Vancomycin-resistant Enterococci Bacteremia Research Articles

Emergence and Transmission of Daptomycin and Vancomycin-Resistant Enterococci Between Patients and Hospital Rooms.

Vancomycin-resistant enterococci (VRE) are a major cause of morbidity and mortality in immunocompromised patients. Tracking the dissemination of VRE strains is crucial to understand the dynamics of emergence and spread of VRE in the hospital setting. Whole genome sequencing (WGS) and phylogenetic analyses were performed to identify dominant VRE strains and potential transmission networks between 35 patients with VRE-positive rectal swabs and their rooms (main rooms and bathrooms) on the leukemia (LKM) and the hematopoietic cell transplant (HCT) floors. Sequence types (STs), drug resistance genes, and patients' outcomes were also determined. A total of 89 VRE strains grouped into 10 different STs, of which newly described STs were isolated from both floors (ST736, ST494, ST772, and ST1516). We observed highly genetically related strains transmitted between rooms, floors, and time periods in an average period of 39 days (ranging from 3 to 90 days). Of 5 VRE bacteremia events, 3 strains were lacking the pili operon fms14-17-13 (ST203) and the remaining 2 were resistant to daptomycin (DAP; ST736, ST664). Of 10 patients harboring DAP-resistant strains, only 2 were exposed to DAP within 4 months before strain recovery. Our comparisons of VRE strains derived from the environment and immunocompromised patients confirmed horizontal transfer of highly related genetic lineages of multidrug-resistant (particularly to DAP) VRE strains between HCT and LKM patients and their room environment. Implementing WGS can be useful in distinguishing VRE reservoirs where interventions can be targeted to prevent and control the spread of highly resistant organisms.

Evaluating Initial Empiric Therapy for Neutropenic Fever in Vancomycin-Resistant Enterococcus-Colonized Patients.

ObjectivesVancomycin-resistant enterococcus infections impact mortality in oncology patients. Given the low rate of vancomycin-resistant enterococcus bacteremia, low virulence of vancomycin-resistant enterococcus, and advent of rapid diagnostic systems, vancomycin-resistant enterococcus-directed empiric therapy in vancomycin-resistant enterococcus-colonized patients with neutropenic fever may be unnecessary, promoting increased antimicrobial resistance, drug-related toxicity, and cost.MethodsVancomycin-resistant enterococcus-colonized adults admitted for hematopoietic stem cell transplantation or induction therapy for acute leukemia/myeloid sarcoma with neutropenic fever were stratified by vancomycin-resistant enterococcus bacteremia development and empiric vancomycin-resistant enterococcus-directed antimicrobial strategy for first neutropenic fever (Empiric Therapy vs. non-Empiric Therapy). Primary endpoints included vancomycin-resistant enterococcus-related, in-hospital, and 100-day mortality rates. Secondary outcomes included vancomycin-resistant enterococcus bacteremia incidence for first neutropenic fever and the entire hospitalization, length of stay, Clostridioides difficile infection rate, and duration and cost of vancomycin-resistant enterococcus-directed therapy.ResultsDuring first neutropenic fever, 3 of 70 eligible patients (4%) developed vancomycin-resistant enterococcus bacteremia. Although all 3 (100%) were non-Empiric Therapy, no mortality (0%) occurred. Of 67 patients not developing vancomycin-resistant enterococcus bacteremia, 42 (63%) received Empiric Therapy and 25 (37%) non-Empiric Therapy. Empiric Therapy had significantly greater median duration (3 days vs. 0 days; P<.001) and cost ($1604 vs. $0; P<.001) of vancomycin-resistant enterococcus-directed therapy but demonstrated no significant differences in clinical outcomes.ConclusionAvailable data suggest Empiric Therapy may offer no clinical benefit to this population, regardless of whether vancomycin-resistant enterococcus is identified in blood culture or no pathogen is found. Such an approach may only expose the majority of patients to unnecessary vancomycin-resistant enterococcus-directed therapy and drug-related toxicities while increasing institutional drug and monitoring costs. Even in the few patients developing vancomycin-resistant enterococcus bacteremia, waiting until the organism is identified in culture to start directed therapy likely makes no difference in mortality. This lack of benefit warrants consideration to potentially omit empiric vancomycin-resistant enterococcus-directed therapy in first neutropenic fever in many of these patients.

&lt;p&gt;Predictors of Mortality in Patients with Carbapenem-Resistant Gram-Negative Bacilli or Vancomycin-Resistant Enterococci Bacteremia&lt;/p&gt;

PurposeThe incidences of carbapenem-resistant gram-negative bacilli (CRGNB) and vancomycin-resistant Enterococci (VRE) have increased rapidly in South Korea since 2000. The mortality rate for CRGNB or VRE bacteremia cases is higher than that for non-resistant bacteremia cases. The factors associated with higher mortality are unclear. We investigated the factors associated with mortality from CRGNB or VRE bacteremia and compared the relative risk of these factors.Patients and MethodsWe retrospectively collected data from adult patients with CRGNB or VRE bacteremia. Patients were grouped according to whether they survived or died. The data from both groups were compared.ResultsDuring the study period, 171 cases of CRGNB or VRE bacteremia were identified, of which 100 were CRGNB bacteremia cases and 71 were VRE bacteremia cases. Multivariate analysis revealed significant associations with Pitt bacteremia score (PBS) (odds ratio [OR] 1.329, 95% confidence interval [CI] 1.049–1.684). In the multivariate analysis, negative conversion of follow-up blood culture (FUBC) was related with one-week mortality from CRGNB or VRE bacteremia (OR 17.623, 95% CI 5.726–54.244). In the multivariate analysis of risk factors for 28-day mortality for CRGNB or VRE bacteremia, the significant risk factors were bacteremia of respiratory origin (OR 4.491, 95% CI 1.622–12.435) and positive FUBC (OR 4.082, 95% CI 1.626–10.204).ConclusionDespite the high mortality rate in patients with CRGNB or VRE bacteremia, the related mortality could be predicted by independent risk factors of PBS, positive FUBC, and bacteremia of respiratory origin.

VRE Screening and Isolation: One Size Does Not Fit All

Background: The need for screening and isolation for patients colonized with vancomycin-resistant Enterococcus (VRE) remains controversial. In this study, we examined the effects of discontinuation and reinstatement of these practices on VRE infection and colonization incidence within a multisite, tertiary-care hospital center, including its effects on specific at-risk groups. Methods: We retrospective analyzed VRE clinical isolate, infection, and bacteremia incidence rates at our hospital (1) prior to discontinuation of universal screening and isolation (January 2010–June 2012), (2) during discontinuation (July 2012–April 2017), and (3) after reinstatement of screening and isolation in high-risk wards (intensive care and multiple-organ transplant units, June 2017–April 2019). Monthly incidence rates were calculated for each of 3 sites at our tertiary-care hospital: site A, which includes the transplant program, site B, an adult cancer hospital, and site C, which includes orthopedic and neurology programs. To understand the differential effect of screening and isolation on various risk groups, incidence rates were also calculated for individual programs within our hospital, including medicine, surgery, intensive care, oncology, and transplant programs. Results: During the period of study, 3,167 cases of VRE isolates were identified. Patient colonizations of VRE across the institution increased throughout the study period, with the monthly number of newly colonized patients increasing from 10.4 in the first period of study to 20.6 in the last period. The overall VRE clinical isolate, infection, and bacteremia incidence rates did not increase following the cessation of VRE screening and isolation precautions; however, a significant increase was seen among the patients at site B (Fig. 1, infection rates). Furthermore, there was a significant decrease in VRE clinical isolate, infection, and bacteremia incidence following the reinstatement of screening in the ICU and transplant programs at site A, but no effect was seen in the other programs (Fig. 2, infection rates). Conclusions: The risk associated with discontinuing VRE screening and isolation measures appears depend on the subgroup of patients within a hospital environment. Furthermore, risk-based or unit-based VRE screening and isolation appears to be effective at controlling VRE incidence, even after measures had previously been discontinued. Additional study of other inpatient settings is warranted to determine the effects of screening and isolation for VRE on other patient subgroups.Funding: NoneDisclosures: Susy Hota reports contract research for Finch Therapeutics.

Risk factors for development of vancomycin-resistant enterococcal bacteremia among VRE colonizers : Aretrospective case control study.

We aimed to determine the proportion of vancomycin-resistant enterococci (VRE) colonized patients among all inpatients who later developed VRE bacteremia during hospital stay and to identify the risk factors for VRE bacteremia at atertiary hospital. Patients with positive rectal screening or any clinically significant positive culture results for VRE were included in 1‑year follow-up. Colonization with VRE was defined as apositive culture (rectal, stool, urinary) for VRE without infection and VRE bacteremia was defined as positive blood culture if the signs and symptoms were compatible with infection. To determine the risk factors for VRE bacteremia among VRE colonized patients, aretrospective case control study was performed. The two groups were compared in terms of variables previously defined as risk factors in the literature. Of 947 positive samples, 17VRE bacteremia were included in the analysis. Cephalosporin use for more than 3days within 3months was asignificant risk factor for bacteremia (p = 0.008). Prior use of carbapenems was found to be statistically significant for bacteremia (p = 0.007). In multivariate analyses the use of carbapenems and cephalosporins was an independent risk factor for developing bacteremia among VRE colonizers (odds ratio, OR, 6.67; 95% confidence interval, CI, 1.30-34; p = 0.022 and OR 4.32, 95% CI 1.23-15; p = 0.022, respectively). AVRE colonization in patients receiving broad-spectrum beta-lactam antibiotics including carbapenems and cephalosporins may result in bacteremia. It is possible to keep mortality at very low levels in VRE bacteremia with effective infection control measures, rapid infectious diseases consultation and rational antimicrobial treatment based on current epidemiological data.

Impact of Inappropriate Antibiotic Therapy in Vancomycin-Resistant Enterococcus Bacteremia.

Vancomycin-resistant Enterococcus (VRE) bacteremia has significant morbidity and mortality. Empiric antibiotic regimens for treating patients with risk factors for multidrug-resistant organisms may not have medications directed at treating VRE. To evaluate the impact of antibiotic therapy (and other risk factors) on mortality in VRE bacteremia. We identified 146 patients with VRE bacteremia, admitted at our institution over an 11 years period (2004-2014). All inpatients with an initial positive VRE blood culture were included only once in the analysis. Eighteen patients were excluded from the study because of inability to retrieve medical information regarding one or more important study variables. The retrospectively collected data from electronic medical records of 128 patients were analyzed. The inpatient, 30-day, and 1-year mortality rates from VRE bacteremia were 23%, 31%, and 59%, respectively. Only 19% patients were discharged home. Inappropriate antibiotics were prescribed in 19% patients. Appropriate antibiotics were prescribed in 81% patients (62% daptomycin and 37% linezolid); however, only 58% patients received appropriate antibiotics within 24 hours of the reported positive blood cultures. The 30-day and 1-year mortality rates for patients treated with inappropriate antibiotics were 54% and 67% compared with 26% and 50%, respectively, for those treated with appropriate antibiotics. The median survival rate for patients treated with inappropriate antibiotics was 1 month (95% confidence interval: 0.0-1.0) compared with 11 months (95% confidence interval: 4.0-13.0) for those treated with appropriate antibiotics. The advanced patient age (median age 75 years vs. 63 years) was a significant risk factor for inappropriate antibiotic therapy (P value = 0.02). The multivariate Cox regression model revealed inappropriate antibiotic therapy (P value = 0.003), septic shock (P value = 0.0004), albumin (P value = 0.04), and dementia (P value = 0.003) to be associated with 30-day mortality. Our study highlights the detrimental effect of inappropriate antibiotic therapy and other risk factors on morbidity and mortality associated with VRE bacteremia.

Daptomycin perioperative prophylaxis for the prevention of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients.

Vancomycin-resistant Enterococcus (VRE)-colonized liver transplantation (LT) recipients have increased post-LT morbidity, mortality, and higher rates of VRE infections compared with their non-colonized counterparts. Pre-LT screening for VRE colonization and inclusion of daptomycin in the perioperative antibiotic prophylaxis regimen may mitigate this risk. We performed a retrospective chart review of liver transplant recipients aged≥18years between 2013 and August 2019 to identify pre-LT VRE-colonized recipients and whether they received daptomycin perioperative prophylaxis (DPP). Demographic and clinical characteristics, including risk factors for VRE infection, were collected. Outcomes measured were VRE-related infection and all-cause mortality within 90days of LT. Of the 27 VRE-colonized liver transplant recipients within the study period, 25 received DPP. All recipients were admitted to the intensive care unit postoperatively, six (24%) required reoperation, fifteen (60%) required renal replacement therapy, and eight (32%) experienced postoperative hemorrhage within 90days post-transplant. Two recipients (8%) experienced acute cellular rejection, but no primary graft failure was seen within 90days. Among those who received DPP, no infections related to VRE or death was seen within 90days of LT. The two VRE-colonized recipients who did not receive DPP both developed VRE bacteremia in the early post-LT period. Despite having multiple risk factors for post-LT VRE infection, VRE-colonized recipients who received DPP did not develop VRE-related infections in the first 90days post-LT. Our experience demonstrates that pre-LT VRE screening and DPP may be associated with a reduction in VRE infection in the early post-LT period, but this strategy warrants further evaluation in prospective studies.

574. Reporting of Vancomycin-Resistant Enterococcus Bacteremia among National Healthcare Safety Network Acute Care Hospitals

BackgroundThe National Healthcare Safety Network’s (NHSN’s) Multidrug-resistant Organism/Clostridioides difficile (MDRO/CDI) Module serves as a surveillance platform for tracking antibiotic-resistant laboratory-identified (LabID) organisms. LabID event surveillance, which does not require submission of clinical data to NHSN, provides proxy measures for MDRO burden. While surveillance of some organisms is federally mandated, these requirements do not extend to vancomycin-resistant Enterococcus (VRE). We sought to describe the extent of acute care hospital (ACH) participation in NHSN VRE surveillance and identify facility-level factors associated with VRE bacteremia. These could explain differences in VRE incidence and be used in preparation for a national risk-adjusted benchmark.MethodsACHs that reported at least one month of facility-wide inpatient (FacWideIN) VRE bacteremia LabID Event data to NHSN in 2017 were included in the analysis. LabID events were categorized as healthcare facility-onset (HO), defined as a laboratory result for a specimen collected ≥4 days after admission, or community-onset (CO), defined as a specimen collected < 4 days after admission. Monthly patient day and admission denominators were used to calculate FacWideIN HO incidence and CO prevalence rates. Univariate analyses were performed on facility-level factors from NHSN’s annual hospital survey to assess their relationship with HO VRE bacteremia.ResultsA total of 544 HO VRE bacteremia events were reported by 498 hospitals in 37 states. About 67% of reporting hospitals were located in California. The national rate of HO VRE bacteremia was 0.27 per 10,000 patient-days and the CO VRE bacteremia rate was 0.58 per 10,000 admissions. Major medical school affiliation, hospital type, larger number of beds and ICU beds, longer average length of stay and the presence of an oncology unit were significantly associated with HO VRE bacteremia (Table 1).ConclusionBased on the VRE data reported to NHSN, certain facility-level factors may contribute to a higher incidence of HO VRE bacteremia. Future analyses can allow us to determine whether these factors are independently associated with VRE. Risk-adjusted surveillance data can help guide facilities and states to compare their burden of VRE to a national benchmark. Disclosures All authors: No reported disclosures.

1527. Clinical Variables Associated with Vancomycin Resistance in Children with Bacteremia Due to Enterococcus spp.

Background Enterococcus spp. (E) is an important cause of nosocomial bacteremia. The emergence of vancomycin-resistant E in the nosocomial setting conditions the empirical treatment and limits therapeutic options.MethodsA retrospective cohort study of children ≥1 month with E bacteremia in a reference pediatric hospital was performed. Study period January 1, 2016–December 31, 2018. Outcome: to describe clinical and epidemiological characteristics of children with bacteremia due to Enterococcus spp. resistant to vancomycin (VRE) vs. sensitive (VSE). Identify variables associated with VRE. STATA 13 was used.Results N = 82 patients. Median age was 37.6 months (IQR 2–48), 45 patients (54.9%) were male; 76 patients (92.7%) had underlying disease (intestinal failure (21.9%), heart disease (17.1%), preterm births (12.2%), hematological disease (10.9%), and liver failure (7.3%); 16 patients (19.5%) received immunosuppressive therapy. Sixty bacteremia (73.2%) were by E. faecalis and 22 (26, 8%) by E. faecium. Vancomycin resistance was documented in 13 patients (15.8%), all of which were E. faecium. In the bivariate analysis, patients with VRE bacteremia were significantly older in months than those with VSE bacteremia [75.4 (IQR 6–151) vs. 30.5 (IQR 2–33), P <0.02]; had more frequency of previous colonization with VRE [n: 8 (61.5%) vs. n: 4 (5.8%) P < 0.001], hematological disease [n: 5 (38.5%) vs. n: 5 (5.8%), P = 0.01], liver failure [n: 3 (23.1%) vs. n: 3 (4.4%), P = 0.02] and immunosuppressive therapy [n: 6 (46.2%) vs. n: 10 (14.5%) P = 0.008]. Patients with VRE bacteremia had a lower median white blood cell count [7040 (IQR 2150–10250) vs. 14474 (IQR 6160–17090), P <0.03]. Mortality in P with VRE was 15.4% (n: 2) and 4.3% in P with VSE (n: 3), P = 0.1. No statistically significant differences were found according to history of surgery, previous hospitalization, antibiotic therapy in the last 3 months or clinical presentation. In the multivariate model, predictors of VRE bacteremia adjusted for the rest of the significant variables were hematological disease OR 11.1 (95% CI 2.3–53.8) P = 0.003, and liver failure OR 7.7 (95% CI 1.2–50.4), P = 0.03.ConclusionIn this cohort of children with enterococcal bacteremia, hematological disease and liver failure were predictive variables of VRE bacteremia.Disclosures All authors: No reported disclosures.

575. Evaluation of Risk Factors and Clinical Outcomes of Patients with Vancomycin-Resistant Enterococcus Infections

BackgroundVancomycin-resistant Enterococci (VRE) occurs with enhanced frequency in hospitalized patients and are usually associated with poor clinical outcomes. The purpose of this study was to evaluate the risk factors and clinical outcomes of patients with VRE infections.MethodsThis study was an IRB-approved multi-center retrospective chart review conducted at a three-hospital health system between August 2016-November 2018. Inclusion criteria were patients ≥18 years and admitted for ≥24 hours with cultures positive for VRE. Patients pregnant or colonized with VRE were excluded. The primary endpoint was to analyze the association of potential risk factors with all-cause in-hospital mortality (ACM) and 30-day readmission. The subgroup analysis focused on the association of risk factors with VRE bacteremia. The secondary endpoint was to evaluate the impact of different treatment groups of high dose daptomycin (HDD) (≥10 mg/kg/day) vs. low dose daptomycin (LDD) (< 10 mg/kg/day) vs. linezolid (LZD) on ACM and 30-day readmission. Subgroup analysis focused on the difference of length of stay (LOS), length of therapy (LOT), duration of bacteremia (DOB) and clinical success (CS) between the treatment groups.ResultsThere were 81 patients included for analysis; overall mortality was observed at 16%. Utilizing multivariate logistic regression analyses, patients presenting from long-term care facilities (LTCF) were found to have increased risk for mortality (OR 4.125, 95% CI 1.149–14.814). No specific risk factors were associated with 30-day readmission. Patients with previous exposure to fluoroquinolones (FQ) and cephalosporins (CPS), nosocomial exposure and history of heart failure (HF) showed association with VRE bacteremia. ACM was similar between HDD vs. LDD vs. LZD (16.7% vs. 15.4% vs. 0%, P = 0.52). No differences were seen between LOS, LOT, CS, and DOB between the groups.ConclusionAdmission from LTCFs was a risk factor associated with in-hospital mortality in VRE patients. Individuals with history of FQ, CPS and nosocomial exposure as well as history of HF showed increased risk of acquiring VRE bacteremia. There was no difference in ACM, LOS, LOT, and DOB between HDD, LDD and LZD.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.

622. The Accessory Genome in Enterococcal Bacteremia: Results from the Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS)

BackgroundVancomycin-resistant enterococci (VRE) are a major cause of nosocomial bloodstream infections. Enterococci exhibit remarkable genomic plasticity and can recombine through the acquisition of genetic material via mobile genetic elements (MGEs), including resistance genes. The accessory genome plays a major role in the evolution of enterococci within the human host. Thus, dissecting the entire genome (pan-genome) is of paramount importance to characterize the population structure of enterococci causing disease.MethodsVENOUS is an ongoing prospective, observational study of adults with enterococcal bacteremia. From September 2016 to March 2018, E. faecalis (Efs) and E. faecium (Efm) were collected in 14 hospitals of a single hospital system and a major cancer center in Houston, TX, and a general hospital in Detroit, MI. Short- and long-read genomic sequencing were performed with Illumina MiSeq and Oxford Nanopore Technologies GridION X5, respectively. A proprietary bioinformatics pipeline was utilized for genome assembly and further analyses.Results156 Efs and 98 Efm isolates from single patients were analyzed. The average proportion of core genes in each genome was 64.6% (53.0–74.1) and 49.1% (45.2–51.0) for Efs and Efm, respectively. The vanA gene cluster was identified in 5.1% (8/157) of Efs and 57.1% (56/98) of Efm. The plasmid-encoded aac(6′)-Ie-aph(2″)-Ia gene conferring high-level resistance to aminoglycosides was found in 37.6% (59/157) Efs, seven of which also possessed vanA. Long-read sequencing of vanA-harboring plasmids from a subset of VRE revealed that the vanA cluster was carried in plasmids ranging from 31.7 to 132.3 kb. Although the vanA operon was fairly conserved, insertions of MGE were identified in the intergenic regions of vanS/vanH and vanX/vanY. Furthermore, a variety of MGE insertions mediated integration of the vanA operon, including IS1216 and IS256 (figure).ConclusionAccessory genes, including AMR genes, comprise a significant proportion of the enterococcal pan-genome, indicating major genetic plasticity within these organisms. Acquired resistance genes seem to have a high degree of recombination and play a substantial role in the expansion of the genomic repertoire in clinical isolates. DisclosuresSamuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.

Efficacy and safety of daptomycin versus linezolid treatment in patients with vancomycin-resistant enterococcal bacteraemia: An updated systematic review and meta-analysis

ObjectivesA systematic review and meta-analysis were conducted to re-assess the efficacy and safety of daptomycin compared with linezolid treatment for vancomycin-resistant enterococcal (VRE) bacteraemia and to explore whether high-dose daptomycin is beneficial. MethodsPubMed, EMBASE, the Cochrane Library, and meeting abstracts were searched from inception to February 2019. Studies evaluating daptomycin and linezolid treatment for VRE bacteraemia were included. ResultsTwenty-two observational studies were identified. A non-significant higher mortality (OR 1.27; 95% CI 0.99–1.63) and significantly lower risk of thrombocytopenia (OR 0.78; 95% CI 0.61–0.99) were found with daptomycin compared with linezolid treatment. Clinical response (OR 0.88; 95% CI 0.59–1.33), microbiological cure (OR 0.82; 95% CI 0.53–1.28), recurrence of bacteraemia (OR 0.96; 95% CI 0.70–1.32), and risk of creatine kinase elevation (OR 0.82; 95% CI 0.46–1.47) were similar for the two agents. In the subgroup analysis of studies focusing on high-dose daptomycin treatment, similar mortality was observed (OR 0.92; 95% CI 0.46–1.84). Moreover, patients receiving daptomycin tended to show a higher clinical response (OR 1.61; 95% CI 0.37–7.09) and microbiological cure (OR 2.09; 95% CI 0.43–10.1) and a lower risk of bacteraemia relapse (OR 0.47; 95% CI 0.15–1.45), although the difference was not significant. ConclusionsCompared with linezolid treatment, daptomycin treatment showed comparable clinical and microbiological outcomes but a lower incidence of thrombocytopenia. Because of the dose-dependent effect that was observed, high-dose daptomycin should be considered for patients with VRE bacteraemia.

184 Cost-Effective Analysis of Prophylactic Oral Vancomycin Use to Prevent Recurrent Clostridium difficile Infections in Hospitalized Patients

INTRODUCTION: Clostridium difficile infections (CDI) is the single largest cause of morbidity and mortality among hospital acquired infections and is characterized by frequent recurrence. In the hospital setting, CDI tends to occur in patients with predisposing risk factors such as advanced age, prolonged stay, and exposure to systemic antibiotics. Although antimicrobial agents are major risk factors for CDI, their use in patients is often necessary and inevitable. There is an emerging practice of giving prophylactic oral vancomycin as secondary prophylaxis to prevent recurrent CDI. Prior published retrospective cohort studies suggest patients on systemic antimicrobial therapy who received prophylactic oral vancomycin had significantly lower rates of recurrent CDI compared to patients who did not receive the prophylaxis. However, the cost effectiveness of oral vancomycin used as secondary prophylaxis to prevent recurrent CDI is unknown. METHODS: We programmed a Markov Chain Monte Carlo simulation analytic model using published literature and national databases. For each scenario, 500 patients were simulated. The base case was modeled as a hypothetic cohort of hospitalized patients with a history of CDI, currently receiving systemic antimicrobial therapy, who either received or did not receive secondary prophylactic oral vancomycin. Projected outcomes included cost (US dollars). 2-way sensitivity analyses were conducted. A P-value less than 0.05 was considered significant. RESULTS: Across 500 simulations, prophylactic oral vancomycin resulted in a greater cost compared to no oral vancomycin at $12,045.67, 95% CI = [11880.80–12210.53] and $8,135.48, 95% CI = [8,047.37–8,223.58], respectively (Figure 1). The difference was statistically significant (P value &lt;1 × 10−6). The treatment arm with oral vancomycin also resulted in approximately a 2.45 increased risk of mortality compared to patients who did not receive vancomycin. CONCLUSION: Our findings suggest that prophylactic oral vancomycin may not be a cost-effective strategy in reducing the incidence of CDI recurrence and may, in fact, be associated with an increased risk of mortality in hospitalized patients receiving high dose systemic antimicrobial therapy. These findings appear to be largely driven by the risk of developing vancomycin resistant enterococcus (VRE) infections, namely VRE bacteremia which is associated with high economic burden and increased mortality.

3235 Black Stomach: A Rare Clinical Entity in a Patient With Recurrent Primary Sclerosing Cholangitis With Cirrhosis

INTRODUCTION: Acute gastric necrosis is rarely encountered given the stomach's rich vascular distribution and collateral circulation. Reported causes of gastric necrosis include gastric outlet obstruction, intrathoracic herniation, ingestion of caustic substances, anorexia nervosa and bulimia, and systemic hypotension. We present a case of “black stomach” secondary to persistent shock in the setting of end-stage liver disease. CASE DESCRIPTION/METHODS: A 33-year-old female with a history of primary sclerosing cholangitis status post orthotopic liver transplant in 2017 was initially hospitalized for pneumonia complicated by worsening graft function (MELD 38). Liver biopsy confirmed recurrent PSC with cirrhosis. Her course deteriorated after developing multiple episodes of coffee-ground emesis and melena requiring pressors. Initial EGD showed mild portal hypertensive gastropathy and two, 5 mm clean-based ulcers in the gastric antrum. No esophageal varices were visualized. Despite medical therapy, her melena and hypotension continued, leading to acute renal failure requiring CVVH. Repeat EGD two days later showed an adherent clot in the gastric fundus and severe portal hypertensive gastropathy with spontaneous oozing. Despite supportive measures, she continued to have melena. A third EGD showed a large blood clot in the fundus that was unable to be removed. Friable mucosa was noted throughout, as well as a non-healing, clean-based antral ulcer. Two days later, a fourth EGD revealed mucosa in the fundus and proximal body that appeared black and diffusely necrotic with sloughing of mucosa, with normal mucosa distally. The patient was not a candidate for IR embolization, TIPS procedure or surgery. One week later, she decompensated and died of septic shock from VRE bacteremia. DISCUSSION: Our case demonstrates that persistent gastric ischemia in the setting of shock and underlying end-stage liver disease results in gastric necrosis noted endoscopically over the course of a week. It is possible that the patient's underlying decompensated graft cirrhosis predisposed her to developing segmental gastric necrosis and “black stomach” in the area supplied and drained by the left gastric vessels, which can be affected by shock and portal congestion. Despite aggressive measures and supportive care, gastric necrosis carries a high morbidity and mortality. Therefore, a high index of clinical suspicion is required to make an early diagnosis in order to guide potential therapeutic interventions in such critically ill patients.

TWO HITS FOR LACTIC ACIDOSIS: A STUDY IN DRUG-DRUG INTERACTION

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Tumors with high mitotic activity undergo oxidative phosphorylation for ATP synthesis. In acute myelogenous leukemia (AML) new therapies that target energy metabolism and mitochondrial protein synthesis are being studied. When these new drugs are combined with medications that also effect mitochondrial activity serious complications may occur. Particularly when side-effects from new investigation therapies are not widely known, nor available to automated electronic medical record (EMR) drug interaction checks. We present a case of life-threatening lactic acidosis due to the use of a STAT3 (signal transduction activator of transcription) inhibitor - a drug currently in clinical trials -- in a patient also receiving linezolid, in whom the risk of a life-threatening drug interaction and toxicity was not fully appreciated. CASE PRESENTATION: A 61 year-old man with a history of refractory AML in a clinical trial with a STAT 3 inhibitor presented with sepsis, but despite appropriate antibiotics his clinical status declined requiring mechanical ventilation. Lab studies showed a rapidly worsening lactic acidosis (3.9 to 18 mmol/L) over a few hours. Later it was discovered that he had completed a prolonged course of linezolid for vancomycin-resistant enterococcus bacteremia the day prior to admission. Though inputted in the medical record as an investigation study drug, the drug-drug interaction with linezolid was not registered by the EMR. Plasmapheresis and dialysis were used to remove residual linezolid and the study drug. Subsequently his lactate decreased to 2.4 and he was extubated. However, given the lack of treatment options for refractory AML the family decided to pursue comfort measures. DISCUSSION: STAT3 is a member of the STAT family of proteins involved in intracellular and extracellular signals to the nucleus, controlling gene expression. STAT3 is involved in AML cells, antiapoptosis genes, cell cycle regulators and promotes OXPHOS (oxidative phosphorylation). A major concern for the use of OXPHOS inhibitors is lactic acidosis. Similarly, linezolid decreases mitochondrial respiratory chain enzyme activity, hence disrupting cellular energy production. In our patient, it is likely that the use of two OXPHOS inhibitors resulted in severe mitochondrial toxicity and lactic acidosis. With new medications being developed that inhibit mitochondrial oxidative phosphorylation, intensive care units may see patients who are suffering from their side effects. CONCLUSIONS: This case highlights the importance of reviewing mechanisms and adverse effects of study drugs. Our case also reminds us that study drugs may not be included in the EMR or not flagged by computerized drug interaction alerts. We believe the use of STAT3 inhibitor and other new OXPHOS inhibitors warrant careful monitoring, particularly when used simultaneously with other medications that increase the risk of mitochondrial toxicity. Reference #1: Redell MS, Ruiz MJ, Alonzo TA, Gerbing RB, Tweardy DJ. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011;117(21):5701-9. DISCLOSURES: No relevant relationships by Alan Gandler, source=Web Response No relevant relationships by Alexys Monoson, source=Web Response No relevant relationships by David Oxman, source=Web Response No relevant relationships by MRINALINI VENKATA SUBRAMANI, source=Web Response

The impact of discontinuing contact precautions for multidrug resistant organisms at a less than 400-bed level II teaching hospital and a community hospital: A 3-month pilot study

The impact of discontinuing contact precautions (CPs) for patients with select multidrug-resistant organisms on bacteremia infection rates was evaluated in this quality improvement project. The removal of use of CPs, with increased focus on standard precautions, for all patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) colonization/infection was piloted via a quality improvement project over a 3-month period. CP was discontinued in December 2018. Comparing 3 months pre- and postchange, the overall incidence density rate decreased for hospital-onset (HO) laboratory-identified (LabID) MRSA bacteremia (0.07 vs 0.02; P = .52), whereas HO LabID VRE bacteremia rates remained the same (0.00 vs 0.00). Overall estimated financial savings, including personal protective equipment ($15,375) and staff time ($17,165), was $32,540 for the project period, with annualized estimated savings of $130,160. In this pilot study evaluating the discontinuance of CPs, there was no evidence of an increase in HO MRSA or VRE LabID bacteremia incidence density rates. This practice change may be safely implemented at similar health care facilities.

Impact of Enterococcal Bacteremia in Liver Transplant Recipients

BackgroundEnterococcus species are a common cause of bacteremia in liver transplant recipients. Vancomycin-resistant enterococci (VRE) have become an important cause of nosocomial infection. In this study, we analyzed the incidence, antibiotic resistance, and outcomes of enterococcal bacteremia in living donor liver transplant recipients and the risk factors for VRE. Patients and MethodsThis single-center, retrospective review included 536 patients who underwent liver transplant between January 2008 and December 2017. ResultsAmong 536 patients, 42 (7.8%) experienced a total of 58 enterococcal bacteremic episodes (37 Enterococcus faecium, 17 Enterococcus faecalis, 2 Enterococcus casseliflavus, 1 Enterococcus. avium, and 1 Enterococcus raffinosus). Most cases of enterococcal bacteremia (46/58, 79.3%) occurred within 6 months after transplant; among the 26 cases of VRE bacteremia, 50% occurred within 1 month after transplant. E. faecium isolates had the highest rate of vancomycin resistance (25/37, 67.5%), whereas all E. faecalis isolates were susceptible to vancomycin. According to multivariate analysis, post-transplant dialysis (odds ratio, 3.95; 95% CI, 1.51–10.34; P = .005) and length of post-transplant hospital stay (odds ratio, 1.03; 95% CI, 1.009–1.04; P = .004) were significantly associated with VRE bacteremia. One-year mortality was 31% (13/42) among recipients with enterococcal bacteremia, 5.0% (20/384) among nonbacteremic patients, and 11.1% (10/90) among patients with nonenterococcal bacteremia (P < .001). ConclusionIn this study, enterococcal bacteremia showed high incidence in liver transplant recipients, especially with vancomycin resistance, occurred in early period after transplant, and was associated with increased mortality. High rates of resistance to vancomycin warrant further efforts to manage enterococcal infection in liver transplant recipients at our center.

PB2323 CORRELATION BETWEEN COLONIZATION AND BACTERAEMIA FROM MULTIDRUG RESISTANT SPECIES IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION

Background: Bacterial infections from multidrug resistant pathogens are an important cause of morbidity and mortality of patients undergoing hematopoietic cell transplantation (HCT). Aims: Aim of this study was to record bacteremia's from multidrug-resistant bacteria in the first hospitalized period of transplantation and their correlation with the patient's colonization. Methods: The prospective analysis includes 24 consecutive patients (14 males, 10 females), with median age of 45 years (range 24-72) who underwent HCT (21 allogeneic, 3 autologous) during 1/1/2018-15/8/2018. All patients were tested for colonization from multidrug resistant Klebsiella Pneumoniae Carbapenemase (KPC+) and Vancomycin Resistant Enterococcus (VRE+) with rectal smear and urine culture upon their hospitalization in the unit and before the start of the conditioning regimen. All patients received ciprofloxacin prophylaxis. We analyzed the bacteremia's during the first hospitalization in the Bone Marrow Transplantation Unit, approximately until day 30 after transplantation. Results: Twelve from 24 (50%) patients were found colonized with multidrug resistant pathogens upon their entry into the unit (Table 1). A total of 19 different bacteremia's occurred in 13 patients. Of the 9 non-colonized patients’ no one experienced episode of multidrug resistant KPC or VRE bacteremia. From the 6 KPC+ patients, all of them (100%) showed bacteremia, 3/6 (50%) KPC bacteremia and 3/6 bacteremia from other pathogen than KPC (Pseudomonas Aeruginosa-MBL, Staph. Epidermidis). Of the 9 VRE+ patients, 4 showed bacteremia and none (0%) showed VRE bacteremia. No mortality due to bacteremia was observed.Summary/Conclusion: There is a high rate of colonization from multi-resistant KPC and VRE in heavily treated patients referred for transplantation. Non-colonized patients did not experience KPC or VRE bacteremia, reflecting high prophylactic measures in a transplant unit. KPC colonization is associated with a remarkable (50%) probability of bacteremia from the same multidrug resistant pathogen. Our results demonstrate the importance of urine and rectal smear control for colonization with KPC in patients who are going to receive HSCT, as this can be used for targeted antibiotic treatment in case of the occurrence of febrile neutropenia

Comparative Efficacies of Linezolid vs. Tedizolid in an Experimental Murine Model of Vancomycin-Resistant Enterococcal (VRE) Bacteremia.

Tedizolid (TZD) is an oxazolidinone derivative which demonstrates bacteriostatic activity through inhibition of protein synthesis. We compared the efficacies of TZD and an earlier-generation oxazolidinone, linezolid (LZD), in an experimental murine model of bacteremia caused by two VRE strains (one each E. faecium and E. faecalis). LZD exhibited significantly better efficacy in terms of reduced VRE blood and target tissue densities than TZD in this model.