VRE Colonization Research Articles

Use of Whole Genome Sequencing for Investigation of Potential Hospital-Acquired Vancomycin Resistant Enterococcus

Background: Whole genome sequencing (WGS) is a relatively new method for analyzing outbreaks and modes of transmission, particularly for multidrug resistant bacteria. This study sought to investigate clusters of patients with genetically related Vancomycin-Resistant Enterococcus spp. (VRE) bacteremia for shared hospital environmental exposures. Methods: All VRE blood culture isolates from patients from July 1, 2021 to June 30, 2022 underwent Illumina WGS. Core single nucleotide polymorphisms (SNPs) were identified, and multi-locus sequence typing (MLST) was performed across the VRE isolates. Clusters were defined as isolates with 15 or fewer core genome SNPs and were investigated for potential transmission routes. For each cluster, patients were evaluated in the 12 weeks before and after the first VRE isolate for shared hospital environmental exposures (hospital unit, patient rooms, procedural rooms, and radiology suites). Hospital units were comprised of patient rooms located geographically together on the same floor of the hospital. Results: A total of 82 VRE isolates underwent WGS. Thirty-eight (46%) clustered genetically with at least one other isolate. Clusters included 2 to 15 patients per group and represented 10 distinct MLST subgroups (Figure 1). Nine hundred and thirty-nine hospital environmental exposures were identified across the 38 patients. For each cluster, there was a total of 341 (36.3%) shared exposures. Shared environmental exposures occurred in radiology suites (35, 38.5%), patient rooms (32, 35.6%) and procedural rooms (23, 25.6%). Of the patients who shared the same hospital unit, 10 (31.3%) had the same patient room with 7 (70%) of them being in the emergency department (ED). Overall, the ED represented 7 (21.9%) of the shared hospital units. Each cluster had at least one shared hospital environmental exposure found. Conclusions: Use of WGS can help investigate outbreak clusters of resistant organisms such as VRE. In this study, nearly half of all VRE blood isolates were able to be segregated into clusters with at least one other isolate. Although VRE colonization of hospital rooms is well described, patient rooms represented the smallest proportion of shared hospital environmental exposures. This study thus suggests other environmental transmission routes such as radiology suites and procedural rooms warrant closer investigation.

Vancomycin resistant enterococcus risk factors for hospital colonization in hematological patients: a matched case-control study

BackgroundVancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group.MethodsA retrospective, single center, case–control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (≥ 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization.ResultsA total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively).ConclusionsAntimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.

Cessation of Rectal Screening for Vancomycin-Resistant Enterococci: Experience from a Tertiary Care Hospital from Türkiye.

Here, we compared the impact of different polices on the epidemiology of Vancomycin-resistant Enterococcus faecium bloodstream infections (VRE-BSIs) in a tertiary care hospital including two hospital buildings (oncology and adult hospitals) in the same campus. All patients who were hospitalized in high-risk units were screened weekly for VRE colonization via rectal swab between January 2006 and January 2013. After January 2013, VRE screening was only performed in cases of suspicion of VRE outbreak and during point prevalence studies to evaluate the epidemiology of VRE colonization. Contact precautions were in place for all VRE-positive patients. The incidence density rates of hospital-acquired (HA)-VRE-BSIs were compared between two periods. While the rate of VRE colonization was higher in the second period (5% vs. 9.5% (p < 0.01) for the adult hospital, and 6.4% vs. 12% (p = 0.02 for the oncology hospital), there was no increase in the incidence rate HA-VRE BSIs after the cessation of routine rectal screening in either of the hospitals. Screening policies should be dynamic and individualized according to the epidemiology of VRE as well as the workforce and cost. Periodical rectal screening of VRE can be discontinued if suspicion of an outbreak can be carefully monitored.

Risk factors for gut colonization with vancomycin-resistant enterococci among Bulgarian critically ill patients

Vancomycin-resistant enterococci (VRЕ) are recognized as important hospital pathogens which have become common in patients admitted to the intensive care units (ICUs). The purpose of this study was to evaluate the incidence of and the risk factors for colonization with VRE among ICU patients. A total of 91 patients who had duration of hospitalization more than 48 h and without infection caused by VRE or/and other microorganisms in the ICU at University Hospital, Pleven were screened for colonization with VRE. The following data were collected: demographic characteristics, clinical information and antimicrobials use. The statistical analysis was performed using SPSS version 27.0. Colonization with VRE was established in 22 patients and one was carrying two enterococcal species. A total of 23 VRE were isolated. The univariate analysis showed that the postoperative critical cares (p < 0.001), cardiovascular diseases (p = 0.009) and the presence of an endotracheal tube (p = 0.003) were risk factors for colonization with VRE. Also, the postoperative critical cares (p = 0.021) and cardiovascular diseases (p = 0.018) were confirmed as independent risk factor for VRE acquisition by multivariate analysis. The prevalence of VRE colonization among the ICU patients was relatively high (24.2%). Risk factors for acquisition of intestinal VRE were the postoperative cares, cardiovascular diseases and the presence of an endotracheal tube.

Development of a workflow for the detection of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis from rectal swabs using the spectra VRE medium

BackgroundSpectra™ VRE agar (Remel, Lenexa, KS) is a chromogenic agar that is FDA approved for screening patients for VRE colonization. The package insert recommends confirming isolates with identification and susceptibility testing, but confirming every culture delays time to result. Given the agar’s historic high specificity for E. faecium isolates, we theorized the agar could be utilized as a stand-alone screening to minimize reagents and time.AimOur laboratory sought to develop a workflow to optimize the use of the medium.MethodsWe plated 3,815 rectal swabs to the Spectra VRE agar and compared results to traditional identification and susceptibility testing.ResultsDark blue or purple colonies on the agar demonstrated a sensitivity of 98% and specificity of 85% for detection of VRE faecium, but light blue colonies were significantly less specific for E. faecalis.ConclusionsWe streamlined our workflow to accept dark blue or purple colonies as VRE faecium and plan to perform additional testing only on light blue colonies. Interestingly, higher quantity of growth increased the accuracy of the agar. In the future, growth quantity may be used to further streamline the workflow once more data is obtained.

2035. Detecting Vancomycin-resistant Enterococci infection in an immunosuppressed population after screening

Abstract Background Vancomycin-Resistant Enterococci (VRE) are major pathogens for severely immunosuppressed patients. Because VRE are common pathogens in our institution, such patients are often empirically treated to cover VRE, exposing them to broad-spectrum antimicrobials. Analogous to nasal screening for Methicillin-resistant Staphylococcus aureus carriage, targeted VRE surveillance is performed to identify and isolate colonized patients to reduce transmission. To assess risks and benefits of empiric therapy, we evaluated this surveillance procedure. Methods All patients admitted to two inpatient hospital units from 01/01/2019 to 12/31/2021 had routine perirectal VRE surveillance ordered and results retrospectively reviewed. One swab from each Culturette set was tested by vanA PCR, and the other was inoculated on CHROMEID® VRE (Biomerieux) if the PCR was positive. Subsequent clinical cultures of any site within 14 days of surveillance screening were reviewed for VRE. Results 1133 patients were screened; 46 (4.1%) patients had VRE colonization. Within 2 weeks following VRE screening 20 patients had clinical samples that were positive for an Enterococcus species (14 in the first 7 days and 6 in days 8-14). The most common sites of clinical cultures were urine, 8 (40%), wound, 4 (20%), intra-abdominal, 4 (20%), and blood, 2 (10%). No clinical culture sample contained VRE. Conclusion The rate of VRE carriage was low in this population, raising the question of the value of broad-spectrum empiric therapy coverage for VRE. No VRE infections were subsequently detected in any patients irrespective of surveillance. The negative predictive value for clinical VRE infection was 100% with negative surveillance screening in this population. Disclosures All Authors: No reported disclosures.

Predictors of Vancomycin-Resistant Enterococcus spp. Intestinal Carriage among High-Risk Patients in University Hospitals in Serbia.

The predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3–7, 8–15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed.

Development and Validation of a Tool for the Prediction of Vancomycin-Resistant Enterococci Colonization Persistence-the PREVENT Score.

ABSTRACTVancomycin-resistant enterococci (VRE) are nosocomial pathogens with increasing prevalence worldwide. Extensive hygiene measures have been established to prevent infection transmission in hospitals. Here, we developed a predictive score system (the predictive vancomycin-resistant enterococci [PREVENT] score) to identify the clearance or persistence in patients with a history of VRE carrier status at readmission. Over a cumulative 3-year period, patients with a positive VRE carrier status were included. The study population was recruited in two successive time periods and separated into training data for predictive score development and validation data for evaluation of the predictive power. The risk factors for persistent VRE colonization were analyzed in a univariable analysis before development of a logistic regression model based on the potential risk factors. The score points were determined proportionally to the beta coefficients of the logistic regression model. The data from 448 (79%) patients were used as the training data, and those from 119 (21%) as the validation data. Multivariable analysis revealed the following variables as independent risk factors: age of ≥60 years, hemato-oncological disease, cumulative antibiotic treatment for >4 weeks, and a VRE infection. The resulting logistic regression model exhibited an acceptable area under the curve (AUC) of 0.81 (95% confidence interval [CI], 0.72 to 0.91). The predictive score system had a sensitivity of 82% (95% CI, 65 to 93%) and a specificity of 77% (95% CI, 66 to 85%). The developed predictive score system is a useful tool to assess the VRE carrier status of patients with a history of VRE colonization. On the basis of this risk assessment, more focused and cost-effective infection control measures can be implemented.IMPORTANCE Given the increasing relevance of VRE as nosocomial pathogens worldwide, infection prevention and control measures, including patient isolation and contact precautions, are indispensable to avoid their spread in the hospital setting. In this study, we developed and validated the PREVENT score, a tool for rapid risk assessment of VRE persistence in patients with a history of previous VRE colonization. The score is designed to be easily performed, employing clinical information available in a regular admission setting and immediately providing information to inform the decision of whether to adopt patient isolation and contact precautions during the hospital stay. After validation, the score was shown to accurately identify patients with persistent VRE colonization upon admission, representing a suitable option as (i) a complementary method yielding preliminary results significantly more quickly than culture-based VRE detection techniques and (ii) an alternative strategy for VRE detection in settings in which microbiological VRE screening is not routinely performed due to limited resources.

Characterization of enterococcal urinary tract infections, with special reference to High Level Aminoglycoside Resistance (HLGR)

Background: Multidrug-resistant Enterococci are major problem and are increasingly reported worldwide. Enterococci have converted over the years from a normal gut commensal to opportunistic nosocomial as well as community acquired pathogen. High level resistance to Aminoglycosides and concomitant resistance to Vancomycin reduces the treatment options and complicated the management of serious infections caused by Enterococci. Methods and materials: A retrospective analysis was conducted in the Department of Microbiology, SGPGI for a period of 10 months from Jan 2018 to October 2018. Enterococcus isolated from urine colony counts of ≥10 5 colony-forming units per ml (CFU/ml) were included in the study. Identification was performed by MALDI TOF and Antimicrobial susceptibility testing was performed by the VITEK 2.0 in accordance to CLSI guidelines. Results: In the study, 186 Enterococci spp. were isolated out of which 159/186 (85.48%) were E.faecalis and 27/186 (14.51%) were E.faecium. High Level Aminoglycoside resistance (HLG) was seen in 67/186 (36.02%) of which E.faecalis comprised of 43/67 (64.17%). Three isolates, all identified as E. faecium, were found to be resistant to High level Gentamycin and Vancomycin. Overall, antibiogram of the isolates showed a high resistance to ampicillin, followed by ciprofloxacin, High level Gentamycin (36.02%), High level Streptomycin (36.02%), vancomycin (1.61%), teicoplanin (1.61%), linezolid (1.61%) and nitrofurantoin (1%). A subset of E.faecalis were randomly selected and characterised for HLG resistance genes. DISCUSSION-History of recent hospitalization and the presence of indwelling urinary catheter was associated with VRE and HLGR enterococci infection or colonization. Overall, High-Level Aminoglycoside Resistance (HLAR) was observed more than glycopeptide resistance. Isolates resistant to HLG but susceptible to vancomycin expressed more virulence factors. Conclusion: This study highlights the temporal increase in antimicrobial resistance and in MDR bacteria causing UTI creates important therapeutic limitations. Surveillance strategies need to be upgraded and implemented in order to prevent the emergence and further spread of not only VRE but also HLAR enterococci in the hospital.

Predicting Vancomycin-Resistant Enterococci (VRE) and Carbapenem-Resistant Organism (CRO) Colonization in the Intensive Care Unit

Background: Rapidly identifying patients colonized with multidrug-resistant organisms (MDROs) upon ICU admission is critical to control and prevent the spread of these pathogens in healthcare facilities. Electronic health records (EHR) provide a rich source of data to predict the likelihood of MDRO colonization at admission, whereas surveillance methods are resource intensive and results are not immediately available. Our objectives were (1) to predict VRE and CRO colonization at ICU admission and (2) to identify patient subpopulations at higher risk for colonization with these MDROs. Methods: We conducted a retrospective analysis of patients aged ≥16 years admitted to any of 6 medical or surgical intensive care units (ICU) in the Johns Hopkins Hospital from July 1, 2016, through June 30, 2018. Perirectal swabs were collected at ICU unit admission and were tested for VRE and CRO. Patient demographic data, prior hospitalizations, and preadmission clinical data, including prior medication administration, prior diagnoses, and prior procedures, were extracted to develop prediction models. We employed the machine-learning algorithms logistic regression (LR), random forest (RF), and XGBoost (XG). The sum of sensitivity and specificity (ie, Youden’s index) was selected as the performance metric. Results: In total, 5,033 separate ICU visits from 3,385 patients were included, where 555 (11%) and 373 (7%) admissions tested positive for VRE and CRO, respectively. The sensitivity and specificity of our models for VRE were 78% and 80% with LR, 80% and 82% with RF, and 77% and 87% with XG. Predictions for CRO were not as precise, with LR at 73% and 53%, RF at 81% and 48%, and XG at 69% and 61%. The XG algorithm was the best-performing algorithm for both VRE and CRO. Prior VRE colonization, recent (&lt;180 days) long-term care facility stay, and prior hospitalization &gt;60 days were the key predictors for VRE, whereas the primary predictor for CRO colonization was prior carbapenem use. Conclusions: We demonstrated that EHR data can be used to predict &gt;75% of VRE positive cases with a &lt;15% false-positive rate and ~70% of CRO cases with a &lt;40% false-positive rate. Future studies using larger sample sizes may improve the prediction accuracy and inform model generalizability across sites and thus reduce the risk of transmission of MDROs by rapidly identifying MDRO-colonized patients.Funding: This work was funded by the Centers for Disease Control and Prevention (CDC) Epicenters Program (Grant Number 1U54CK000447) and the CDC MInD-Healthcare Program (Grant Number 1U01CK000536).Disclosures: Aaron Milstone, BD (consulting)

Oral vancomycin prophylaxis against recurrent Clostridioides difficile infection: Efficacy and side effects in two hospitals.

The data regarding the effectiveness of chemical prophylaxis against recurrent C. difficile infection (CDI) remain conflicting. Retrospective cohort study on the effectiveness of oral vancomycin for prevention of recurrent CDI. Two academic centers in New York. Two participating hospitals implemented an automated alert recommending oral vancomycin 125 mg twice daily in patients with CDI history scheduled to receive systemic antimicrobials. Measured outcomes included breakthrough and recurrent CDI rates, defined as CDI during and 1 month after initiation of prophylaxis, respectively. A self-controlled, before-and-after study design was employed to examine the effect of vancomycin prophylaxis on the prevalence of vancomycin-resistant Enterococcus spp (VRE) colonization and infection. We included 264 patients in the analysis. Breakthrough CDI was identified in 17 patients (6.4%; 95% confidence interval [CI], 3.8%-10.1%) and recurrent in 22 patients (8.3%; 95% CI, 5.3%-12.3%). Among the 102 patients with a history of CDI within the 3 months preceding prophylaxis, 4 patients (3.9%; 95% CIs, 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.8%; 95% CIs, 4.1%-16.1%). In the 3-month period following vancomycin prophylaxis, we detected a statistically significant increase in both the absolute number of VRE (χ2, 0.003) and the ratio of VRE to VSE isolates (χ2, 0.003) compared to the combined period of 1.5 months preceding and the 3-4.5 months following prophylaxis. This effect persisted 6 months following prophylaxis. Prophylactic vancomycin is an effective strategy to prevent CDI recurrence, but it increases the risk of VRE colonization. Thus, a careful selection of patients with high benefit-to-risk ratio is needed for the implementation of this preventive policy.

Prospective infection surveillance and systematic screening for vancomycin-resistant enterococci in hematologic and oncologic patients – findings of a German tertiary care center

IntroductionVancomycin-resistant enterococci (VRE) are emerging multidrug-resistant bacteria. They can cause serious nosocomial infections, especially in immunocompromised patients. Objectives and methodsIn this study, we aimed to determine the burden of intestinal VRE colonization and clinically relevant infection in adult hematologic and oncologic patients at a tertiary care clinic in Germany based on prospective infection surveillance and an active screening program. ResultsIn a 12 month period, 132 of 555 patients had intestinal VRE-colonization (23.8%) and four patients (0.7% of the entire cohort, and 3.0% of those colonized with VRE) developed a nosocomial infection with VRE. ConclusionsThe prospective surveillance and active screening for VRE was very useful to determine the true ratio of intestinal colonization to infection and thus helps to shape infection control management.

Rapid identification of the vanA/vanB resistance determinant in Enterococcus sp. from blood cultures using the Cepheid Xpert vanA/vanB cartridge system

Especially in immunocompromised and intensive care patients VRE sepsis is associated with high mortality. The GeneXpert vanA/vanB assay is marketed for fast molecular surveillance of VRE colonization in peri-anal and rectal swabs. The aim of this study was to evaluate this assay for its usefulness for rapid identification of the vanAB determinant from positive blood cultures. During an evaluation phase, 33/34 blood cultures (negative = 13; vanA = 1; and vanB = 19) were correctly identified. In the validation phase 205/211 blood cultures were correctly identified (negative, n = 160; vanA, n = 2; vanB, n = 43). Sensitivity and specificity calculated from valid tests was 100% (95% CI: 90.2–100%) and 100% (95% CI: 97.1–100%), respectively. The error rate was 2.8%. The Xpert vanA/vanB cartridge is a reliable tool in the rapid molecular identification of the vanA and vanB determinant from positive blood cultures with moderate inhibition rates (2.8%) and high PPV and NPV. However, additional methods for species identification are required.

Daily Chlorhexidine Gluconate Bathing Reduces the Rate of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Stem Cell Transplantation

Introduction: While hematopoietic stem cell transplantation (HSCT) has great therapeutic potential, intensive conditioning regimens and variability in time to stem cell engraftment result in a period of pancytopenia and immunosuppression in which patients are vulnerable to infection. Bloodstream infections (BSIs) occur in 20-45% of inpatient autologous and allogeneic transplant patients, leading to prolonged hospitalization and increased mortality. One method of infection prevention is daily application of the antiseptic chlorhexidine gluconate (CHG). Daily CHG bathing, either with a CHG wash or with application of CHG-impregnated cloths, has been shown to reduce the incidence of all-cause hospital-acquired BSIs in critically ill patients, such as those in the ICU, though very few studies include HSCT patients. Methods: We conducted an observational cohort study to assess the impact of daily CHG bathing on the rate of BSIs among adults undergoing inpatient HSCT at the Duke University Medical Center. Patients were included if they were admitted for pre-transplant conditioning and inpatient monitoring for allogeneic or autologous HSCT from January 2016 through December 2018. CHG bathing was instituted in January 2017 for all patients admitted to the inpatient HSCT unit using 2% CHG-impregnated cloths (SAGE™), providing one year of data with no CHG bathing and two years of data with bathing. Patients were tracked from admission until unit discharge, transfer, or first infection. Laboratory-confirmed bloodstream infections (LCBI), central-line associated bloodstream infections (CLABSI), and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI) were determined per CDC/NHSN definitions. An additional variable of "clinically-significant infection" was recorded; this included both laboratory-confirmed BSIs and infections deemed significant by the treatment team but that did not meet CDC/NHSN criteria. For example, patients that were febrile, hypotensive, and treated with antibiotics, but with only one positive culture of a common commensal were deemed to have a clinically-significant BSI. Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: High (&gt;75%), Medium (50-75%), Low (1-49%), and None (0%). Baseline characteristics and clinical outcomes between groups were compared via ANOVA, Chi-squared test, or Cochran-Armitage two-sided trend test. Multivariate analysis using the Fine-Grey subdistribution hazard model was conducted to compare time to all infection variables, accounting for the effects of CHG usage, antibiotic prophylaxis regimen, and type of transplant. Results: We evaluated 192 patients hospitalized for HSCT, including 118 (62%) allogeneic transplants and 74 (38%) autologous transplants. Of these, 25 (13%) had high CHG usage, 33 (17%) medium, 45 (23%) low, and 89 (46%) none. Demographics and transplant characteristics were evenly matched between the CHG usage groups with the exception that high usage groups were more likely to receive levofloxacin for antibiotic prophylaxis (p=0.003). Increased CHG usage was significantly associated with decreased incidence of clinically-significant infection (p=0.006), CLABSI (p=0.04), and MBI-LCBI (p=0.002) (Table 1). Multivariate analysis did not demonstrate a significant contribution of antibiotic prophylaxis regimen. No significant difference was found between CHG usage groups in median days to stem cell engraftment, incidence of febrile neutropenia or C. difficile infection, or rashes requiring medical treatment. There were no rashes attributable to CHG usage. Among patients who were VRE rectal swab negative on admission, there was a significant trend toward lower rates of VRE acquisition with increasing CHG usage (High CHG 13.6% vs No CHG 25.3%, p=0.02). Discussion: Increased CHG usage is associated with a significant trend toward lower rates of clinically-significant infection, CLABSI, MBI-LCBI, and VRE colonization in adult inpatients undergoing HSCT. Effects are most strongly seen at &gt;75% daily CHG usage. There were no adverse effects due to CHG application. The significant decrease in MBI-LCBI with topical CHG suggests an interaction between the skin microbial environment and enteric organisms. Therefore, further research exploring the effects of CHG on the skin and gut microbiota is warranted. Disclosures Gasparetto: BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

2414. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in High-Risk Patients

BackgroundStudies suggest oral vancomycin prophylaxis may be effective in preventing Clostridioides difficile infection. These studies are limited by their retrospective design, reliance on local clinical practice patterns, lack of intervention standardization, and limited risk stratification. We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility-onset CDI (HCFO-CDI) in high-risk patients.MethodsWe conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina between October 2018 and April 2019. Admitted high-risk patients (defined as: ≥ 60 years of age, hospitalized ≤ 30 days prior to the index hospitalization and received systemic antibiotics during that prior hospitalization and currently receiving systemic antibiotics) were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days post completion of systemic antibiotics [OVP]), or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), development of VRE colonization after receiving OVP, and adverse effects and cost of OVP.ResultsA total of 100 patients were evaluated, 50 patients in each group. Baseline and hospitalization characteristics were similar in each group. No incidents of HCFO-CDI were diagnosed in the OVP group compared with 6 (12%) in the no prophylaxis group (P = 0.03). CO-HCFA-CDI was not observed in either group. No patients developed new VRE colonization with only 1 patient reporting mild gastrointestinal side-effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $728.25, $60.69 per patient.ConclusionOVP was highly effective in preventing HCFO-CDI. OVP was well tolerated with no apparent risk for VRE colonization. Further prospective investigation is warranted to determine the impact and cost-effectiveness of routine use of OVP in high-risk patients.Disclosures All authors: No reported disclosures.

736. The Use of Bacteriophages to Inhibit Different Strains of Vancomycin-Resistant or Susceptible Enterococci

BackgroundVancomycin-resistant Enterococci (VRE) is a well-known infectious complication among immunocompromised patients, especially hematopoietic cell transplant (HCT) recipients. VRE colonization of the gastrointestinal tract could be associated with VRE bacteremia and worse outcomes in HCT recipients. The use of systemic antibiotics to eradicate VRE colonization is highly discouraged because of the lack of efficacy, the rapid onset of antibiotic resistance, and the disruption of the normal microbiota. Bacteriophages (phages) may constitute a good alternative to antibiotics to eliminate specific pathogens without disrupting the patient’s normal microbiota.MethodsSewage samples were collected from the City of Houston for phages isolation. Samples were centrifuged, filtered and exposed to several targeted VRE host strains. After several amplification, the final filtrate was titrated and checked for the presence of VRE-specific phages. Isolated phages were observed under electron microscopy and were tested against multiple VRE strains isolated from different sources including patients’ stool samples, patients’ room environment, sewage samples, clinical isolates of daptomycin-resistant VRE strains or vancomycin-susceptible Enterococcus faecium (VSEF) and Enterococcus faecalis (VSEf) strains.ResultsFour VRE-specific phages were isolated from sewage samples (MDA1, MDA2, MDA3, and MDA4). All phages belong to the Caudovirales order. Phage MDA1 belongs to the Podoviridae family, phage MDA2 is a Siphoviridae, whereas MDA3 and MDA4 belong to the Myoviridae family (Figure 1A). All phages were lytic and were able to inhibit at least four VRE strains and only MDA1 had activity against VSEF and MDA4 against VSEf. The efficacy of these lytic phages complemented one another as the combination of these four phages inhibited all different VRE strains (Figure 1B).ConclusionOur results highlight the feasibility and the potential success of these phages in inhibiting VRE in vitro. These VRE-specific phage cocktails may be used in future studies to reduce VRE colonization and subsequent infections in HCT recipients. DisclosuresRoy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.

735. Bacteriophage Therapy Improves Survival of Galleria mellonella Larvae Injected with Vancomycin-Resistant Enterococcus faecium

BackgroundVancomycin-resistant Enterococcus faecium (VRE) is a major multidrug-resistant organism which may cause infection or colonization in hematopoietic cell transplant (HCT) patients. The use of VRE-specific bacteriophages (phages) may potentially help eradicate VRE colonization and subsequent infections. To test the efficacy and safety of phages against VRE in vivo, a cocktail combining four phages was used in a VRE-infected larva model.MethodsThe pre-screening model Greater Wax Galleria mellonella larva was used in this study. Larvae were infected with VRE by injecting a VRE strain isolated from stools of a VRE-colonized HCT patient at a concentration of 107 colony-forming units/10 μL. A single phage (MDA1) or a phage cocktail (MDA1, MDA2, MDA3, and MDA4) were also injected at a concentration of 106 colony-forming units/10 μL. Two model groups were tested; a prevention group (PG) and a treatment group (TG). For the PG, phages were administered 1 hour before bacterial injection whereas the TG were injected with phages 1 hour post bacterial injection. Control groups included larvae injected with bacteria alone, phages alone (to measure toxicity due to phage administration), sterile media (to measure any lethal effects due to physical trauma from the injection), or without any manipulation. Every group was composed of 5 larvae. The insect’s health state was observed and scored after 8 hours of incubation at 37ºC using a published health index scoring system.ResultsPhages improved survival of VRE-infected larvae (table). Only 32% of the VRE-infected larvae survived after 8 hours of infection whereas more than 80% survived when adding phages, whether phages were administered before or after VRE infection. The phage cocktail was shown to be more effective than the single phage MDA1 in improving survival (66% vs. 82% survival). Injecting larvae with phages alone was safe as the same survival rate was observed when compared with those injected with sterile media or those without manipulation.ConclusionThe use of larva model G. mellonella allows for rapid and efficient screening of the bacterial virulence and phage efficacy and safety. Such results highlight the feasibility and the potential impact of phage therapy on VRE colonization and infections. DisclosuresRoy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.

1559. Ertapenem Plus Ceftriaxone or Ceftaroline Dual Β-Lactam Combination for Enterococcus faecalis

BackgroundAmpicillin-ceftriaxone β-lactam therapy has become the standard of care for treating serious Enterococcus faecalis infections. Alternative regimens are of interest due to ceftriaxone’s association with C. difficile infections and VRE colonization, and ampicillin’s instability and inconvenient dosing schedule.Methods E. faecalis wild-type strain JH2-2 was utilized in a 48-hour in vitro pharmacodynamic model with a starting inoculum of 106 colony-forming units (CFU)/mL. Models were performed in duplicate to triplicate. Simulated doses of ertapenem 1g every 24 hours (fCmax 12.2 μg/mL; half-life 4 hours; MIC 4 μg/mL), ceftriaxone 2 g every 12 hours (fCmax 28.5 μg/mL; half-life 6.5 hours; MIC 512 μg/mL), and ceftaroline 600 mg every 8 hours (fCmax 27.1 μg/mL; half-life 2.7 hours; MIC 2 μg/mL) were tested. Ertapenem was also combined with ceftriaxone or ceftaroline. Bacterial counts were obtained at 0, 4, 8, 24, 32, and 48 hours. Bactericidal activity was defined as ≥ 3-log10 CFU/mL reduction from the initial inoculum. MICs were assessed at 0, 24, and 48 hours using E-tests in accordance with CLSI.ResultsErtapenem plus ceftriaxone, and ertapenem plus ceftaroline demonstrated bactericidal activity at 24 hours, but bacterial regrowth was observed at 48 hours (Table 1). An ertapenem MIC increase was only noted in one set of the ertapenem plus ceftriaxone models to 16mcg/mL at 48 hours, from 4mcg/mL at 0 hours. All other models did not have an increase in MIC.ConclusionBactericidal activity of ertapenem-based dual β-lactam combinations may prove to be an alternative treatment for severe E. faecalis infections. Mechanistic understanding of penicillin-binding protein (PBP) saturation and optimization of antimicrobial pharmacodynamics must be explored. Disclosures All authors: No reported disclosures.

2676. Effect of β-Lactam Allergy on Appropriateness of Antibiotic Use in Patients with Febrile Neutropenia

BackgroundOver 80% of patients with hematologic malignancies develop some form of infectious complication, most commonly febrile neutropenia. Patients with febrile neutropenia have 10% mortality, which increases if antibiotic administration is delayed past 30 minutes. Studies have suggested β-lactam allergy may delay administration of antibiotic while putting patients at greater risk for inappropriate antibiotic choice and adverse effects stemming from this. We sought to describe the risks associated with β-lactam allergy in the neutropenic population.MethodsWe conducted a retrospective, descriptive study from January 2016 to December 2017 identifying patients with febrile neutropenia and a reported history of β-lactam allergy. Baseline characteristics, allergy data, treatment data, and outcomes were collected and analyzed.ResultsWe identified 31 patients with febrile neutropenia and β-lactam allergy during this time period. Etiologies of neutropenia were hematologic malignancy (61.2%), stem cell transplantation (12.9%), solid-organ malignancy (22.6%), and autoimmune (3.3%). Reported reactions to β-lactams were rash (41.9%), hives (9.7%), anaphylaxis (3.2%), other (9.7%), and unknown (35.5%). Average time to antibiotic administration was 142.5 minutes. Antibiotic choice was cefepime (61.3%), piperacillin–tazobactam (6.5%), carbapenem (22.6%), fluoroquinolone (6.5%), cefepime and fluoroquinolone (3.2%), and vancomycin (58.1%). 51.6% received initial antibiotics consistent with the 2010 IDSA guidelines. Six patients underwent penicillin skin testing, all negative. 1 patient developed C. difficile infection, 1 developed MRSA colonization, and 3 developed VRE colonization. Mortality was 3.2% at 30 days and 16.1% at 90 days.ConclusionOur study estimated the antibiotic usage patterns and outcomes in patients with febrile neutropenia and reported β-lactam allergy. This showed low adherence to an established guideline for antibiotic choice in these patients. With rising antimicrobial resistance, there is a need to develop strategies to reduce inappropriate antimicrobial use, especially in patients with febrile neutropenia. Preemptive β-lactam allergy evaluation warrants further evaluation in the neutropenic population.Disclosures All authors: No reported disclosures.

670. VRE Clearance in Patients with Recurrent Clostridium difficile Infection Following Treatment with Microbiota-Based Drug RBX2660

BackgroundVancomycin-resistant Enterococcus (VRE) infection is frequently associated with immunocompromised and critically ill patients. VRE carriers are at increased risk for infection due to VRE colonization and they pose a risk as a transmission source. VRE infection and Clostridium difficile infection (CDI) share common risk factors, including disruption of the intestinal microbiome. Thus, therapeutic approaches that decolonize VRE would be valuable. Herein, we report on stool VRE clearance in a cohort analysis from a Phase 2 open-label study of RBX2660, standardized microbiota-based drug, for recurrent CDI.MethodsThis prospective, multicenter, open-label Phase 2 study enrolled subjects with recurrent CDI. Participants received up to 2 doses of RBX2660 delivered via enema with doses 7 days apart. Patients were requested to voluntarily submit stool samples at baseline and at 7, 30 and 60 days, 6, 12, and 24 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and gram staining. Vancomycin resistance was confirmed via blood agar and etest.ResultsStool samples were available for 143 patients. Twenty-one patients were VRE-positive at the first test (baseline or 7 day). Of the 19 VRE-positive patients that provided additional samples at later timepoints, 18 (94.7%) converted to negative as of the last available follow-up (30 or 60 days and 6, 12, or 24 months). The remaining patient remained positive at all follow-ups.ConclusionThis cohort analysis of VRE-positive patients within an rCDI population provides additional support that microbiota-based formulations, such as RBX2660, may have additional benefit beyond reducing the recurrence of CDI. Additional study is needed to confirm the role of microbiome restoration on VRE clearance.Disclosures All authors: No reported disclosures