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There are no cohort studies describing outcomes of patients colonized with vancomycin-resistant enterococci (VRE) undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We therefore conducted a retrospective cohort study of 217 consecutive adults undergoing AHSCT at the Mayo Clinic (Rochester, MN, USA) from 1998 to 2004. We analyzed...
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The aim of study was to find out the potential pathogenic role of virulence factors elaborated by strains of vancomycin resistant enterococci (VRE) isolated from clinical samples and VRE colonizing the gastrointestinal tract of hospitalized patients.
Enterococci were isolated from various clinical samples and also from fecal specimens of colonized...
Background
There are no available studies on the duration and risk factors of vancomycin-resistant enterococci (VRE) carriage after hospital discharge. In this study we investigated the duration of colonization with VRE and the risk factors for prolonged carriage in the outpatient clinic after discharge from the hospital.
Methods
The study took pl...
Multidrug-resistant bacteria are major causes of nosocomial infections and are associated with considerable morbidity, mortality, and healthcare costs. Preventive strategies have therefore become increasingly important. Mathematical modeling has been widely used to understand the transmission dynamics of nosocomial infections and the quantitative e...
The impact of active surveillance of patients at risk for infection with vancomycin-resistant enterococci (VRE) was examined,
and VRE bacteremia rates and the degree of VRE clonality in 2 similar neighboring hospitals were compared. Hospital A did
not routinely screen patients for VRE rectal colonization; hospital B actively screened high-risk pati...
To determine whether total and antianaerobic antibiotic exposure increases the risk of room contamination among vancomycin-resistant enterococci (VRE)-colonized patients.
A 14-month study in 2 intensive care units at an academic tertiary care hospital in Boston, Massachusetts.
All patients who acquired VRE or were VRE-colonized on admission and who...
Citations
... Previous studies have proved that patients arrived for transplantation with microbiota compositions that were already distinct from those of healthy volunteer and that were characterized by loss of diversity and domination by single taxa [6,9,10], and the decrease in microbial diversity observed after transplantation persists for up to 1 year after transplantation [52]. Montassier et al. showed that the risk of bloodstream infections could be predicted by microbiota composition before HSCT [53] and that the risk of TRM could be predicted by the timing of exposure to antibiotics and by colonization with antibiotic-resistant bacteria before transplantation [54][55][56][57]. Thus, microbiota diversity can be early predictor of OS and TRM for allo-HSCT patients. ...
Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95% CI: 0.55–0.78), as well as decreased risk of transplant-related mortality (HR = 0.56, 95% CI: 0.41–0.76), and lower incidence of grade II-IV aGVHD (HR = 0.41, 95% CI: 0.27–0.63). Furthermore, higher abundance of Clostridiales was associated with a superior OS (HR = 0.40, 95% CI: 0.18–0.87), while higher abundance of Enterococcus (HR = 2.03, 95% CI: 1.55–2.65), γ-proteobacteria (HR = 2.82, 95% CI: 1.53–5.20), and Candida (HR = 3.80, 95% CI: 1.32–10.94) was an adverse prognostic factor for OS. Overall, this meta-analysis highlights the protective role of higher intestinal microbiota diversity on outcomes after allo-HSCT during both pre-transplant and post-transplant periods. Some specific microbiota can be useful in the identification of patients at risk of mortality, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.
... Initial empirical treatment does not include the coverage of vancomycin-resistant enterococci (VRE), penicillin-resistant viridans streptococci, and/or Candida species. VRE colonization is found to be predictive of VRE infection in several studies [95,[107][108][109][110][111], but enterococci are not covered in empirical antibiotic regimens for febrile neutropenia because they are of low pathogenicity. Therefore, the adjustment of antibiotic therapy because of VRE colonization is only recommended when infection with enterococci is highly suspected, or in critically ill patients (e.g., ICU admission, see ''Hemodynamically Unstable Neutropenic Patients/Neutropenic Patients Admitted to the ICU''). ...
Introduction:
This guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients.
Method:
The recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010-2020) and, where necessary, supplemented by expert-based advice.
Results:
For adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients.
Conclusion:
This guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia. The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin-tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended.
... KEYWORDS microbiome, vancomycin-resistant Enterococcus, colonization resistance, hospital-acquired infection V ancomycin-resistant Enterococcus (VRE) species are highly antibiotic-resistant bacteria, are a leading cause of health care-associated infections, and are classified as a serious public health threat by the Centers for Disease Control and Prevention (1,2). Colonization with VRE precedes infection (3,4), and molecular epidemiologic analyses show patient-to-patient hospital transmission is the primary means of spread (5). Preventing transmission between hospitalized patients is a significant challenge, and despite the widespread application of pathogen-targeted control measures (6), VRE remains prevalent in many hospitals (1,2). ...
The Centers for Disease Control and Prevention estimates that VRE causes an estimated 54,000 infections and 539 million dollars in attributable health care costs annually. Despite improvements in hand washing, environmental cleaning, and antibiotic use, VRE is still prevalent in many hospitals. There is a pressing need to better understand the processes by which patients acquire VRE. Multiple lines of evidence suggest that intestinal microbiota may help some patients resist VRE acquisition. In this large case-control study, we compared the 16S profile of intestinal microbiota on admission in patients that did and did not subsequently acquire VRE. The 16S profile did not predict subsequent VRE acquisition, in part due to rapid and dramatic change in the gut microbiome following hospitalization. However,
BlautiaEnterococcusLactobacillusEnterococcus
... The clinical significance of VRE colonization in hematopoietic stem cell transplantation (HSCT) is controversial. Zirakzadeh et al. [7] reported that pretransplant VRE colonization is associated with an increase in HSCT mortality, whereas VRE colonization on a prior admission was not an independent risk factor for bacteremia in a study reported by Kang et al. [8]. However, very few studies investigated whether donors with VRE colonization are suitable for solid organ transplantation, including kidney transplantation. ...
The colonization of vancomycin-resistant Enterococci before and after solid organ transplantation is associated with an increased risk of its infection. The prevalence of these bacterial colonies in renal transplant recipients are as high as that in intensive care unit patients. However, it is unclear whether donors with vancomycin-resistant Enterococci colonization can be considered in renal transplantation. Herein, we report a case wherein a kidney was transplanted from a deceased donor with vancomycin-resistant Enterococci colonies in urine and rectal swab. After transplant, the recipient had no vancomycin-resistant Enterococci infection and maintained relatively good renal function.
... This finding is consistent with previous work that showed that the risk of bloodstream infections could be predicted by microbiota composition before hematopoietic-cell transplantation 37 and that the risk of transplantation-related death could be predicted by the timing of exposure to antibiotics and by colonization with antibiotic-resistant bacteria before transplantation. 16,[38][39][40] Taken together, these results highlight two specific times relative to transplantation at which strategies to remediate or prevent microbiota injury could be evaluated in clinical trialsbefore transplantation and during the periengraftment period. ...
Background:
Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.
Methods:
The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death.
Results:
We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival.
Conclusions:
Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).
... This underscores the importance of enterococci as a possible cause of bacteremia in children with neuroblastoma, particularly in centers where empirical therapy is based on cephalosporins, which lack antienterococcal activity. Some studies, mainly those involving adults following HSCT, report high rates of mortality (18%-53%), severe sepsis (36%) and septic shock (12%) in adults following HSCT with EB. 2,5,8,10,18,21,33 Some, including those performed in children, as well as meta-analysis, demonstrate increased mortality in VRE compared with VSE infections. 4,5,18,21 VRE infection, mainly affecting severely ill patients, may be a marker for the critical condition of high-risk patients, although its direct contribution to the deterioration of the patient's condition cannot be excluded. ...
Background:
Data on enterococcal bacteremia (EB) in immunocompromised children are scarce. We aimed to describe EB in children with hematologic malignancies (HM), solid tumors and/or following allogeneic hematopoietic stem cell transplantation (HSCT) and analyze their ampicillin and vancomycin resistance.
Methods:
We conducted an observational retrospective study in the tertiary-care Hadassah University Medical Center (2001-2015). We collected demographic, clinical and laboratory data on EB and compared ampicillin and vancomycin sensitive with resistant episodes.
Results:
Fifty-six of 1123 children developed 74 episodes of EB; 62.1% Enterococcus faecium, 36.5% Enterococcus faecalis; and 1.4% Enterococcus gallinarum. EB developed in 12.1% of HSCT patients, 5.1% of HM, 6.3% of neuroblastoma and 1.0% of other solid tumors patients. Of these episodes, 85.1% were nosocomial, and 71.6% developed while on antibiotic therapy. Resistance rates were: to ampicillin, 57.6%; to vancomycin (vancomycin-resistant enterococci), 21.6%; and higher rates among E. faecium. Among vancomycin-resistant enterococci, 1 of 16 was linezolid and 2 of 10 daptomycin resistant. Overall 7- and 30-day mortality rates were 2.7% and 5.4%, respectively. Thirty-day mortality was 18.2% in recurrent episodes and 0% in the first-time EB episodes (P = 0.006). In multivariate analysis, high treatment intensity was associated with ampicillin resistance [odds ratio (OR) = 3.18, 95% confidence interval (CI): 1.31-9.12], prior penicillin exposure (OR = 7.50, 95% CI: 1.41-39.81) and breakthrough on vancomycin (OR = 18.83, 95% CI: 3.31-101.14) with vancomycin resistance.
Conclusions:
EB occurs mainly as a nosocomial infection in children receiving high-intensity chemotherapy, especially in those with neuroblastoma, HM and following HSCT. Antibiotic resistance is common. Vancomycin resistance can occur regardless of previous vancomycin use. Prognosis in immunocompromised children with EB is better than previously reported. Recurrent EB is associated with increased mortality.
... This finding is consistent with previous work that showed that the risk of bloodstream infections could be predicted by microbiota composition before hematopoietic-cell transplantation 37 and that the risk of transplantation-related death could be predicted by the timing of exposure to antibiotics and by colonization with antibioticresistant bacteria before transplantation. 16,[38][39][40] Taken together, these results highlight two specific times relative to transplantation at which strategies to remediate or prevent microbiota injury could be evaluated in clinical trials -be-fore transplantation and during the periengraftment period. ...
7015
Background: Relationships between microbiota composition and clinical outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) have been described in single-center studies. Geographic variations in human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. We report the first multi-center study of the intestinal microbiota in allo-HCT. Methods: Intestinal communities in 8,768 fecal samples from 1,362 allo-HCT patients at 4 centers on 3 continents were profiled by 16S sequencing. Associations between microbiota composition and clinical outcomes were analyzed with proportional-hazards analysis in an observational study. Results: We observed reproducible patterns of microbiota injury characterized by loss of diversity and domination by single taxa. Low diversity in the neutrophil engraftment period was reproducibly associated with increased risk of death (multivariate HR 0.48 [0.30-0.77] p = 0.002 in the largest cohort). These reductions in OS were in part due to an increased risk of transplant-related mortality and graft-vs-host disease. Baseline pre-HCT samples already bore evidence of microbiome disruption; low diversity prior to transplantation was associated with poor survival. A bacterial-composition risk score that was trained in one cohort predicted mortality in the other three cohorts (multivariate HR 1.42 [1.04-1.93] p = 0.03), indicating that not only a diversity metric but also a signature of specific bacterial abundances is informative about post-HCT mortality risk across independent institutions. Conclusions: We demonstrate a relationship between microbiota and survival after allo-HCT that is independent of transplant center and geographic location. The diversity of clinical practices across institutions imposed significant heterogeneity in the study, yet we observed reproducible microbiota injury patterns and associations with outcomes. This concordance suggests that approaches to manipulate the intestinal microbiota in allo-HCT may be generalizable.
... 6 Correspondingly, the prevalence of VRE colonization in allo-HSCT recipients is 16%-40%. [7][8][9][10] As severe neutropenia during transplantation leads to an increased susceptibility to infections including VRE bacteremia, 11,12 VRE colonization highly predisposes to later invasive VRE infections. Therefore, colonization with VRE may be used as a prediction marker for VRE bloodstream infection. ...
... 13,14 Recently, we published that patients colonized with gram-positive cocci (VRE and methicillin-resistant Staphylococcus aureus) had a significantly lower overall survival (OS) than patients tested negative for colonization. 15 It is well described that VRE colonization during allo-HSCT is associated with a reduced OS and an increased incidence of nonrelapse mortality most likely due to infections, 7,10,15 and different timepoints of VRE colonization before and during allo-HSCT may have a different impact on patient survival. 16 To identify the timepoints that are most significant for patient survival and to clarify whether the status of positive VRE colonization can be lost and whether only newly or also previous colonization might act as a predictor of increased mortality, we reanalyzed our previously published and now extended patient cohort. ...
Background
In haematology and oncology, in particular in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT), VRE colonization rates are high due to previous hospital stays and preceding antibiotic treatment and colonized patients have a lower overall survival (OS).
Objective
We reanalysed our previously published cohort, to unravel which colonization timepoints before and during allo‐HSCT might be predictive for the subsequent outcome.
Patients and methods
We report about 268 patients with acute myeloid leukemia receiving an allo‐HSCT between 2006 and 2016.
Results
We identified 129 never‐colonized patients, 15 previously colonized patients (positive only before admission for allo‐HSCT), 41 persistently colonized patients (positive before and at admission for allo‐HSCT) and 83 newly colonized patients (positive only during allo‐HSCT). Persistently and newly colonized patients had a worse 60 months OS due to increased incidence of NRM than never‐colonized patients (OS: never‐colonized: 61.0% vs. persistently colonized: 43.5%; p=0.023 vs. newly colonized: 45.6%; p=0.046). In contrast, OS and NRM of never‐colonized and previously colonized patients as well as between persistently and newly colonized patients were similar.
Conclusion
Patients can lose their VRE colonization status and acquisition of VRE during inpatient stay for allo‐HSCT decreases survival to a similar extend as persistent colonization.
This article is protected by copyright. All rights reserved.
... However, there is controversy in the literature with regard to the impact of MDRO colonization on the outcome of patients who undergo allo-HSCT. [12][13][14][15] Recently, we demonstrated that the detection of MDRO colonization was strongly associated with worse survival compared with noncolonized patients. 16 Therefore, in the current study, we retrospectively assessed outcomes of patients with AML after allo-HSCT at our institution and investigated whether MDRO colonization affected outcomes after allo-HSCT because of infectious-related death. ...
... Published data on VRE colonization during allo-HSCT vary from 16% to 36%. 14,15,29 We identified an overall VRE colonization rate of 46% (122 of 264 patients). These differences in VRE colonization prevalence might be explained by the underlying diseases and their pretransplantation treatment regimens, and, consequently, by differences in the administration of prophylactic and therapeutic anti-infective drugs like fluoroquinolones, which are a known risk factor for VRE colonization. ...
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.
... However, available epidemiological evidence remains conflicted regarding the precise relationships between pre-HSCT VRE colonization, HSCT-associated VRE bacteremia, and mortality. Prior studies reveal differing results as to whether pre-HSCT VRE colonization is a risk factor for HSCT-associated VRE bacteremia [1][2][3], whether pre-HSCT VRE colonization predicts increased HSCT mortality [3,4], and whether HSCT-associated VRE bacteremia itself causes an increase in HSCT death rates [4][5][6][7]. ...
... However, available epidemiological evidence remains conflicted regarding the precise relationships between pre-HSCT VRE colonization, HSCT-associated VRE bacteremia, and mortality. Prior studies reveal differing results as to whether pre-HSCT VRE colonization is a risk factor for HSCT-associated VRE bacteremia [1][2][3], whether pre-HSCT VRE colonization predicts increased HSCT mortality [3,4], and whether HSCT-associated VRE bacteremia itself causes an increase in HSCT death rates [4][5][6][7]. ...
... Our study examined a relatively homogenous cohort of 109 patients, all of whom had had multiple surveillance stool cultures before the screening culture performed at HSCT admission. Our results show that patients with detected VRE colonization before HSCT are a distinct subgroup of HSCT recipients who, unlike the finding of Kang et al. [3], have a higher incidence of HSCT-associated VRE bacteremia, and, unlike the conclusion of Zirakzadeh et al. [4], have no decrease in overall survival. We found that pre-HSCT colonization is primarily related to the number of pre-HSCT inpatient days. ...
The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admissions for leukemia and HSCT. One third of evaluable patients colonized pre-HSCT were VRE culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Post-engraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe GVHD and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization pre-HSCT and at HSCT, between pre-engraftment and post-engraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.
