , Enterococos Resistentes à Vancomicina/genética , Hospitais Universitários , Estudos Retrospectivos , Controle de Infecções , Infecção Hospitalar/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , AntibacterianosRESUMO
OBJECTIVES: We aimed to investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in paediatric patients from Hospital Pequeno Príncipe. The susceptibility profile was determined, and whole-genome sequencing (WGS) was used to analyse the genetic context of the strains. METHODS: Five VREfm isolates were recovered from sterile sites and surveillance cultures of two paediatric patients with acute lymphoblastic leukaemia. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and the minimum inhibitory concentration (MIC) was assessed according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST). WGS was performed to analyse the genetic context of virulence and resistance genes, and in silico multilocus sequence typing was performed to identify the sequence typing of the strains. RESULTS: High-level vancomycin resistance was observed in all isolates (≥256 mg/L). WGS revealed the presence of mobile genetic elements, such as plasmids (rep2, rep11a, repUS15, rep17, and rep18a), insertion sequences, and phages. Multiple resistance genes (aac(6')-aph(2"), dfrG, ermB, and vanA) and virulence genes (acm and efaAfm) were identified. All the isolates were assigned to ST117 (ST1133 - via a novel MLST), an important epidemic lineage associated with nosocomial infections and outbreaks. CONCLUSION: Our results show that the ST117 (ST1133) VREfm isolates are circulating in paediatric patients, which raises a great concern. The development of new drugs as well as the implementation of an antimicrobial stewardship program are necessary for their correct management, limiting the spread of resistance in oncohematological patients.
Assuntos
Enterococcus faecium , Leucemia-Linfoma Linfoblástico de Células Precursoras , Enterococos Resistentes à Vancomicina , Humanos , Criança , Vancomicina/farmacologia , Tipagem de Sequências Multilocus , Brasil/epidemiologia , Genótipo , Enterococos Resistentes à Vancomicina/genética , Surtos de DoençasRESUMO
Surveillance has revealed an increase of multidrug-resistant organisms (MDROs), even in low-prevalent settings such as Norway. MDROs pose a particular threat to at-risk populations, including persons with cancer. It is necessary to include such populations in future infection surveillance. By combining existing data sources, we aimed to describe the epidemiology of MDROs in persons diagnosed with cancer in Norway from 2008 to 2018. A cohort was established using data from the Cancer Registry of Norway, which was then linked to notifications of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- and/or linezolid-resistant enterococci (V/LRE), and carbapenemase-producing Gram-negative bacilli (CP-GNB) from the Norwegian Surveillance System for Communicable Diseases, and laboratory data on third-generation cephalosporin-resistant Enterobacterales (3GCR-E) from Oslo University Hospital (OUH). We described the incidence of MDROs and resistance proportion in Enterobacterales from 6 months prior to the person's first cancer diagnosis and up to 3 years after. The cohort included 322,005 persons, of which 0.3% (878) were diagnosed with notifiable MDROs. Peak incidence rates per 100,000 person-years were 60.9 for MRSA, 97.2 for V/LRE, and 6.8 for CP-GNB. The proportion of 3GCR-E in Enterobacterales in blood or urine cultures at OUH was 6% (746/12,534). Despite overall low MDRO incidence, there was an unfavourable trend in the incidence and resistance proportion of Gram-negative bacteria. To address this, there is a need for effective infection control and surveillance. Our study demonstrated the feasibility of expanding the surveillance of MDROs and at-risk populations through the linkage of existing laboratory and register data.
Assuntos
Doenças Transmissíveis , Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Neoplasias , Enterococos Resistentes à Vancomicina , Humanos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Neoplasias/epidemiologiaRESUMO
BACKGROUND: This study was designed to determine changes in risk factors on the prognosis of patients during each period of the bloodstream infection (BSI) timeline. METHODS: Through an integrated study of multivariable regressions with machine learning techniques, the risk factors for mortality during each period of BSI were analyzed. RESULTS: A total of 302,303 inpatients who underwent blood cultures during 2011-2021 were enrolled. More than 8 % of BSI cases progressed to subsequent BSI, and risk factors were identified as gut colonization with vancomycin-resistant enterococci (aOR 1.82; 95 % CI 1.47-2.24), intensive care unit admission (aOR 3.37; 95 % CI 3.35-4.28), and current cancer chemotherapy (aOR 1.54; 95 % CI 1.36-1.74). The mean SOFA score of the deceased patients during the first 7 days was 10.6 (SD 4.3), which was significantly higher than those on days 8-30 (7.0 ± 4.2) and after Day 30 (4.0 ± 3.5). BSIs caused by Acinetobacter baumannii and Candida albicans were more likely to result in deaths of patients for all time periods (all, P < 0.001). BSIs caused by Enterococcus faecalis and Enterococcus faecium were associated with a poor outcome in the period after Day 30 (both, P < 0.001). Nonsusceptible phenotypes to ß-lactam/ß-lactamase inhibitors of Escherichia coli and Klebsiella pneumoniae influenced the prognoses of patients with BSI in terms of high mortality rates during both days 8-30 and after Day 30. CONCLUSION: Influence of microbiological factors on mortality, including BSI-causative microorganisms and their major antimicrobial resistance, was emphasized in both periods of days 8-30 and after Day 30.
Assuntos
Bacteriemia , Sepse , Enterococos Resistentes à Vancomicina , Humanos , Bacteriemia/microbiologia , Estudos Retrospectivos , Sepse/complicações , Fatores de Risco , Escherichia coliRESUMO
BACKGROUND: Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group. METHODS: A retrospective, single center, case-control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (≥ 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization. RESULTS: A total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively). CONCLUSIONS: Antimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.
Assuntos
Infecção Hospitalar , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Humanos , Vancomicina/uso terapêutico , Estudos de Casos e Controles , Estudos Retrospectivos , Infecções por Bactérias Gram-Positivas/epidemiologia , Resistência a Vancomicina , Fatores de Risco , HospitaisRESUMO
PURPOSE: Superficial surgical site infections (SSI) are a common complication after abdominal surgery. Additionally, multidrug-resistant organisms (MDRO) have shown an increasing spread in recent years with a growing importance for health care. As there is varying evidence on the importance of MDRO in different surgical fields and countries as causative agents of SSI, we report our findings of MDRO-caused SSI. METHODS: We assembled an institutional wound register spanning the years 2015-2018 including all patients with abdominal surgery and SSI only, including demographics, procedure-related data, microbiological data from screenings, and body fluid samples. The cohort was examined for the frequency of different MDRO in screenings, body fluids, and wound swabs and assessed for risk factors for MDRO-positive SSI. RESULTS: A total of 138 out of 494 patients in the register were positive for MDRO, and of those, 61 had an MDRO isolated from their wound, mainly multidrug-resistant Enterobacterales (58.1%) followed by vancomycin-resistant Enterococcus spp. (19.7%). As 73.2% of all MDRO-carrying patients had positive rectal swabs, rectal colonization could be identified as the main risk factor for an SSI caused by a MDRO with an odds ratio (OR) of 4.407 (95% CI 1.782-10.896, p = 0.001). Secondly, a postoperative ICU stay was also associated with an MDRO-positive SSI (OR 3.73; 95% CI 1.397-9.982; p = 0.009). CONCLUSION: The rectal colonization status with MDRO should be taken into account in abdominal surgery regarding SSI prevention strategies. Trial registration Retrospectively registered in the German register for clinical trials (DRKS) 19th December 2019, registration number DRKS00019058.
Assuntos
Infecção da Ferida Cirúrgica , Enterococos Resistentes à Vancomicina , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Farmacorresistência Bacteriana Múltipla , Reto/cirurgia , Fatores de Risco , AntibacterianosRESUMO
BACKGROUND: Patients with cancer are at risk of multidrug-resistant bacteria colonization, but association of colonization with in-hospital mortality and one-year survival has not been established in critically ill patients with cancer. METHODS: Using logistic and Cox-regression analyses adjusted for confounders, in adult patients admitted at intensive care unit (ICU) with active cancer, we evaluate the association of colonization by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci with in-hospital mortality and one-year survival. RESULTS: We included 714 patients and among them 140 were colonized (19.6%). Colonized patients more frequently came from ward, had longer hospital length of stay before ICU admission, had unplanned ICU admission, had worse performance status, higher predicted mortality upon ICU admission, and more hematological malignancies than patients without colonization. None of the patients presented conversion of colonization to infection by the same bacteria during hospital stay, but 20.7% presented conversion to infection after hospital discharge. Colonized patients had a higher in-hospital mortality compared to patients without colonization (44.3 vs. 33.4%; p < 0.01), but adjusting for confounders, colonization was not associated with in-hospital mortality [Odds ratio = 1.03 (0.77-1.99)]. Additionally, adjusting for confounders, colonization was not associated with one-year survival [Hazard ratio = 1.10 (0.87-1.40)]. CONCLUSIONS: Adult critically ill patients with active cancer and colonized by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci active cancer have a worse health status compared to patients without colonization. However, adjusting for confounders, colonization by carbapenem-resistant Gram-negative bacteria or vancomycin-resistant enterococci are not associated with in-hospital mortality and one-year survival.
Assuntos
Infecções por Bactérias Gram-Positivas , Neoplasias Hematológicas , Enterococos Resistentes à Vancomicina , Adulto , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Estado Terminal , Mortalidade Hospitalar , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Bactérias Gram-NegativasRESUMO
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.
Assuntos
Enterococos Resistentes à Vancomicina , Enterococos Resistentes à Vancomicina/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Transcrição/metabolismo , Histidina Quinase/genética , Histidina Quinase/metabolismo , Nucleotídeos , Trifosfato de Adenosina , Antibacterianos/metabolismoRESUMO
Antibiotic resistance critically limits treatment options for infection caused by opportunistic pathogens such as enterococci. Here, we investigate the antibiotic and immunological activity of the anticancer agent mitoxantrone (MTX) in vitro and in vivo against vancomycin-resistant Enterococcus faecalis (VRE). We show that, in vitro, MTX is a potent antibiotic against Gram-positive bacteria through induction of reactive oxygen species and DNA damage. MTX also synergizes with vancomycin against VRE, rendering the resistant strains more permeable to MTX. In a murine wound infection model, single-dose MTX treatment effectively reduces VRE numbers, with further reduction when combined with vancomycin. Multiple MTX treatments accelerate wound closure. MTX also promotes macrophage recruitment and proinflammatory cytokine induction at the wound site and augments intracellular bacterial killing in macrophages by up-regulating the expression of lysosomal enzymes. These results show that MTX represents a promising bacterium- and host-targeted therapeutic for overcoming vancomycin resistance.
Assuntos
Enterococcus faecalis , Enterococos Resistentes à Vancomicina , Animais , Camundongos , Enterococcus faecalis/genética , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Mitoxantrona/farmacologia , Antibacterianos/farmacologia , Enterococos Resistentes à Vancomicina/genéticaAssuntos
Staphylococcus aureus Resistente à Meticilina , Neoplasias , Refugiados , Infecções Estafilocócicas , Enterococos Resistentes à Vancomicina , Criança , Humanos , Detecção Precoce de Câncer , Farmacorresistência Bacteriana Múltipla , Infecções Estafilocócicas/microbiologia , Inglaterra , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: To characterize the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and carbapenemase-producing Enterobacterales (CPE) co-colonization and to compare risk factors between healthcare facility types. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 3-year cross-sectional study among patients admitted to an acute-care hospital (ACH) and its 6 closely affiliated intermediate- and long-term care facilities (ILTCFs) in Singapore in June and July of 2014-2016. METHODS: Specimens were concurrently collected from nares, axillae, and groins for MRSA detection, and from rectum or stool for VRE and CPE detection. Co-colonization was defined as having >1 positive culture of MRSA/VRE/CPE. Multinomial logistic regression was performed to determine predictors of co-colonization. RESULTS: Of 5,456 patients recruited, 176 (3.2%) were co-colonized, with higher prevalence among patients in ITCFs (53 of 1,255, 4.2%) and the ACH (120 of 3,044, 3.9%) than LTCFs (3 of 1,157, 0.3%). MRSA/VRE was the most common type of co-colonization (162 of 5,456, 3.0%). Independent risk factors for co-colonization included male sex (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.37-2.80), prior antibiotic therapy of 1-3 days (OR, 10.39; 95% CI, 2.08-51.96), 4-7 days (OR, 4.89; 95% CI, 1.01-23.68), >7 days (OR, 11.72; 95% CI, 2.81-48.85), and having an open wound (OR, 2.34; 95% CI, 1.66-3.29). Additionally, we detected the synergistic interaction of length of stay >14 days and prior multidrug-resistant organism (MDRO) carriage on co-colonization. Having an emergency surgery was a significant predictor of co-colonization in ACH patients, and we detected a dose-response association between duration of antibiotic therapy and co-colonization in ILTCF patients. CONCLUSIONS: We observed common and differential risk factors for MDRO co-colonization across healthcare settings. This study has identified at-risk groups that merit intensive interventions, particularly patients with prior MDRO carriage and longer length of stay.
Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Enterococos Resistentes à Vancomicina , Humanos , Masculino , Vancomicina/farmacologia , Tempo de Internação , Estudos Transversais , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/complicações , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/complicações , PrevalênciaRESUMO
In this retrospective cohort of adult hematology-oncology and transplant patients, discontinuation of universal gloving did not result in significant changes in rates of central line-associated bloodstream infection, Clostridioides difficile infection, or vancomycin-resistant Enterococcus colonization. Active surveillance and subsequent isolation may be a viable alternative strategy to universal precautions.
Assuntos
Infecções por Clostridium , Infecção Hospitalar , Enterococos Resistentes à Vancomicina , Adulto , Humanos , Infecção Hospitalar/epidemiologia , Controle de Infecções/métodos , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Clostridioides , Estudos Retrospectivos , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controleRESUMO
In present study, we used Olea europaea leaf extract to biosynthesize in situ Copper Oxide nanocrystals (CuO @OVLe NCs) with powerful antibacterial and anti-cancer capabilities. Physio-chemical analyses, such as UV/Vis, FTIR, XRD, EDX, SEM, and TEM, were applied to characterize CuO @OVLe NCs. The UV/Vis spectrum demonstrated a strong peak at 345 nm. Furthermore, FTIR, XRD, and EDX validated the coating operation's contact with colloidal CuO @OVLe NCs. According to TEM and SEM analyses, CuO @OVLe NCs exhibited a spherical shape and uniform distribution of size with aggregation, for an average size of ~75 nm. The nanoparticles demonstrated a considerable antibacterial effect against E. faecium bacterial growth, as well as an increased inhibition rate in a dose-dependent manner on the MCF-7, PC3, and HpeG2 cancer cell lines and a decreased inhibition rate on WRL-68. Molecular docking and MD simulation were used to demonstrate the high binding affinity of a ligand (Oleuropein) toward the lectin receptor complex of the outer membrane to vancomycin-resistant E. faecium (VREfm) via amino acids (Leu 195, Thr 288, His 165, and Ser 196). Hence, our results expand the accessibility of OVLe's bioactive components as a promising natural source for the manufacture of physiologically active components and the creation of green biosynthesis of metal nanocrystals.