Vancomycin-resistant Enterococci Acquisition Research Articles

Antimicrobial Use and Carbapenem-Resistant Enterobacterales in Korea: A Nationwide Case-Control Study With Propensity Score Matching.

Nationwide research on the association between carbapenem-resistant Enterobacterales (CREs) and antibiotic use is limited. This nested case-control study analyzed Korean National Health Insurance claims data from April 2017 to April 2019. Based on the occurrence of CRE, hospitalized patients aged ≥ 18 years were classified into CRE (cases) and control groups. Propensity scores based on age, sex, modified Charlson comorbidity score, insurance type, long-term care facility, intensive care unit stay, and acquisition of vancomycin-resistant Enterococci were used to match the case and control groups (1:3). After matching, the study included 6,476 participants (1,619 cases and 4,857 controls). Multivariable logistic regression analysis revealed that the utilization of broad-spectrum antibiotics, such as piperacillin/tazobactam (adjusted odds ratio [aOR], 2.178; 95% confidence interval [CI], 1.829-2.594), third/fourth generation cephalosporins (aOR, 1.764; 95% CI, 1.514-2.056), and carbapenems (aOR, 1.775; 95% CI, 1.454-2.165), as well as the presence of comorbidities (diabetes [aOR, 1.237; 95% CI, 1.061-1.443], hemiplegia or paraplegia [aOR, 1.370; 95% CI, 1.119-1.679], kidney disease [aOR, 1.312; 95% CI, 1.105-1.559], and liver disease [aOR, 1.431; 95% CI, 1.073-1.908]), were significantly associated with the development of CRE. Additionally, the CRE group had higher mortality (8.33 vs. 3.32 incidence rate per 100 person-months, P < 0.001) and a total cost of healthcare utilization per person-month (15,325,491 ± 23,587,378 vs. 5,263,373 ± 14,070,118 KRW, P < 0.001) than the control group. The utilization of broad-spectrum antibiotics and the presence of comorbidities are associated with increasing development of CRE. This study emphasizes the importance of antimicrobial stewardship in reducing broad-spectrum antibiotic use and CRE disease burden in Korea.

VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Daptomycin-Resistant Enterococcus Bacteremia Is Associated With Prior Daptomycin Use and Increased Mortality After Liver Transplantation.

BackgroundRisk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact of daptomycin-resistant Enterococcus (DRE) in this patient population.MethodsWe conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within 1 year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest.ResultsWe identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total intensive care unit days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within 1 year of transplantation (adjusted odds ratio [aOR], 2.648; 95% CI, 1.025–6.840; P = .044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR, 30.62; 95% CI, 10.087–92.955; P < .001).ConclusionsIn this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared with VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

1221. Genomic Factors Affecting the Efficacy of Antimicrobial Therapy in Daptomycin-, Linezolid-, Vancomycin-Resistant Enterococcus faecium (DLVRE)

BackgroundNosocomial acquisition of vancomycin-resistant Enterococcus (VRE) is one of the most challenging problems in healthcare. As Enterococcus isolates are increasingly resistant to vancomycin, clinicians now rely on alternative antimicrobial therapies including linezolid and daptomycin (DAP) to treat infections. For multidrug-resistant (MDR) VRE, combination therapy with beta-lactams and daptomycin has been shown to be effective. MethodsFollowing initiation of empiric DAP and ceftaroline (CPT) for an MDR E. faecium bloodstream infection (VRE_001), we aimed to determine if there existed in vitro synergy between both agents that supported their clinical use. Combination synergy testing was performed using E-test strips and minimal inhibitory concentrations (MICs) were read at 24 hours. For whole genome sequence-based analysis (WGS), genomic DNA from VRE_001 was used for both short read (Illumina MiSeq) and long-read sequencing (MinION, Nanopore). The complete genome was assembled and the NCBI AMRFinderPlus program used to identify known resistance mechanisms. ResultsOriginal MICs of VRE_001 from the clinical microbiology laboratory at Northwestern Memorial revealed an MDR E. faecium (Table 1). Combination synergy testing in the experimental laboratory revealed only modest amounts of synergy between CPT and DAP (Table 2). Following WGS, VRE_001 was identified as an ST-584 E. faecium with a 3.2 Mbp genome, including a single chromosome and five plasmids. WGS analysis revealed several mechanisms of antimicrobial resistance (Table 3) genetically supporting the observed MDR-DLVRE phenotype. ConclusionOur investigational antimicrobial testing allowed for real-time in vitro analysis of synergistic MICs in a case of DLVRE bacteremia. Despite the fact that in vitro testing of CPT and DAP did not support the clinical usage of combination antimicrobial therapy, the patient cleared their blood cultures. WGS of VRE_001 revealed a plethora of antimicrobial resistance mechanisms including three mutations that explain high levels of DAP resistance. Synergy testing is not routinely available in most clinical laboratories, but rapid implementation of investigational MIC testing paired with genomic analysis may one day successfully support real-time clinical decision making.Disclosures All Authors: No reported disclosures

Real-world experience of how chlorhexidine bathing affects the acquisition and incidence of vancomycin-resistant enterococci (VRE) in a medical intensive care unit with VRE endemicity: a prospective interrupted time-series study

BackgroundCritically ill patients in intensive care units (ICUs) often acquire opportunistic infections or are colonized by vancomycin-resistant enterococci (VRE), which limits therapeutic options and results in high case-fatality rates. In clinical practice, the beneficial effects of universal chlorhexidine gluconate (CHG) bathing on the control of VRE remain unclear. This study aimed to investigate whether 2% CHG daily bathing reduced the acquisition of VRE in the setting of a medical ICU (MICU) with VRE endemicity.MethodsThis quasi-experimental intervention study was conducted in a 23-bed MICU of a tertiary care hospital in Korea from September 2016 to December 2017. In a prospective, interrupted time-series analysis (ITS) with a 6-month CHG bathing intervention, we compared the acquisition and incidence of VRE and the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter baumannii (CRAB) between the pre-intervention and intervention periods. The primary and secondary outcomes were a change in the acquisition of VRE and incidence of VRE, MRSA, or CRAB between the two periods, respectively.ResultsAll the adult patients admitted to the MICU were enrolled in the pre-intervention (n = 259) and intervention (n = 242). The overall CHG daily bathing compliance rate was 72.5%. In the ITS, there was a significant intervention effect with a 58% decrease in VRE acquisition (95% CI 7.1–82.1%, p = 0.038) following the intervention. However, there was no significant intervention effects on the incidence trend of VRE, MRSA, and CRAB determined by clinical culture between the pre-intervention and intervention periods.ConclusionIn this real-world study, we concluded that daily bathing with CHG may be an effective measure to reduce VRE cross-transmission among patients in MICU with a high VRE endemicity.

Impact of Clostridioides difficile Therapy on Nosocomial Acquisition of Vancomycin-Resistant Enterococci.

Vancomycin is frequently used for the treatment of C. difficile infections (CDI). There are concerns that this might increase the risk of selecting vancomycin resistant enterococci (VRE). Here, we evaluated whether there is an increased risk of VRE acquisition following vancomycin for CDI specific treatment. Patients with CDI, metronidazole, or oral vancomycin treatment and without preexisting VRE were monitored for VRE acquisition. VRE isolates from patients with acquired and preexisting colonization were collected and subjected to whole genome sequencing. In total, 281 patients (median age 56 years, 54% of the male sex) presented with toxin positive C. difficile. Of them, 170 patients met the inclusion criteria, comprising 37 patients treated with metronidazole and 133 treated with oral vancomycin. In total, 14 patients meeting the inclusion criteria acquired VRE (vancomycin: n = 11; metronidazole: n = 3). Statistical analysis revealed no significant differences between both VRE acquisition rates. Genetic comparison of detected VRE isolates resulted in eight clusters of closely related genotypes comprising acquired and preexisting strains. Our results suggest that vancomycin and metronidazole likewise increase the risk of VRE acquisition. Genetic comparison indicates that VRE acquisition is a result of both antibiotic selection and pathogen transmission.

4425 Anibiotic-Resistant Organism Acquisition in Nursing Facility Patients

OBJECTIVES/GOALS: We investigated the association between gut microbiota features in newly admitted nursing facility (NF) patients and the acquisition of vancomycin-resistant Enterococcus (VRE) and/or resistant Gram-negative bacteria (rGNB) within 14 days. METHODS/STUDY POPULATION: Patients were recruited at 6 Michigan NFs from 09/16-08/18. VRE or rGNB colonization status was determined by culture swabs collected from multiple body sites at enrolment, day 7, and day 14. Our analysis focused on patients with no colonization at baseline, a perirectal swab collected at baseline, and at least one follow-up visit. The V4 hypervariable region of the 16S rRNA gene from bacterial DNA in each sample was PCR-amplified and sequenced on the MiSeq platform. Sequencing results were then processed with the mothur bioinformatics pipeline to classify bacterial taxa present in each sample. Taxa typically associated with the skin microbiota were removed. The primary outcome was acquisition of VRE and/or rGNB within 14 days. Exposures of interest included patient and microbiota characteristics. RESULTS/ANTICIPATED RESULTS: Among 61 patients, 18 (30%) acquired AROs within 14 days of enrolment (3 VRE, 13 rGNB, 2 both) (Table 1). The baseline microbiota features differed significantly in those who acquired a new ARO. Of the major 8 phyla found across samples, patients who acquired an ARO were depleted in the number of phyla present (5.74 ± 1.20 vs 5.06 ± 1.43; p = 0.037) (Fig. 1). The log10-transformed relative abundance of Enterococcus was enriched in patients who acquired an ARO (−0.32 ± 1.47) compared to those who did not (−1.68 ± 1.76; p = 0.021) (Fig. 2). Patients who did not acquire an ARO tended to harbour more butyrate-producing bacterial taxa and strict anaerobes, although the differences were not statistically significant (relative abundance of butyrate producer: 29.49 ± 22.09 vs 22.05 ± 17.76; anaerobes: 64.78 ± 23.54 vs 53.68 ± 27.61). DISCUSSION/SIGNIFICANCE OF IMPACT: Microbiota metrics calculated from perirectal samples are predictive of ARO acquisition. The clinical utility of perirectal samples thus warrants further assessment.

The Role of Healthcare Worker-Mediated Contact Networks in the Transmission of Vancomycin-Resistant Enterococci.

BackgroundUser- and time-stamped data from hospital electronic health records (EHRs) present opportunities to evaluate how healthcare worker (HCW)-mediated contact networks impact transmission of multidrug-resistant pathogens, such as vancomycin-resistant enterococci (VRE).MethodsThis is a retrospective analysis of incident acquisitions of VRE between July 1, 2016 and June 30, 2018. Clinical and demographic patient data were extracted from the hospital EHR system, including all recorded HCW contacts with patients. Contacts by an HCW with 2 different patients within 1 hour was considered a “connection”. Incident VRE acquisition was determined by positive clinical or surveillance cultures collected ≥72 hours after a negative surveillance culture.ResultsThere were 2952 hospitalizations by 2364 patients who had ≥2 VRE surveillance swabs, 112 (4.7%) patients of which had incident nosocomial acquisitions. Patients had a median of 24 (interquartile range [IQR], 18–33) recorded HCW contacts per day, 9 (IQR, 5–16) of which, or approximately 40%, were connections that occurred <1 hour after another patient contact. Patients that acquired VRE had a higher average number of daily connections to VRE-positive patients (3.1 [standard deviation {SD}, 2.4] versus 2.0 [SD, 2.1]). Controlling for other risk factors, connection to a VRE-positive patient was associated with increased odds of acquiring VRE (odds ratio, 1.64; 95% confidence interval, 1.39–1.92).ConclusionsWe demonstrated that EHR data can be used to quantify the impact of HCW-mediated patient connections on transmission of VRE in the hospital. Defining incident acquisition risk of multidrug-resistant organisms through HCWs connections from EHR data in real-time may aid implementation and evaluation of interventions to contain their spread.

Interplay Between Patient Colonization and Environmental Contamination With Vancomycin-Resistant Enterococci and Their Association With Patient Health Outcomes in Postacute Care.

BackgroundThe clinical utility of patient and environmental surveillance screening for vancomycin-resistant enterococci (VRE) in the postacute care setting has not been definitively clarified. We assessed the longitudinal relationship between patient colonization and room contamination, and we established their association with unfavorable health outcomes.MethodsFour hundred sixty-three postacute care patients were followed longitudinally from enrollment to discharge for up to 6 months. Multiple body and environmental sites were sampled at regular intervals to establish correlation between environmental contamination and patient colonization and with longer than expected stay, unplanned hospitalization, and infections adjusting for sex, age, race, Charlson’s comorbidity index, and physical self-maintenance score.ResultsNew VRE acquisition was more likely in patients residing in contaminated rooms (multivariable odds ratio [OR] = 3.75; 95% confidence interval [CI], 1.98–7.11) and vice versa (OR = 3.99; 95% CI, 2.16–7.51). New acquisition and new contamination were associated with increased length of stay (OR = 4.36, 95% CI = 1.86–10.2 and OR = 4.61, 95% CI = 1.92–11.0, respectively) and hospitalization (OR = 2.42, 95% CI = 1.39–4.22 and OR = 2.80, 95% CI = 1.52–5.12). New-onset infections were more common with higher VRE burdens (15% in the absence of VRE, 20% when after VRE isolation only on the patient or only in the room, and 29% after VRE isolation in both the patient and the room).ConclusionsRoom contamination with VRE is a risk factor for patient colonization, and both are associated with future adverse health outcomes in our postacute care patients. Further research is warranted to establish whether VRE screening may contribute to better understanding of risk assessment and adverse outcome prevention in postacute care.

Risk factors for vancomycin-resistant enterococcus acquisition during a large outbreak in patients aged 65\u2009years and older

BackgroundIn the context of an aging population, identifying risk factors for Vancomycin-resistant enterococci (VRE), specific to older people, is important. However, if age is a known risk factor for VRE infection, a limited number of studies have focused on older patients. This study aimed to identify potential risk factors for VRE acquisition in a population aged 65 years and older, during a large VRE outbreak that occurred in a teaching hospital in Lyon, France, from December 2013 to July 2014.MethodsThe present retrospective, multi-center, descriptive, and analytical study used part of a previous cohort, and included only a sub-group of patients aged 65 years and older. The analysis of the factors included in the original study was completed with factors more specific to geriatric patients. Inclusion criteria were patients aged 65 years and older, in contact with a VRE index patient. Patients were screened by rectal swabs. Univariate and multivariate logistic regression analyses were performed.ResultsA total of 180 VRE contacts were included and 18 patients became carriers. Multivariate analysis showed that risk factors for VRE acquisition in older people included major contact type (RR: 5.31, 95%CI [1.33; 21.19]), number of antibiotics used (RR: 1.36, 95%CI [1.04; 1.76]), a score of McCabe = 2 (RR: 116.39, 95%CI [5.52; 2455.98]), ethylism (RR: 5.50, 95%CI [1.49; 20.25]), and dementia (RR: 7.50, 95%CI [1.89; 29.80]).ConclusionsThis study was able to demonstrate risk factors for VRE acquisition in older people. These risk factors should be taken into account when in the presence of older people in a VRE infected unit.

Potential impact of removing metronidazole from treatment armamentarium of mild acute Clostridioides difficile infection.

Aim: Recent guidelines recommended removing metronidazole as a therapeutic option for Clostridioides difficile infections (CDI). However, superiority of vancomycin over metronidazole in mild CDI is not established and use of vancomycin might lead to emergence of vancomycin-resistant enterococci (VRE). Patients & methods: A retrospective cohort study and efficacy analyses were conducted at Shamir Medical Center, Israel (2010-2015), among adults with acute CDI. Results:A total of409 patients were enrolled. In multivariable analyses, metronidazole was noninferior to vancomycin for mild CDI, but vancomycin was an independent predictor for post-CDI VRE acquisition. Conclusion: A significant independent association was evident between treatment with vancomycin and, later, acquisition of VRE. In first episodes of mild acute CDI, metronidazole should be considered a valid therapeutic option.

2846. Perirectal Samples for Analysis of the Gut Microbiota as a Predictive Tool for Multi-drug-Resistant Organism (MDRO) Acquisition in Nursing Facility (NF) Patients

BackgroundMost research examining the association between gut microbiota disruption and MDRO acquisition has been done in acute care settings. Obtaining stool samples in older NF adults is challenging. We hypothesized that perirectal samples can be used as a proxy of the gut microbiota. This prospective cohort study investigated the association between perirectal swab-derived gut microbiota features in newly admitted NF patients and the acquisition of vancomycin-resistant Enterococcus and/or resistant Gram-negative bacteria (rGNB) within 14 days.MethodsPatients were recruited at 6 MI NFs from September 2016 to October 2018 as part of a larger NIH-funded trial. Colonization status was determined by culture swabs collected from multiple body sites at enrollment, d7, and d14. Our analysis focused on patients with no MDRO at baseline, a perirectal swab collected at baseline, and at least one follow-up visit. The V4 region of the 16S rRNA gene was sequenced from samples and processed with the mothur bioinformatics pipeline. Sequences typically associated with the skin microbiota were removed. The primary outcome was any MDRO acquisition. Exposures of interest included patient and microbiota characteristics. The Microbiome Health Index (MHI) was used to assess microbiota health. An MHI of 0 indicates a balanced abundance between taxa associated with protection and dysbiosis; an MHI above/below 0 suggests better/poorer health, respectively (Figure 1).ResultsAmong 60 eligible patients (Table 1), 18 (30%) acquired MDROs within 14 days of enrollment (3 VRE, 13 rGNB, 2 both). The baseline microbiota features differed significantly in those who acquired a new MDRO. Of the major 8 phyla found across samples, patients who acquired an MDRO were depleted in the number of phyla present (4.4 ± 1.1 vs. 5 ± 1.1; P = 0.08) (Figure 2). The log-transformed relative abundance of Enterococcus was enriched in patients who acquired an MDRO (−0.7 ± 3.41) compared with those who did not (−4.2 ± 4.8; P < 0.01) (Figure 3). An MHI below 0 was predictive of MDRO acquisition after adjusting for catheter use within 30 days before baseline (adjusted OR 4.9; 95% CI 1.1–21.1).ConclusionMicrobiota metrics calculated from perirectal samples are predictive of MDRO acquisition. The clinical utility of perirectal samples warrants further assessment. Disclosures All Authors: No reported Disclosures.

577. The Role of Healthcare Worker-Mediated Contact Networks in the Transmission of Vancomycin-Resistant Enterococci

BackgroundHealthcare workers (HCWs) commonly contact multiple patients daily and serve as an important vector for transmission of pathogens such as vancomycin-resistant enterococci (VRE). Characterizing the HCW-patient network is difficult, which limits understanding of the role of HCWs in the horizontal transmission of pathogens. Electronic health records (EHR) present an opportunity to generate HCW-mediated contact networks and evaluate their impact on transmission.MethodsRetrospective analysis of patients (PT) admitted to a medical intensive care unit and solid-organ transplant unit between July 2016 and June 2017. Clinical and demographic information, including VRE surveillance swab outcomes, were extracted from the hospital EHR system. PT-HCW-PT connections were defined as HCW contacts with a patient within an hour of another patient. Multi-variable logistic regression was used to analyze factors associated with unit-acquired VRE colonization incidence.ResultsA total of 2,336 patients had a recorded interaction with 4,956 unique HCWs. 146 patients were colonized with VRE on unit-admission, and 29 patients had unit-acquired VRE colonization. HCWs had contact with ~2 (range: 1–23) patients a day and ~6 (range: 1–58) contacts with patients per day (Figure 1), though rates varied by HCW-type. Patients were contacted by ~7 different HCWs resulting in ~28 contacts per day, with nurses being the most common (Figure 2). This resulted in approximately 10 PT-HCW-PT connections per day (range: 1–33) to an average of 3 other patients. After adjusting for known VRE acquisition risk factors, HCW connections to other patients with VRE significantly increased the risk of VRE acquisition (odds ratio = 1.32; 95% CI: 1.20–1.44; Table 1).ConclusionUnderstanding how HCWs connect patients can elucidate how pathogens, such as VRE, spread in the hospital. We demonstrated how EHR data can inform how HCWs connect patients to spread HAIs and the impact of those connections on the spread of VRE. Though EHR data have limitations, as certain activities and contacts are not logged into the system, they provide a scalable and generalizable source for understanding how patients are connected and can be utilized to reduce the spread of nosocomial infections. Disclosures All authors: No reported disclosures.

2457. Data Science for Outbreak Investigation: Identifying Risk Factors, Tracing Contacts, and Eliciting Transmission Pathways in a Vancomycin-Resistant Enterococci (VRE) Outbreak

BackgroundIn 2018 we experienced a nosocomial outbreak due to vancomycin-resistant enterococci (VRE) in our hospital network. Our goals were to characterize risk factors for VRE acquisition, elicit potential hot spots of transmission, and delineate an optimized approach to tracing contacts.MethodsWe assembled diverse datasets of variable quality and covering different aspects of care from electronic medical records generated during the outbreak period (1/2018–9/2018). Patients who tested VRE-positive during this period were compared with controls with up to 3 negative screenings. First, we identified risk factors for VRE colonization by means of uni- and multivariate analyses. Next, we elicited transmission pathways by detecting commonalities between VRE cases, and determined whether patients with characteristics and connections similar to VRE cases were missed by our current contact tracing strategy.ResultsWe compared 221 VRE patients to 33,624 controls. Independent predictors of VRE colonization were ICU admission (OR 4.9, with 95% confidence interval [3.7–6.5], P < 0.001)], number of records in the database (a proxy for severity-of-illness, OR 1.1 [1.1–1.1], P < 0.001), length of hospital stay (OR 2.7 [2.0–3.5], P < 0.001), age (OR 1.3 [1.2–1.4], P < 0.001), and weeks of antibiotics (OR 1.2 [1.1–1.3], P < 0.001). By using complex network analysis, we were able to establish three main pathways by which the 221 VRE cases are connected: healthcare personnel, medical devices, and patient rooms. This multi-dimensional network extends beyond our current contact tracing strategy, which captures inpatients based on geographical proximity (cf. figure).ConclusionIn this outbreak investigation based on a large electronic healthcare data collection, we found three main risk factors for being a VRE carrier (ICU admission, length of hospital stay, antibiotic exposure), along with three important links between VRE cases (healthcare personnel, medical devices, patient rooms). Data science is likely to provide a better understanding of outbreaks, but interpretations should take data maturity, the scope of included sources, and potential confounding factors into account. Disclosures All authors: No reported disclosures.

Sample Size Estimates for Cluster-Randomized Trials in Hospital Infection Control and Antimicrobial Stewardship

An important step in designing, executing, and evaluating cluster-randomized trials (CRTs) is understanding the correlation and thus nonindependence that exists among individuals in a cluster. In hospital epidemiology, there is a shortage of CRTs that have published their intraclass correlation coefficient or coefficient of variation (CV), making prospective sample size calculations difficult for investigators. To estimate the number of hospitals needed to power parallel CRTs of interventions to reduce health care-associated infection outcomes and to demonstrate how different parameters such as CV and expected effect size are associated with the sample size estimates in practice. This longitudinal cohort study estimated parameters for sample size calculations using national rates developed by the Centers for Disease Control and Prevention for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, central-line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and Clostridium difficile infections (CDI) from 2016. For MRSA and vancomycin-resistant enterococci (VRE) acquisition, outcomes were estimated using data from 2012 from the Benefits of Universal Glove and Gown study. Data were collected from June 2017 through September 2018 and analyzed from September 2018 through January 2019. Calculated number of clusters needed for adequate power to detect an intervention effect using a 2-group parallel CRT. To study an intervention with a 30% decrease in daily rates, 73 total clusters were needed (37 in the intervention group and 36 in the control group) for MRSA bacteremia, 82 for CAUTI, 60 for CLABSI, and 31 for CDI. If a 10% decrease in rates was expected, 768 clusters were needed for MRSA bacteremia, 875 for CAUTI, 631 for CLABSI, and 329 for CDI. For MRSA or VRE acquisition, 50 or 40 total clusters, respectively, were required to observe a 30% decrease, whereas 540 or 426 clusters, respectively, were required to detect a 10% decrease. This study suggests that large sample sizes are needed to appropriately power parallel CRTs targeting infection prevention outcomes. Sample sizes are most associated with expected effect size and CV of hospital rates.

A retrospective cohort study of antibiotic exposure and vancomycin-resistant Enterococcus recolonization.

In the National Institutes of Health (NIH) Clinical Center, patients colonized or infected with vancomycin-resistant Enterococcus (VRE) are placed in contact isolation until they are deemed "decolonized," defined as having 3 consecutive perirectal swabs negative for VRE. Some decolonized patients later develop recurrent growth of VRE from surveillance or clinical cultures (ie, "recolonized"), although that finding may represent recrudescence or new acquisition of VRE. We describe the dynamics of VRE colonization and infection and their relationship to receipt of antibiotics. In this retrospective cohort study of patients at the National Institutes of Health Clinical Center, baseline characteristics were collected via chart review. Antibiotic exposure and hospital days were calculated as proportions of VRE decolonized days. Using survival analysis, we assessed the relationship between antibiotic exposure and time to VRE recolonization in a subcohort analysis of 72 decolonized patients. In total, 350 patients were either colonized or infected with VRE. Among polymerase chain reaction (PCR)-positive, culture (Cx)-negative (PCR+/Cx-) patients, PCR had a 39% positive predictive value for colonization. Colonization with VRE was significantly associated with VRE infection. Among 72 patients who met decolonization criteria, 21 (29%) subsequently became recolonized. VRE recolonization was 4.3 (P = .001) and 2.0 (P = .22) times higher in patients with proportions of antibiotic days and antianaerobic antibiotic days above the median, respectively. Colonization is associated with clinical VRE infection and increased mortality. Despite negative perirectal cultures, re-exposure to antibiotics increases the risk of VRE recolonization.

A trial of pulsed xenon ultraviolet disinfection to reduce Clostridioides difficile infection

An intervention was designed to test whether the addition of an ultraviolet (UV) disinfection step after terminal cleaning would be helpful in reducing Clostridium difficile infection (CDI) rates in a real-world situation. This study was a quasi-experimental design using 3 units as intervention units for the intervention and 3 similar units as control units. Intervention units 2 hematology and bone marrow transplant units and one medical-surgical unit at a large teaching hospital in the Midwest. UV disinfection was added after patient discharge and terminal cleaning in the intervention units. At baseline, CDI rates in the intervention and control arms were similar. During the 6 months of UV disinfection, the CDI rate in the intervention units decreased to 11.2 per 10,000 patient days, compared with 28.7 per 10,000 patient days in the control units (P = .03). In addition, the intervention units also saw a reduction in vancomycin-resistant enterococci acquisition. The addition of UV disinfection to the terminal cleaning resulted in a reduction in CDI that has been sustained over several months 2 years.

Mathematical modelling of vancomycin-resistant enterococci transmission during passive surveillance and active surveillance with contact isolation highlights the need to identify and address the source of acquisition

BackgroundClinical studies and mathematical simulation suggest that active surveillance with contact isolation is associated with reduced vancomycin-resistant enterococci (VRE) prevalence compared to passive surveillance. Models using pre- and post-intervention data that account for the imperfect observation and serial dependence of VRE transmission events can better estimate the effectiveness of active surveillance and subsequent contact isolation; however, such analyses have not been performed.MethodsA mathematical model was fitted to surveillance data collected pre- and post-implementation of active surveillance with contact isolation in the haematology-oncology ward. We developed a Hidden Markov Model to describe undetected and observed VRE colonisation/infection status based on the detection activities in the ward. Bayesian inference was used to estimate transmission rates. The effectiveness of active surveillance was assumed to be via increased detection and subsequent contact isolation of VRE positive patients.ResultsWe estimated that 31% (95% credible interval: 0.33–85%) of the VRE transmissions were due to cross-transmission between patients. The ratio of transmission rates from patients with contact isolation versus those without contact isolation was 0.33 (95% credible interval: 0.050–1.22).ConclusionsThe majority of the VRE acquisitions in the haematology-oncology ward was estimated to be due to background rates of VRE, rather than within ward patient to patient acquisition. The credible interval for cross-transmission was wide which results in a large degree of uncertainty in the estimates. Factors that could account for background VRE acquisition include endogenous acquisition from antibiotic selection pressure and VRE in the environment. Contact isolation was not significantly associated with reduced VRE transmission in settings where the majority of VRE acquisition was due to background acquisition, emphasising the need to identify and address the source of acquisition. As the credible interval for the ratio of VRE transmission in contact isolated versus non-contact isolated patients crossed 1, there is a probability that the transmission rate in contact isolation was not lower. Our finding highlights the need to optimise infection control measures other than active surveillance for VRE and subsequent contact isolation to reduce VRE transmission. Such measures could include antimicrobial stewardship, environmental cleaning, and hand hygiene.

Effectiveness of ultraviolet disinfection in reducing hospital-acquired Clostridium difficile and vancomycin-resistant Enterococcus on a bone marrow transplant unit.

To determine the effectiveness of ultraviolet (UV) environmental disinfection system on rates of hospital-acquired vancomycin-resistant enterococcus (VRE) and Clostridium difficile. Using active surveillance and an interrupted time-series design, hospital-acquired acquisition of VRE and C. difficile on a bone marrow transplant (BMT) unit were examined before and after implementation of terminal disinfection with UV on all rooms regardless of isolation status of patients. The main outcomes were hospital-based acquisition measured through (1) active surveillance: admission, weekly, and discharge screening for VRE and toxigenic C. difficile (TCD) and (2) clinical surveillance: incidence of VRE and CDI on the unit. Bone marrow transplant unit at a tertiary-care cancer center.ParticipantsStem cell transplant (SCT) recipients.InterventionTerminal disinfection of all rooms with UV regardless of isolation status of patients. During the 20-month study period, 579 patients had 704 admissions to the BMT unit, and 2,160 surveillance tests were performed. No change in level or trend in the incidence of VRE (trend incidence rate ratio [IRR], 0.96; 95% confidence interval [CI], 0.81-1.14; level IRR, 1.34; 95% CI, 0.37-1.18) or C. difficile (trend IRR, 1.08; 95% CI, 0.89-1.31; level IRR, 0.51; 95% CI, 0.13-2.11) was observed after the intervention. Utilization of UV disinfection to supplement routine terminal cleaning of rooms was not effective in reducing hospital-acquired VRE and C. difficile among SCT recipients.

Patient contact is the main risk factor for vancomycin-resistant Enterococcus contamination of healthcare workers' gloves and gowns in the intensive care unit.

To determine which healthcare worker (HCW) roles and patient care activities are associated with acquisition of vancomycin-resistant Enterococcus (VRE) on HCW gloves or gowns after patient care, as a surrogate for transmission to other patients. Prospective cohort study. Medical and surgical intensive care units at a tertiary-care academic institution.ParticipantsVRE-colonized patients on Contact Precautions and their HCWs. Overall, 94 VRE-colonized patients and 469 HCW-patient interactions were observed. Research staff recorded patient care activities and cultured HCW gloves and gowns for VRE before doffing and exiting patient room. VRE were isolated from 71 of 469 HCWs' gloves or gowns (15%) following patient care. Occupational/physical therapists, patient care technicians, nurses, and physicians were more likely than environmental services workers and other HCWs to have contaminated gloves or gowns. Compared to touching the environment alone, the odds ratio (OR) for VRE contamination associated with touching both the patient (or objects in the immediate vicinity of the patient) and environment was 2.78 (95% confidence interval [CI], 0.99-0.77) and the OR associated with touching only the patient (or objects in the immediate vicinity) was 3.65 (95% CI, 1.17-11.41). Independent risk factors for transmission of VRE to HCWs were touching the patient's skin (OR, 2.18; 95% CI, 1.15-4.13) and transferring the patient into or out of bed (OR, 2.66; 95% CI, 1.15-6.43). Patient contact is a major risk factor for HCW contamination and subsequent transmission. Interventions should prioritize contact precautions and hand hygiene for HCWs whose activities involve touching the patient.