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Background Patients undergoing hematopoietic stem cell transplant (HSCT) require a central venous catheter (CVC) for their care. The presence of a CVC increases the risk of bloodstream infections (BSI). Central line associated bloodstream infections (CLABSI) are associated with increase morbidity, mortality and healthcare costs. Substantial effort is placed in the maintenance and disinfection of needless connectors (NC) with the goal to prevent CLABSI. Current guidelines don't specify the duration of mechanical friction that should be applied to NC prior to accessing a CVC. Our current practice is 30 seconds of scrubbing and 30 seconds of dry time with nurses collectively spending approximately a total of 120 hours/day scrubbing. The objective of this study was to evaluate the impact that length of mechanical friction has on NC disinfection. Methods Sixty sterile NC were used, divided in groups of ten. McFarland solution composed of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa was used to inoculate the NC for 30 minutes. One millimeter of sterile saline was used to flush the NC into a sterile tube and ten microliter loops were used to inoculate blood agar plates followed by use of spreaders for quantification. The first group was negative controls which were flushed after being removed from the package, the second group was positive controls with no scrubbing done prior to the flush. For the remaining 4 groups 2% chlorhexidine gluconate plus 70% alcohol pads were used to scrub the NC per routine practice for 15 seconds, 30 seconds, 45 seconds and 60 seconds. All the groups had the same drying time of 30 seconds. After 24 hours of incubation at 38 degrees Celsius positive cultures were identified and number of colonies on each plate were recorded. Ten nurses participated in the study scrubbing the hubs. Results All the negative controls were negative, 7/10 positive controls were positive with a mean of 127 CFU/ml. For the 3rd group 8/10 were positive with a mean of 171 CFU/ml. For the 4th group 6/10 were positive with a mean of 122 CFU/ml. For the 5th group 4/10 were positive with a mean of 55 CFU/ml and for the 6th group 3/10 were positive with a total of 15 CFU/ml. There was a statistically significant difference between positive and negative cultures in the 15 second group versus 60 second group (p = 0.02) but not between the 30 second versus the 60 second group (p=0.2). Three cultures were too numerous to count and were given a value of 1000 CFU/ml. Results do not appear to be dependent on who was scrubbing the NC. Conclusions Longer scrubbing time appears to decrease line contamination which can be translated into clinical practice. Results from a larger study with a total of 120 NC assessing different disinfecting solutions as well as drying time will be available by December 2018. [ABSTRACT FROM AUTHOR]

Background Blood stream infections (BSI) in hematopoietic stem cell transplant (HSCT) patients with central venous catheters may arise from translocation of bacteria through a non-intact gastrointestinal mucosa and are known as mucosal barrier injury–laboratory confirmed blood stream infections (MBI-LCBI). Central venous catheter maintenance care doesn't prevent MBI-LCB and currently there are no proven strategies to prevent bacteremia secondary to mucosal barrier injury. Gingivitis and periodontitis are features of the mucosal toxicity seen post-HSCT and are associated with BSI frequency. Xylitol is a non-fermentable polysaccharide that reduces dental caries, plaque accumulation, and oral disease progression by inhibiting bacterial growth and community development. We hypothesized that daily dental xylitol, in addition to current oral care practice, is effective at reducing gingivitis, periodontitis and BSI from oral organisms. Methods We performed a prospective randomized controlled trial to test our hypothesis. All patients received standard oral care and half were randomized to additionally receive daily xylitol. Oral exams were performed at baseline and at intervals for the first 28 days post-HSCT. Metagenomic shotgun sequencing of gingival samples was performed at these same intervals. For patients who develop BSI, whole genome sequencing of bacterial isolates is being performed to assess for genetic relatedness to corresponding strains present within the patient's oral microbiome preceding the infection. Results We enrolled 35 patients, 17 cases and 18 controls before ending the study early for efficacy. Five patients withdrew from the study (3 cases, 2 controls). Patients who received xylitol had a significantly lower rate of gingivitis, oral plaque and oral ulcers greater than 10 mm. There was a significant decrease in BSI from oral organisms in the first 30 days post HSCT in the xylitol group, 0/14 (0%) vs 5/16 (31%) (p = 0.04). Preliminary microbiome analysis showed decrease relative abundance of Candida albicans in patients receiving xylitol and individual patient analysis shows that xylitol may also impede Streptococcus mitis/oralis dominance in the oral microbiome. Additionally, we found that Staphylococcus aureus, a common cause of Central Line Associated Blood Stream Infection (CLABSI), was prominent in several gingival samples, suggesting BSI with Staphylococcus aureus may indeed be related to mucosal barrier injury. Conclusions The addition of xylitol to oral standard care appears to decrease BSI secondary to oral organisms, dental plaque, gingivitis and oral ulcerations in patients undergoing SCT. [ABSTRACT FROM AUTHOR]

Background Sleep is an essential biological function vital for physiological rest, healing and emotional well-being. Sleep disruption, defined as interruptions or alterations to the normal sleeping patterns, is commonly seen in patients and caregivers with lengthy hospital stays such as patients undergoing hematopoietic stem cell transplant (HSCT). Sleep disruption in the caregivers of hospitalized patients can lead to increased stress and fatigue, decrease quality of life and ultimately affect the caregiver ability to support their loved one. Methods Through a longitudinal observational cohort study, the quality and quantity of sleep in pediatric patients undergoing HSCT and their caregivers was studied; we identified a high level of sleep disturbance utilizing actigraphy and recounted poor sleep through qualitative assessments. We then performed a cross sectional focus group analysis of patients, caregivers and medical staff to identify the factors associated with poor sleep. The global aim of our quality improvement initiative was to improve sleep quality in HSCT patients and caregivers. The smart aim of our project was to decrease nighttime noise from 46 decibels (dB) (mean baseline data) to 38dB (WHO recommends night outside noise of less than 40dB) in a 6 month period and increase sleep efficacy from a mean of 60 % (combined patient and caregiver) to 90% in the following 6 month period. We worked on achieving this goal through an overnight nighttime sleep hygiene bundle to decrease sleep disruption along with reduction of the hallway nighttime noise (9pm-7am). Results The most common factors associated with sleep disruption were noisy room entries, overnight trash pulls, loud hallway noise and noisy hospital staff. A simplified failure mode analysis identified four main key drivers; reliable nighttime awareness system, quiet nighttime nursing system, unobtrusive nighttime cleaning process and nighttime awareness maintenance system. Several PDSA (plan-do-study-act) interventions for each key driver took place and were adapted. The overnight mean dB decreased to 42dB (9% reduction). Overnight noise spikes above 60dB have decreased from a mean of 271 spikes to a mean of 151 spikes (44% reduction). Percentage of sleep efficacy results and follow up of quantitative and qualitative sleep assessments of patients and caregivers will be available by February 2019. Conclusions With a quality improvement initiative, we identified factors that negatively impact sleep and performed interventions that successfully mitigate these factors, leading to improved quality of sleep in HSCT patients and their caregivers. [ABSTRACT FROM AUTHOR]

Background Bloodstream infections (BSI) cause significant morbidity and mortality following pediatric hematopoietic stem cell transplantation (HSCT) and are increasingly from multidrug-resistant pathogens. Most of these BSI pathogens arise from the intestines. Increased evidence demonstrates commensal gut anaerobes maintain host resistance from enteric infection, while loss of commensals increases host susceptibility. Antibiotic use reduces gut anaerobes and allows a compensatory increased pathogen burden that precedes BSI; BSI risk is related to colonization burden. Recent reports suggest fecal microbiota transplantation (FMT) can displace an enteric pathogens and broad-spectrum antibiotic resistance genes during restoration of a healthy microbiome. However, the impact of intestinal microbiota on colonization, transmission, and invasive MDR infections is poorly understood in children undergoing HSCT. Methods Using metagenomic shotgun sequencing (MSS) data of longitudinal stool samples from high-risk children, including 63 undergoing HSCT with 166 samples preceding BSI onset (n = 23), we developed a metagenomic-based infection risk index (IRI) from key microbiome features (scaled Brady-Curtis distance relative to healthy controls and relative anaerobe and pathogen abundance). Traditional cart data analysis was compared to advanced machine learning algorithms that consider microbiome distribution, longitudinal sampling, and feature selection. Results A metagenomic-derived IRI from our cohort identified children having up to an 8-fold increased BSI risk. Evaluation of these key microbiome features as a diagnostic screening test by traditional cart analysis accurately identified patients at-risk for BSI with 91% sensitivity using its negative likelihood ratio. However, its specificity of 51% prohibits targeting interventions to those at greatest risk (Figure 1). Therefore, advanced machine learning algorithms were used for metagenomic-derived BSI prediction. While training results suggest overfitting, its performance promises clinical utility with a sensitivity of 92% and specificity of 84% warranting optimization and validation in HSCT patients (Figure 2). Analysis during heterologous FMT interventions in 5 symptomatic high-risk children (including 1 HSCT patient) revealed a concomitant pathogen-dominated gut microbiome harboring a high burden of broad-spectrum antibiotic resistance genes prior to each FMT. Following FMT, we confirmed restoration of a healthy gut microbiome with abundant anaerobes had a low metagenomic-derived IRI in all cases (Figure 3). Conclusions The application of advanced machine learning to shotgun metagenomic data provides the resolution required for accurate BSI prediction to identify HSCT patients at greatest risk preceding an illness providing new opportunity for early FMT intervention to prevent BSI. [ABSTRACT FROM AUTHOR]

Background Transplant associated thrombotic microangiopathy (TMA) is a severe complication of stem cell transplant (SCT), characterized by endothelial damage leading to microangiopathic hemolytic anemia, thrombocytopenia and organ damage. Mild cases of TMA do not require treatment, but severe cases are associated with organ damage and mortality. Soluble suppression of tumorigenicity-2 (ST2) is a member of the interleukin 1 receptor family and has been associated with cardiac as well as endothelial injury. Elevated soluble terminal complement complex (sC5b-9) has recently been shown to be associated with high-risk TMA. We hypothesize that both complement activation (indicated by increased Sc5b9) and endothelial injury (indicated by increased ST2) occur early in the transplant process, setting up later tissue injury and organ damage, and these markers may be used to predict individuals at high-risk of later TMA, perhaps even before the start of the conditioning regimen. Methods We evaluated 276 consecutive pediatric allogeneic SCT patients at our center. Patients were diagnosed with high-risk TMA if they received eculizumab therapy and demonstrated laboratory and clinical markers of TMA on at least two consecutive tests, including evidence of complement activation, or the patient demonstrated evidence of microangiopathy on a tissue specimen. We compared early serum levels of ST2 and sC5b-9 between patients who later developed or did not develop high-risk TMA at two-time points: prior to the start of the chemotherapy/radiation (baseline) and 7 days after stem cell infusion (Day +7). Results 42 patients (15%) developed high-risk TMA requiring eculizumab at a median of 23 days (IQR: 10-46) post-SCT. Demographics were similar between the groups (Table 1). Patients with high-risk TMA were more likely to receive grafts from mismatched unrelated donors (52% vs. 29%, p=0.013). Patients with high-risk TMA had increased rates of acute GVHD at day 100 (33% vs 11%, p=0.001) and 1-year all-cause mortality (31 vs. 14%, 0.013). ST2 and sC5b-9 levels were significantly higher at baseline and day +7 in patients with high risk-TMA (Table 2). The area under the curve for high risk TMA using a log fold change in ST2 and sC5b-9 from baseline to day +7 was 0.802 (Figure 1). Discussion Plasma levels of sC5b-9 and ST2 are increased at baseline and 7 days after SCT in allogeneic recipients who develop high-risk TMA compared with those who do not. These data suggest complement activation and endothelial injury associated with high-risk TMA may occur before SCT and/or early on after the initiation of therapy. These markers could be used to identify high risk persons for increased screening and we are investigating whether genetic susceptibility, diagnosis of prior therapy might lead to increased baseline complement activity and pre-existing endothelial injury that might be ameliorated prior to start of transplant. [ABSTRACT FROM AUTHOR]