Vancomycin-resistant Enterococci Bloodstream Infections Research Articles

What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream Infections?

What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream Infections?

Practical methods for effective vancomycin-resistant enterococci (VRE) surveillance: experience in a liver transplant surgical intensive care unit.

We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling. Prospective, patient-level surveillance program of incident VRE colonization. Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.PatientsAll patients admitted to the SICU from June to August 2015. We conducted a point-prevalence estimate followed by admission and weekly surveillance by perirectal swabbing and/or stool sampling. Incident colonization was defined as a negative screen followed by positive surveillance. VRE was detected by culture on Remel Spectra VRE chromogenic agar. Microbiologically-confirmed VRE bloodstream infections (BSIs) were tracked for 2 months. Statistical analyses were calculated using the McNemar test, the Fisher exact test, the t test, and the χ2 test. In total, 91 patients underwent VRE surveillance testing. The point prevalence of VRE colonization was 60.9%; VRE prevalence on admission was 30.1%. Weekly surveillance identified an additional 7 of 28 patients (25.0%) with incident colonization. VRE BSIs were more common in VRE-colonized patients than in noncolonized patients (8 of 43 vs 2 of 48; P=.028). In a direct comparison, perirectal swabs were more sensitive than stool samples in detecting VRE (64 of 67 vs 56 of 67; P=.023). Compliance with perirectal swabbing was 89% (201 of 226) compared to 56% (127 of 226) for stool collection (P≤0.001). We recommend weekly VRE surveillance over admission-only screening in high-burden units such as liver transplant SICUs. Perirectal swabs had greater collection compliance and sensitivity than stool samples, making them the preferred methodology. Further work may have implications for antimicrobial stewardship and infection control.

Risk factors for intestinal colonization with vancomycin resistant enterococci' A prospective study in a level III pediatric intensive care unit.

PURPOSE:Vancomycin-resistant enterococci (VRE) emerged as one of the major nosocomial pathogens across the globe. Gut colonization rate with VRE is higher in patients admitted to intensive care units (ICUs) due to the higher antibiotic pressure. VRE colonization increases the risk of developing infection up to 5–10 folds. The aim of this study was to determine the rates of VRE colonization among the patients admitted to pediatric ICU (PICU) and risk factors associated with it.MATERIALS AND METHODS:Rectal swabs were collected after 48 h of admission to PICU from 198 patients. The samples were inoculated onto bile esculin sodium azide agar with 6 mg/ml of vancomycin. Growth on this medium was identified by the standard biochemical test, and minimum inhibitory concentration of vancomycin and teicoplanin was detected by agar dilution method. Resistance genes for vancomycin were detected by polymerase chain reaction. Risk factors were assessed by logistic regression analysis.RESULTS:The rates of VRE colonization in patients admitted to PICU was 18.6%. The majority of the isolates were Enterococcus faecium (75.6%) followed by Enterococcus faecalis (24.4%). One patient acquired a VRE bloodstream infection (2.6%) among colonized patients, and none of the noncolonized patients acquired the infection. Consumption of vancomycin was found to be the only risk factor significantly associated with VRE colonization.CONCLUSION:Routine surveillance and isolation of patients found to be VRE colonized may not be possible in tertiary care hospitals; however, educating health-care workers, promoting handwashing with antiseptic soaps or solutions, and antibiotic Stewardship policy may help in the reduction of vancomycin resistance and VRE colonization.

Optimization of antimicrobial therapy in vancomycin-resistant enterococcal bacteraemia using a rapid detection Gram-positive blood culture assay

Rapid molecular blood culture Gram-positive (BC-GP) assay can promptly identify vancomycin-resistant enterococcal (VRE) bloodstream infections (BSIs). We sought to evaluate patients with VRE BSI following the pre (N=44) and post (N=20) implementation of Verigene BC-GP assay. The average time to detection of VRE was 25.9±4.1h (95% confidence interval (CI): 17.6-34.1; P<0.001) earlier with Verigene BC-GP assay. Compared to patients in the pre-Verigene BC-GP period, the mean adjusted difference in time to administration of anti-VRE therapy was 18.2±7.8h (95% CI: 2.5-33.8; P=0.024) earlier among patients in the post-Verigene BC-GP period.

Daily Chlorhexidine Bathing in General Hospital Units – Results of the ABATE Infection Trial (Active BAThing to Eliminate Infection)

Daily Chlorhexidine Bathing in General Hospital Units – Results of the ABATE Infection Trial (Active BAThing to Eliminate Infection)

Antimicrobial resistance rates in gram-positive bacteria do not drive glycopeptides use.

Surveillance data are considered essential to appropriate empiric antibiotic therapy and stewardship. The objective of this study was to determine if a change in the rates of antibiotic resistance impacts antibiotic use in European hospitals. Glycopeptides use was selected to study the correlation between resistance rates and antibiotic use because of the restricted spectrum against resistant gram positive bacteria. PubMed, ECDC databases and national/regional surveillance systems were searched to identify glycopeptides´ consumption in defined daily dose per 1000 inhabitant-days (DID) and rate of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase negative staphylococci (MRCoNS), and vancomycin-resistant enterococci (VRE) in bloodstream infections (BSIs) in European countries between 1997 and 2015. Time trends were studied and associations between DID and BSI resistance rates were tested using multi-level mixed effect models. To account for the gap in the publication and dissemination of the yearly resistance data, a 2-year lag in the resistance rates was applied. Data on glycopeptides´ DID and resistance rates of target microorganisms in blood cultures were identified among 31 countries over a 19-year period. Glycopeptides use significantly increased (p<0·0001) while rates of MRSA BSIs decreased in majority of the countries (p<0·0001) and MRCoNS and VRE BSIs remained stable. Variation in glycopeptides’ DID was not associated with variation in BSIs due to MRSA (p = 0·136) and VRE (p = 0·613). After adjusting for MRCoNS and VRE resistance rates, among 21 countries, 11 (52%) had a concordant and 10 (48%) a discordant trend in yearly glycopeptides´ DID and MRSA BSI rates. No correlation was found between resistance rates and DID data even among 8 countries with more than 5% decrease in MRSA rates over time. (RC -0·009, p = 0·059). Resistance rate of MRSA, MRCoNS, and VRE BSIs does not impact DID of glycopeptides in European hospitals. This finding is key to redefining the role and structure of antimicrobial surveillance and stewardship programmes.

Secular Trends in Nosocomial Vancomycin-Resistant Enterococcal Bloodstream Infections Among United States Veterans Affairs Hospitals, Fiscal Years 2004 through 2014.

Secular Trends in Nosocomial Vancomycin-Resistant Enterococcal Bloodstream Infections Among United States Veterans Affairs Hospitals, Fiscal Years 2004 through 2014.

Comparison of Daptomycin and Linezolid in the Treatment of Vancomycin-Resistant Enterococcus faecium in the Absence of Endocarditis

Background Although linezolid and daptomycin are frequently used for the management of vancomycin-resistant Enterococcus (VRE) bloodstream infection, optimal treatment is undefined. Methods We conducted a retrospective cohort study from January 2010 to December 2013 of patients with VRE faecium (VREF) bloodstream infection in the absence of endocarditis treated with daptomycin or linezolid at a single 802-bed teaching hospital in Detroit, Mich. Ninety-day all-cause mortality, length of stay, bacteremia duration, antibiotic duration, and recurrence at 30 days were evaluated. Multivariable analysis was performed to determine the effect of treatment selection on mortality. Results One hundred eighteen patients were included. Seventy-four patients received daptomycin and 44 linezolid. There was no significant difference in baseline characteristics between the 2 groups with the exception of nursing home residence (P = 0.007), intensive care unit admission (P = 0.049), receipt of chemotherapy (P = 0.013), and neutropenia (P = 0.007). Ninety-day all-cause mortality was 46% and 27% (odds ratio = 2.27; 95% confidence interval, 1.1–5.07; P = 0.044) and mean bacteremia duration was 3.6 and 2.6 days (odds ratio = 2.52; 95% confidence interval, 1.17–5.42; P = 0.037) for daptomycin and linezolid, respectively. There was no significant difference in mean length of stay, mean antibiotic duration, and recurrence between the 2 groups. Moreover, there were no significant differences in mortality between the 2 groups after controlling for variables such as chemotherapy, neutropenia, and renal replacement therapy that were associated with increased mortality. Conclusions Our study showed that there was no significant difference in mortality between linezolid and daptomycin for therapy of VRE bacteremia in the absence of endocarditis after controlling for other variables that were associated with increased mortality.

Higher Doses of Daptomycin for Vancomycin-Resistant Enterococcal Bacteremia

Vancomycin-resistant enterococcal (VRE) bloodstream infections present treatment challenges. Studies have suggested that outcomes are improved with

Prediction of Bloodstream Infection Due to Vancomycin-Resistant Enterococcus in Patients Undergoing Leukemia Induction or Hematopoietic Stem-Cell Transplantation.

Bloodstream infection (BSI) to due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge. A single-center cohort representing 664 admissions for induction or hematopoietic stem-cell transplant (HSCT) from 2006 to 2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the model's predictive performance by calculating it for each of 16232 BSI at-risk inpatient days. VRE BSI incidence was 6.5% of admissions (2.7 VRE BSI per 1000 BSI at-risk days). Adjusted 1-year mortality and length of stay were significantly higher in patients with VRE BSI. VRE colonization (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI] = 3.4-20.6; P < .0001), renal insufficiency (aOR = 2.4; 95% CI = 1.0-5.8; P = .046), aminoglycoside use (aOR = 4.7; 95% CI = 2.2-9.8; P < .0001), and antianaerobic antibiotic use (aOR = 2.8; 95% CI = 1.3-5.8; P = .007) correlated most closely with VRE BSI. A prediction model with optimal performance included these factors plus gastrointestinal disturbance, severe neutropenia, and prior beta-lactam antibiotic use. The score effectively risk-stratified patients (area under the receiver operating curve = 0.84; 95% CI = 0.79-0.89). At a threshold of ≥5 points, per day probability of VRE BSI was increased nearly 4-fold. This novel predictive score is based on risk factors reflecting a plausible pathophysiological model for VRE BSI in patients with hematological malignancy. Integrating VRE colonization status with risk factors for developing BSI is a promising method of guiding rational use of empiric anti-VRE antimicrobial therapy in patients with hematological malignancy. Validation of this novel predictive score is needed to confirm clinical utility.

Risk Factors and Outcomes of Vancomycin-Resistant vs. Vancomycin-Sensitive Enterococcal Blood Stream Infections in Patients with Acute Myeloid Leukemia

BackgroundEnterococci are commensal of the gastrointestinal tract known to cause blood stream infections (BSIs). Studies have shown increased mortality from enterococcal BSI in neutropenic patients, indicating Vancomycin-resistant Enterococcal (VRE) infections causing increased mortality. Whether these differences in mortality apply to AML patients is unknown. The objectives of this study are to compare the risk factors and outcomes between VRE & VSE BSIs in AML patients.MethodsWe conducted a single center, retrospective cohort study of patients with enterococcal BSIs at H. Lee Moffitt Cancer Center from July 2011 to October 2015. Records were searched to identify AML patients with enterococcal BSI. Enterococcal species, neutropenia duration, Vancomycin exposure, VRE colonization, 7 and 30 day mortality, age, sex, length of stay, stem cell transplant & central line status were compared. We conducted statistical tests and Kaplan-Meier plot to analyze mortality trends.ResultsThere were a total of 77 AML patients with enterococcal BSI. Forty-two (54.5%) were caused by VRE. E. faecalis and E. faecium accounted for 28.5% and 62.3% of BSI respectively. The E. faecalis isolates were more likely to be VSE (83% vs. 8.3 %, P < 0.001) and E. fecium isolates to be VRE (71% vs. 29%, P < 0.001). Duration of neutropenia was significantly longer (27.3 vs. 20.7 days, P < 0.005) among AML patients with VRE BSI. Recent Vancomycin use and VRE colonization were significantly associated with VRE BSI. There were no significant differences in duration of bacteremia, length of stay and 7 and 30-day mortality between VRE vs. VSE BSI.Conclusion Enterococcal infections among AML patients are significantly more likely to be caused by Vancomycin-resistant E. faecium. The risk is increased by VRE colonization and Vancomycin exposure. The absence of statistical difference in 7 or 30-day mortality between VRE and VSE enterococcal BSI in our AML patients could indicate that in a homogenous group of patients, host and treatment-related factors may influence mortality more than species or susceptibility of the isolates. Our finding confirms VRE colonization as risk factor of VRE BSI for AML patients. This finding is important for future patient education and development of preventive and treatment protocols.Disclosures All authors: No reported disclosures.

Retrospective Study of Linezolid vs. Daptomycin for the Treatment of Vancomycin--resistant Enterococcal Bloodstream Infection

BackgroundDue to acquired resistance with Enterococcus, antibiotic therapy for vancomycin-resistant enterococcal (VRE) bloodstream infections (BSI) is limited. Current recommendations for the treatment of VRE BSI include either linezolid or daptomycin. The objective of this study was to compare clinical outcomes of VRE BSI in patients treated with linezolid or daptomycin.MethodsThis was a retrospective cohort study of inpatients from January 2010 to August 2016 conducted at a large academic medical center. Charts for review were selected based on data from the microbiology laboratory. Adult patients (≥ 18 years old) with VRE BSI treated with linezolid or daptomycin for at least 48 hours were included. Patients treated with linezolid and daptomycin combination therapy or any other antimicrobial agents were excluded. The primary outcome measure was 14-day in-hospital mortality. Secondary outcomes included time to blood culture clearance, microbiologic failure, antibiotic failure, and BSI relapse. A multivariable logistic regression model was performed to adjust for potential confounders.ResultsThere were a total of 93 patients, 62 treated with linezolid and 31 with daptomycin. Median daptomycin dose was 6.14 mg/kg (IQR, 5.98-6.71). Outcome of 14-day in-hospital mortality was not significantly different for patients treated with linezolid and daptomycin (17.7% vs. 29%, P = 0.21, respectively). Median time to blood culture clearance was not significantly different for linezolid vs. daptomycin therapy (3.0 days vs. 3.7 days, P = 0.78, respectively). All other secondary outcomes were not significantly different between treatment groups. Multivariate logistic regression analysis indicated 14-day in-hospital mortality was independently associated with Pitt bacteremia score (adjusted OR 1.48, 95% CI: 1.12-1.97) but showed no significant association with daptomycin treatment (adjusted OR 1.54, 95% CI: 0.46-5.14).ConclusionThere were no significant differences in clinical outcomes for patients treated with linezolid or daptomycin for the treatment of VRE BSI. Additional prospective studies with larger sample sizes are needed to further validate these conclusions. Role of daptomycin dose on outcomes requires further study.Disclosures All authors: No reported disclosures.

The Clinical Impact of Daptomycin Non-susceptible Enterococcus Bacteremia in Hematologic Malignancy

BackgroundPatients with hematologic malignancies are prone to colonization and infection with vancomycin-resistant Enterococcus (VRE), and VRE blood stream infections (BSI) in this population have been associated with a 30-day all-cause mortality approaching 40%. Daptomycin nonsusceptible Enterococci(DNSE) are on the rise, with institutional rates as high as 15%. The objective of this study was to determine the attributable mortality associated with resistance to daptomycin among VRE isolates.MethodsWe performed a retrospective cohort study of hematologic malignancy patients who developed either DNSE or daptomycin-susceptible VRE bacteremia between January 1, 2008 and December 31, 2016. Categorical variables were analyzed with chi-square or Fisher’s exact test and continuous variables were analyzed with a t-test or Wilcoxon rank sums test when appropriate. A p-value <0.05 was considered significant.Results34 cases of DNSE and 65 cases of VRE were identified. There were no significant differences noted in demographic data. At time of bacteremia, both DNSE and VRE cohorts had similar APACHE II scores (medians for DNSE and VRE were 19). The DNSE cohort had longer periods of neutropenia prior to the diagnosis of bacteremia [median 32.1 days vs.. 19.3 days, OR 1.85 95% CI (0.75-1.60)]. Patients with DNSE had a longer time to initiation of appropriate antibiotics (median 3.5 days vs. 2.0 days, P = 0.01). There were similar rates of bone marrow transplantation (53 % of DNSE vs. 51% of VRE), however, DNSE cases were more likely to develop graft vs. host disease [OR 3.6 95% CI (1.07-12.38)]. In the 90-day period prior to bacteremia, daptomycin exposure occurred in only 12 (35.3%) of DNSE cases vs.. 1 (1.5%) VRE case [OR 34.9 95% CI (4.3-284.1)]. Median lengths of stay (LOS) were similarly high in both groups, however, DNSE patients were more likely to have a LOS over 50 days as compared with VRE (P = 0.048). 30-day mortality in the DNSE cohort was 50% compared with 38% in the VRE group (P = 0.12).ConclusionIn a retrospective study, the 30-day mortality associated with DNSE bacteremia was 50%. Infection prevention interventions targeting this particular multi-drug-resistant organism are warranted in this vulnerable population.Disclosures All authors: No reported disclosures.

Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients.

Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are associated with significant mortality. Daptomycin exhibits concentration-dependent activity vs VRE in vitro, yet the clinical impact of higher-dose strategies remains unclear. We performed a national retrospective cohort study of hospitalized Veterans Affairs patients treated with standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin for VRE-BSI. Patient-related, microbiological, and outcomes data were abstracted from clinical databases. The primary outcome was overall survival, evaluated by Cox regression. Secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation. A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose (hazard ratio [HR], 2.68; 95% confidence interval; [CI], 1.33-3.06; P = .002) and medium-dose (HR, 2.66; 95% CI, 1.33-3.92; P = .003) daptomycin were associated with poorer survival. After adjusting for confounders, the relationship between poorer survival and standard-dose (adjusted HR [aHR], 2.58; 95% CI, 1.27-4.88; P = .004) and medium-dose (aHR, 2.52; 95% CI, 1.27-5.00; P = .008) daptomycin persisted. Thirty-day mortality was significantly lower among high-dose daptomycin-treated patients compared with other dosing strategies (risk ratio, 0.83; 95% CI, .74-.94; P = .015). Compared with standard-dose daptomycin, both medium-dose (HR, 0.78; 95% CI, .55-.90; P = .012) and high-dose daptomycin (HR, 0.70; 95% CI, .41-.84; P = .006) were associated with significantly improved microbiological clearance. No difference in the risk of CPK elevation was observed between the treatment groups (P = .504). High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.

Oral Vancomycin Is Highly Effective in Preventing Clostridium Difficile infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Introduction: Infection remains a leading cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (alloHCT). Among the most common infectious complications in alloHCT recipients is Clostridium difficile infection (CDI), a healthcare-associated, toxin-mediated diarrheal disease occurring in up to 30% of alloHCT recipients. We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients.Methods: We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin compared to no prophylaxis in 105 consecutive adults undergoing alloHCT at the University of Pennsylvania between April 2015 and July 2016. We initiated a pilot program of CDI prophylaxis with oral vancomycin for all alloHCT recipients starting in December 2015 (N=50). Patients received oral vancomycin 125 mg twice daily starting on the day of inpatient admission for alloHCT and continued until day of discharge. Prior to the initiation of this pilot, pharmacologic prophylaxis for CDI was not administered (control arm; N=55). Testing for C. difficile in patients with diarrhea was performed using an immunoassay for glutamate dehydrogenase and toxins A and B. Indeterminate results were confirmed by a molecular assay. Control and intervention patients were characterized by potential risk factors for CDI, including demographics, prior CDI, and recent broad-spectrum antibiotic use. Continuous variables were compared using the Wilcoxon rank-sum test, and categorical variables were compared using the χ2 or Fisher exact test. The primary outcome of interest was the incidence of CDI from inpatient admission for alloHCT to discharge.Results: The rate of recent broad-spectrum antibiotic use was significantly greater in the patients that received oral vancomycin prophylaxis compared to control patients (84.0% vs. 67.2; P=0.047). In addition, more patients in the vancomycin prophylaxis group received myeloablative conditioning (62.0% vs. 45.4%; P=0.09). There were no other significant differences in patient and transplant characteristics between the intervention and control groups, including mean age (54.3 vs. 56.4 years; P=0.6), myeloid malignancy (80.0% vs. 81.8%; P=0.8) and history of CDI in the prior year (22.0% vs. 9.0%; P=0.1). There were no cases of CDI in patients that received oral vancomycin prophylaxis (0/50; 0%) whereas 11/55 (20%) patients who did not receive vancomycin prophylaxis developed CDI during alloHCT (P=<0.001). The median (interquartile range) time to CDI diagnosis was 8 days (6 - 12). The median length of stay was non-significantly longer in the intervention patients (33.5 vs. 28.0 days; P=0.06), possibly due to the higher number of myeloablative conditioning transplants in the prophylactic vancomycin group. There were no cases of vancomycin-resistant enterococcus bloodstream infection in patients who received vancomycin prophylaxis.Conclusion: Prophylactic vancomycin is highly effective in preventing CDI in alloHCT recipients. Since CDI and/or its treatment may alter the gut microbiome, longer follow up will determine if there is any impact on other outcomes. Six month follow-up data for graft-versus-host disease and overall survival will be presented. DisclosuresFrey:Novartis: Research Funding; Amgen: Consultancy; Servier: Consultancy. Gill:Novartis: Patents & Royalties, Research Funding. Hexner:Novartis: Research Funding; Blueprint medicines: Consultancy. Mangan:Incyte: Other: Advisory Board; Novartis: Research Funding. Porter:Novartis: Patents & Royalties, Research Funding; Genentech: Employment.

Advances in prevention and treatment of vancomycin-resistant Enterococcus infection.

This article reviews data, particularly from the last 2 years, addressing the prevention and treatment of vancomycin-resistant Enterococcus (VRE). We focus on infection control, particularly active screening, use of contact precautions as well as pharmacologic options for therapy. This is timely given the evolving priorities in efforts towards the prevention and treatment of multidrug-resistant organisms globally. Key findings include new data regarding the impact of contact precautions on the incidence of VRE colonization and bloodstream infection, new laboratory screening methods, and novel decolonization strategies and treatments. Additional and specific measures beyond standard precautions for infection prevention of VRE remain controversial. Horizontal measures such as chlorhexidine bathing appear beneficial, as are nontouch environmental cleaning methods. Treatment options for invasive disease have improved considerably in the last decade. Decolonization strategies require further research. Overall, the threat of VRE seems exaggerated.

Vancomycin-resistant Enterococcus colonization and bloodstream infection: prevalence, risk factors, and the impact on early outcomes after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia.

Screening for vancomycin-resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting. Consecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient. Of a total of 203 patients (median age 54years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100days, and 107 (53%) remained non-colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre-transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60years, HCT-comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100days post HCT. VRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post-HCT survival.

Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L

PurposeCase reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. MethodsWe performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. FindingsForty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). ImplicationsDuration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.

Daptomycin versus linezolid for the treatment of vancomycin-resistant enterococcal bacteraemia: implications of daptomycin dose

Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21–0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6–9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17–0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09–0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45–4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia.

Emergence of vancomycin-resistant Enterococcus at a tertiary paediatric hospital in South Africa

During 2013, the haematology/oncology unit at a tertiary level paediatric hospital in South Africa experienced the emergence of infection with vancomycin-resistant Enterococcus (VRE). To describe the clinical and molecular aspects of the cases identified. VRE isolates identified from blood culture specimens processed at the National Health Laboratory Service were screened for the presence of the vancomycin resistance genes vanA, B and C1, 2 and 3. Further characterisation of these isolates was carried out using pulsed-field gel electrophoresis (PGFE) and multilocus sequence typing (MLST). Clinical records of infected patients were reviewed to identify possible risk factors, while surveillance with rectal swabs was performed to identify VRE-colonised patients. Four patients with haematological malignancies were identified with VRE bloodstream infections. Patients were immunocompromised at the time of the bloodstream infection (BSI), with receipt of vancomycin prior to VRE-BSI, and infections were treated with linezolid. Colonisation with VRE was found in 8 of 55 patients screened. Infected and colonised patients were isolated in the unit during their admission and strict contact precaution infection control practices were instituted. The vanA gene was identified in all of the isolates but one. PFGE and MLST results showed a degree of genetic relatedness between certain isolates obtained from rectal swab and blood culture samples, suggesting possible patient-to-patient transmission or persistence of the isolates in the unit. Strict infection control practices are necessary to prevent infection and transmission of resistant organisms among vulnerable patients.