Approaches to vancomycin-resistant enterococci

PURPOSE OF REVIEW: This article reviews recent publications regarding new antimicrobial drugs for the treatment of vancomycin-resistant enterococci. RECENT FINDINGS: Newer drugs against vancomycin-resistant enterococci are now available or will soon be available. Quinupristin-dalfopristin, a streptogramin, and linezolid, an oxazolidinone, are effective and safe but only bacteriostatic against enterococi. Bacterial isolates resistant to either antibiotic have been described. Daptomycin, a lipopeptide antimicrobial, has good in-vitro bactericidal activity against enterococci, but very limited clinical data exist regarding the treatment of serious enterococcal infection with this compound. Ramoplanin, the first glycolipodepsipeptide antimicrobial in clinical trials, is not systemically absorbed after oral administration, and is being evaluated for the prevention of bloodstream infection in patients colonized with vancomycin-resistant enterococci. Oritavancin and dalbavancin (both glycopeptides) and tigecycline (a monocycline derivative) are being evaluated in phase II and III trials and are not yet commercially available. SUMMARY: Treatment of vancomycin-resistant enterococci continues to be problematical although these new drugs offer some hope. The rational use of antibiotics, strict guidelines for the use of new compounds, and adherence to infection control practices continue to be essential components of the management of vancomycin-resistant enterococci colonization and infection.     

Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies

Background

In patients with haematological or oncological malignancies, we aimed to assess the rate of intestinal colonisation and blood stream infections (BSI) with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and vancomycin-resistant enterococci (VRE), mortality and risk factors associated with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE in combination with adapted empiric treatment of febrile neutropenia.

Methods

Within 72?h of admission to our department, an ESBLE and VRE screening stool sample was collected. In the case of neutropenic fever, blood cultures were drawn. Data of all admitted patients were prospectively documented. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for progression from intestinal colonisation to BSI.

Results

During the study period, 1,805 stool samples were obtained from 513 patients during 1,012 inpatient stays, and 2,766 blood cultures were obtained from 578 patients during 1,091 inpatient stays. Ninety (17.5?%) of these patients were colonised with ESBLE and 51 (9.9?%) with VRE. Proportions of 40?% (36/90) of ESBLE and 61?% (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6?%) ESBLE-colonised patients and 1/51 (2?%) VRE-colonised patients developed BSI with the respective organism. None of these patients died after receiving early appropriate empiric antibiotics based on colonisation status. Colonisation with ESBLE or VRE was associated with increased risk ratios (RR) towards developing ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89?C7.04] and VRE BSI (RR 10.2, 95 % CI: 7.87?C13.32), respectively. Acute myelogenous leukaemia and prior treatment with platinum analogues or quinolones were identified as independent risk factors for ESBLE BSI in colonised patients.

Conclusions

Intestinal ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology patients in combination with directed empiric treatment may reduce ESBLE BSI-related mortality.     

The effect of active surveillance for vancomycin-resistant enterococci in high-risk units on vancomycin-resistant enterococci incidence hospital-wide

BACKGROUND: Vancomycin-resistant enterococci (VRE) have become a major cause of nosocomial infections and are now endemic in many geographic areas. The aim of this study was to describe the effect of active surveillance for patients with VRE in high-risk units on the VRE incidence rate hospital-wide. METHODS: We determined 4 time periods based on the intervention of active surveillance: preactive surveillance (period 1), active surveillance (period 2), no active surveillance (period 3), and reinstutition of active surveillance (period 4). VRE incidence rates based on first clinical culture for VRE per 10,000 patient days for each of these periods and incidence rate ratios were then calculated. RESULTS: Active surveillance in high-risk units was associated with a significant reduction in VRE incidence hospital-wide in 2 of the 3 comparisons made. The incidence rate ratio when comparing the first period of active surveillance (period 2) to the preactive surveillance period (period 1) was 0.63 (95% CI, 0.38-1.1); it was 0.36 (95% CI, 0.23-0.55) when comparing the first period of active surveillance (period 2) to the subsequent period (period 3) and 0.68 (95% CI, 0.54-0.85) when comparing the second period of active surveillance (period 4) to the prior period without active surveillance periods. CONCLUSIONS: Active surveillance culturing for VRE in the high risk-units prevented further VRE transmission, as evidenced by a significant increase in hospital-wide incidence rates when active surveillance was discontinued and a significant decrease in incidence rates when it was restarted.     

The epidemiology of vancomycin-resistant enterococci

Major differences in the epidemiology of vanA carrying enterococci exist between Europe and the USA, where these organisms have been well investigated. These differences are probably related to the differences in antibiotic use in humans and animals in both continents, but more research is needed before firm conclusions can be drawn.     

Increase of the number of vancomycin resistant enterococci (VRE) isolated in Helsinki,Finland

The emergence of hospital acquired infections with bacteria resistant to antimicrobials such as vancomycin resistant enterococci (VRE) has become a worldwide concern. In hospitals in the United States, VRE have spread quickly and currently account for eve     

Nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VRE) ST796, Switzerland, 2017 to 2020

A large clonal outbreak caused by vancomycin-resistant Enterococcus faecium (VRE) affected the Bern University Hospital group from the end of December 2017 until July 2020. We describe the characteristics of the outbreak and the bundle of infection prevention and control (IPC) measures implemented. The outbreak was first recognised when two concomitant cases of VRE bloodstream infection were identified on the oncology ward. During 32 months, 518 patients in the 1,300-bed hospital group were identified as vanB VRE carriers. Eighteen (3.5%) patients developed an invasive infection, of whom seven had bacteraemia. In 2018, a subset of 328 isolates were analysed by whole genome sequencing, 312 of which were identified as sequence type (ST) 796. The initial IPC measures were implemented with a focus on the affected wards. However, in June 2018, ST796 caused another increase in cases, and the management strategy was intensified and escalated to a hospital-wide level. The clinical impact of this large nosocomial VRE outbreak with the emergent clone ST796 was modest. A hospital-wide approach with a multimodal IPC bundle was successful against this highly transmissible strain.     

Health and economic outcomes of vancomycin-resistant enterococci

BACKGROUND: The health and economic impact of vancomycin-resistant enterococci has not been quantified. METHODS: A retrospective matched cohort study was conducted comparing the outcomes of patients with vancomycin-resistant enterococci (cases) with those of control subjects matched for length of hospital stay until inclusion in the cohort, hospital location, and calendar date. The propensity to be a vancomycin-resistant enterococci case was modeled based on patient characteristics, and included in multivariable models to adjust for confounding. Analyses included the following: (1) conditional logistic regression for mortality, surgery, intensive care unit admission, and discharge to long-term care; (2) linear regression for the logarithm of cost; and (3) accelerated failure time model for length of stay. RESULTS: A total of 233 cases were compared with 647 controls. Groups were similar in age (mean, 62 years), sex (female, 47%), and length of stay before inclusion in the cohort (mean, 8.1 days), but differed in primary diagnosis and comorbidities, past infection or colonization with methicillin sodium-resistant Staphylococcus aureus or Clostridium difficile, and treatment with cephalosporins or metronidazole. These variables were included in the propensity score, which had good to excellent prediction. Outcomes for cases vs controls and adjusted risks (relative risks [RRs]) were as follows: (1) case fatality rate, 17% vs 6% (RR, 2.13; P =.04); (2) length of stay after inclusion in the cohort, 15.1 vs 8.5 days (RR, 1.73; P<.001); (3) hospital costs, $52 449 vs $31 915 (RR, 1.40; P<.001); (4) surgery after inclusion in the cohort, 18% vs 10% (RR, 2.74; P =.001); (5) intensive care unit admission after inclusion in the cohort, 25% vs 14% (RR, 3.47; P<.001); and (6) transfer to an institution, 51% vs 35% (RR, 2.01; P =.001). CONCLUSION: Compared with a matched hospital population, a population with vancomycin-resistant enterococci was associated with severe adverse outcomes: increased mortality, morbidity, and costs.     

Beta-lactam antibiotics and gastrointestinal colonization with vancomycin-resistant enterococci

We studied the effect of different subcutaneously administered beta-lactam antibiotics on the establishment of gastrointestinal colonization by vancomycin-resistant Enterococcus faecium C68 in a mouse model. Aztreonam, cefazolin, cefepime, and, to a lesser extent, ceftazidime, which neither have significant antienterococcal activity nor are secreted into human bile at high concentrations, did not promote significant vancomycin-resistant enterococci (VRE) colonization. Piperacillin-tazobactam, which has antienterococcal activity and is secreted in human bile at high concentrations, inhibited colonization after limited exposure to the inoculum but was associated with progressively increased VRE colony counts in stool samples after repeated exposure to the VRE inoculum. Ceftriaxone and cefotetan, which lack antienterococcal activity but are secreted into human bile at high concentrations, were associated with rapid and high-level colonization. These data suggest that the risk of VRE colonization varies during exposure to different beta-lactam antimicrobial agents and that the risk is related to biliary concentration and antienterococcal activity of the specific beta-lactam.     

Prevalence of vancomycin-resistant enterococci in hospital and community environment

Aim of the study: The presented study aimed at determining the prevalence of vancomycin-resistant enterococci (VRE) in rectal swabs taken from both patients in the Teaching Hospital in Olomouc (THO), Czech Republic, and subjects from the community setting of the hospital's catchment area. Materials and methods: Between July 1, 2002 and July 1, 2003, rectal swabs were taken from the THO patients as well as individuals from the community catchment area to be utilized for isolating and identifying enterococci and their suscetibility to antibiotics. Vancomycin resistance phenotypes were verified by PCR detection of vanA, vanB, vanC1 and vanC2 genes. A molecular biology analysis was performed in VanA Enterococcus faecium strains. To determine the relationship of strains, macrorestriction analysis of the total chromosomal DNA digested with SmaI restriction endonuclease was used. Results: During the observed period, 2,157 rectal swabs from the hospitalized patients and 4,874 rectal swabs from the subjects in community setting were examined. In total, 27 VRE of hospital origin and 13 community-population strains were isolated. The prevalence of VRE in the gastrointestinal tract was 2.3 % in the hospitalized patients and 0.6 % in the community subjects. The prevailing strains were Enterococcus faecium VanA (70.4 %) in the VRE of hospital origin and Enterococcus gallinarum VanC (46.2 %) in the community VRE. Mutual comparison between the hospital and community VRE showed no similarity. Conclusion: In the Czech Republic, VRE were proved both in community and hospital settings. Their prevalence in rectal swabs is low and does not exceed the values reported in other European countries. The author describes the chief characteristics of the most important quinolone antibiotics, including preparations either in their development stage or whose development has been prematurely interrupted because of adverse side-effects. The list includes all preparations that are or were temporarily registered in the Czech Republic.     

Improving the assessment of vancomycin-resistant enterococci by routine screening

BACKGROUND: As infection with vancomycin-resistant enterococci (VRE) increases in hospitals, knowledge about VRE reservoirs and improved accuracy of epidemiologic measures are needed. Many assessments underestimate incidence by including prevalent carriers in at-risk populations. Routine surveillance cultures can substantially improve prevalence and incidence estimates, and assessing the range of improvement across diverse units is important. METHODS: We performed a retrospective cohort study using accurate at-risk populations to evaluate the range of benefit of admission and weekly surveillance cultures in detecting unrecognized VRE in 14 patient-care units. RESULTS: We assessed 165 unit-months. The admission prevalence of VRE was 2.2%-27.2%, with admission surveillance providing 2.2-17-fold increased detection. Medical units were significantly more likely to admit VRE carriers than were surgical units. Monthly incidence was 0.8%-9.7%, with weekly surveillance providing 3.3-15.4-fold increased detection. The common practice of reporting incidence using the total number of patients, rather than patients at risk, underestimated incidence by one-third. Overall, routine surveillance prevented the misclassification of 43.0% (unit range, 0%-85.7%) of "incident" carriers on the basis of clinical cultures alone and increased VRE precaution days by 2.4-fold (unit range, 2.0-2.6-fold). CONCLUSIONS: Routine surveillance markedly increases the detection of VRE, despite variability across patient-care units. Correct denominators prevent the substantial underestimation of incidence.     

Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course

Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant.