Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review

BACKGROUND: Vancomycin resistant enterococcus (VRE) is a major cause of nosocomial infections in the United States and may be associated with greater morbidity, mortality, and healthcare costs than vancomycin-susceptible enterococcus. Current guidelines for the control of VRE include prudent use of vancomycin. While vancomycin exposure appears to be a risk factor for VRE acquisition in individual patients, the effect of vancomycin usage at the population level is not known. We conducted a systematic review to determine the impact of reducing vancomycin use through prescribing interventions on the prevalence and incidence of VRE colonization and infection in hospitals within the United States. METHODS: To identify relevant studies, we searched three electronic databases, and hand searched selected journals. Thirteen studies from 12 articles met our inclusion criteria. Data were extracted and summarized for study setting, design, patient characteristics, types of intervention(s), and outcome measures. The relative risk, 95% confidence interval, and p-value associated with change in VRE acquisition pre- and post-vancomycin prescription interventions were calculated and compared. Heterogeneity in study results was formally explored by stratified analysis. RESULTS: No randomized clinical trials on this topic were found. Each of the 13 included studies used a quasi-experimental design of low hierarchy. Seven of the 13 studies reported statistically significant reductions in VRE acquisition following interventions, three studies reported no significant change, and three studies reported increases in VRE acquisition, one of which reported statistical significance. Results ranged from a reduction of 82.5% to an increase of 475%. Studies of specific wards, which included sicker patients, were more likely to report positive results than studies of an entire hospital including general inpatients (Fisher's exact test 0.029). The type of intervention, endemicity status, type of study design, and the duration of intervention were not found to significantly modify the results. Among the six studies that implemented vancomycin reduction strategies as the sole intervention, two of six (33%) found a significant reduction in VRE colonization and/or infection. In contrast, among studies implementing additional VRE control measures, five of seven (71%) reported a significant reduction. CONCLUSION: It was not possible to conclusively determine a potential role for vancomycin usage reductions in controlling VRE colonization and infection in hospitals in the United States. The effectiveness of such interventions and their sustainability remains poorly defined because of the heterogeneity and quality of studies. Future research using high-quality study designs and implementing vancomycin as the sole intervention are needed to answer this question

Prevalence of vancomycin-resistant Enterococcus fecal colonization among kidney transplant patients

BACKGROUND: End stage renal disease patients are at risk of Vancomycin-Resistant Enterococcus (VRE) infections. The first reports of VRE isolation were from hemodialysis patients. However, to date, VRE fecal colonization rates as well as associated risk factors in kidney transplant patients have not yet been established in prospective studies. METHODS: We collected one or two stool samples from 280 kidney transplant patients and analysed the prevalence of VRE and its associated risk factors. Patients were evaluated according to the post-transplant period: group 1, less than 30 days after transplantation (102 patients), group 2, one to 6 months after transplantation (73 patients) and group 3, more than 6 months after transplantation (105 patients). RESULTS: The overall prevalence rate of fecal VRE colonization was 13.6% (38/280), respectively 13.7% for Group 1, 15.1% for group 2 and 12.4% for group 3. E. faecium and E. faecalis comprised 50% of all VRE isolates. No immunologic variables were clearly correlated with VRE colonization and no infections related to VRE colonization were reported. CONCLUSION: Fecal VRE colonization rates in kidney transplant patients were as high as those reported for other high-risk groups, such as critical care and hemodialysis patients. This high rate of VRE colonization observed in kidney transplant recipients may have clinical relevance in infectious complications

Impact of digestive and oropharyngeal decontamination on the intestinal microbiota in ICU patients

Selective digestive microbial decontamination (SDD) is hypothesized to benefit patients in intensive care (ICU) by suppressing Gram-negative potential pathogens from the colon without affecting the anaerobic intestinal microbiota. The purpose of this study was to provide more insight to the effects of digestive tract and oropharyngeal decontamination on the intestinal microbiota by means of a prospective clinical trial in which faecal samples were collected from ICU patients for intestinal microbiota analysis. The faecal samples were collected from ICU patients enrolled in a multicentre trial to study the outcome of SDD and selective oral decontamination (SOD) in comparison with standard care (SC). Fluorescent in situ hybridization (FISH) was used to analyze the faecal microbiota. The numbers of bacteria from different bacterial groups were compared between the three regimens. The total counts of bacteria per gram faeces did not differ between regimens. The F. prausnitzii group of bacteria, representing an important group among intestinal microbiota, was significantly reduced in the SDD regimen compared to the SC and SOD. The Enterobacteriaceae were significantly suppressed during SDD compared to both SOD and SC; enterococci increased in SDD compared to both other regimens. The composition of the intestinal microbiota is importantly affected by SDD. The F. prausnitzii group was significantly suppressed during SDD. This group of microbiota is a predominant producer of butyrate, the main energy source for colonocytes. Reduction of this microbiota is an important trade-off while reducing gram-negative bacteria by SDD

Nutritional therapy and infectious diseases: a two-edged sword

The benefits and risks of nutritional therapies in the prevention and management of infectious diseases in the developed world are reviewed. There is strong evidence that early enteral feeding of patients prevents infections in a variety of traumatic and surgical illnesses. There is, however, little support for similar early feeding in medical illnesses. Parenteral nutrition increases the risk of infection when compared to enteral feeding or delayed nutrition. The use of gastric feedings appears to be as safe and effective as small bowel feedings. Dietary supplementation with glutamine appears to lower the risk of post-surgical infections and the ingestion of cranberry products has value in preventing urinary tract infections in women

Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations

Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic spine formation and synaptic stability. Using a Renilla-based sensor, we provide formal proof that inflammatory EVs transfer their miR-146a-5p cargo to neuron. By western blot and immunofluorescence analysis we show that vesicular miR-146a-5p suppresses Syt1 and Nlg1 expression in receiving neurons. Microglia-to-neuron miR-146a-5p transfer and Syt1 and Nlg1 downregulation do not occur when EV\ue2\u80\u93neuron contact is inhibited by cloaking vesicular phosphatidylserine residues and when neurons are exposed to EVs either depleted of miR-146a-5p, produced by pro-regenerative microglia, or storing inactive miR-146a-5p, produced by cells transfected with an anti-miR-146a-5p. Morphological analysis reveals that prolonged exposure to inflammatory EVs leads to significant decrease in dendritic spine density in hippocampal neurons in vivo and in primary culture, which is rescued in vitro by transfection of a miR-insensitive Nlg1 form. Dendritic spine loss is accompanied by a decrease in the density and strength of excitatory synapses, as indicated by reduced mEPSC frequency and amplitude. These findings link inflammatory microglia and enhanced EV production to loss of excitatory synapses, uncovering a previously unrecognized role for microglia-enriched miRNAs, released in association to EVs, in silencing of key synaptic genes