Vancomycin-resistant Enterococci Bloodstream Infections Research Articles

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

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

Clinical epidemiology of vancomycin-resistant Enterococcus gallinarum and Enterococcus casseliflavus bloodstream infections.

This study aimed to evaluate the clinical outcomes of vancomycin-resistant enterococcal bloodstream infections (VRE BSI) caused by Enterococcus gallinarum or Enterococcus casseliflavus. Variables associated with treatment failure were determined and treatment options were compared. This was a national retrospective study of hospitalised Veterans Affairs patients with non-faecium, non-faecalis VRE BSI. The primary outcome was treatment failure, defined as a composite of: (i) 30-day all-cause mortality; (ii) microbiological failure; and (iii) 30-day VRE BSI recurrence. Stepwise Poisson regression was conducted to determine variables associated with treatment failure. In total, 48 patients were included, with 29 cases (60.4%) caused by E. gallinarum and 19 cases (39.6%) caused by E. casseliflavus. Among these cases, 20 (41.7%) were treated with an anti-VRE agent (linezolid or daptomycin) and 28 (58.3%) were treated with an anti-enterococcal β-lactam. Overall, 30-day mortality was 10.4% (5/48) and composite treatment failure was 39.6% (19/48). In multivariate analysis, treatment with an anti-enterococcal β-lactam was associated with increased treatment failure in comparison with anti-VRE therapy (adjusted risk ratio = 1.73, 95% confidence interval 1.06-4.97; P = 0.031). Overall, treatment with linezolid or daptomycin for vancomycin-resistant E. gallinarum or E. casseliflavus BSI resulted in improved clinical outcomes in comparison with anti-enterococcal β-lactam treatment.

Patient-level analysis of incident vancomycin-resistant enterococci colonization and antibiotic days of therapy.

Vancomycin-resistant enterococci (VRE) infections are a public health threat associated with increased patient mortality and healthcare costs. Antibiotic usage, particularly cephalosporins, has been associated with VRE colonization and VRE bloodstream infections (VRE BSI). We examined the relationship between antimicrobial usage and incident VRE colonization at the individual patient level. Prospective, weekly surveillance was undertaken for incident VRE colonization defined by negative admission but positive surveillance swab in a medical intensive care unit over a 17-month period. Antimicrobial exposure was quantified as days of therapy (DOT)/1000 patient-days. Multiple logistic regression was used to analyse incident VRE colonization and antibiotic DOT, controlling for demographic and clinical covariates. Ninety-six percent (1398/1454) of admissions were swabbed within 24 h of intensive care unit (ICU) arrival and of the 380 patients in the ICU long enough for weekly surveillance, 83 (22%) developed incident VRE colonization. Incident colonization was associated in bivariate analysis with male gender, more previous hospital admissions, longer previous hospital stay, and use of cefepime/ceftazidime, fluconazole, azithromycin, and metronidazole (P < 0·05). After controlling for demographic and clinical covariates, metronidazole was the only antibiotic independently associated with incident VRE colonization (odds ratio 2·0, 95% confidence interval 1·2-3·3, P < 0·009). Our findings suggest that risk of incident VRE colonization differs between individual antibiotic agents and support the possibility that antimicrobial stewardship may impact VRE colonization and infection.

The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation.

Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.

Epidemiology and molecular typing of VRE bloodstream isolates in an Irish tertiary care hospital.

Ireland has the highest rate of vancomycin-resistant Enterococcus faecium (VREfm) isolated from blood of nosocomial patients in Europe, which rose from 33% (110/330) in 2007 to 45% (178/392) in 2012. No other European country had a VREfm rate from blood cultures of >25%. Our aim was to elucidate the reasons for this significantly higher rate in Ireland. The epidemiology and molecular typing of VRE from bloodstream infections (BSIs) was examined in a tertiary care referral hospital and isolates were compared with those from other tertiary care referral centres in the region. The most common source of VRE BSIs was intra-abdominal sepsis, followed by line-related infection and febrile neutropenia. Most of the isolates were positive for vanA; 52% (43/83) possessed the esp gene and 12% (10/83) possessed the hyl gene. Genotyping by SmaI macrorestriction analysis (PFGE) of isolates revealed clonal relatedness between bloodstream isolates and environmental isolates. VRE BSI isolates from two other tertiary care hospitals in the Dublin region showed relatedness by PFGE analysis. MLST revealed four STs (ST17, ST18, ST78 and ST203), all belonging to the clonal complex of hospital-associated strains. Irish VRE BSI isolates have virulence factor profiles as previously reported from Europe. Typing analysis shows the spread of individual clones within the hospital and between regional tertiary care hospitals. Apart from transmission of VRE within the hospital and transfer of colonized patients between Irish hospitals, no other explanation for the persistently high VREfm BSI rate in Ireland has been found.

Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant Enterococcus spp

We conducted a retrospective study on the impact of the empiric use of linezolid on mortality in vancomycin-resistant Enterococcus spp (VRE)-colonized hematology and hematopoietic stem cell transplantation (HSCT) patients. VRE-colonized inpatients for whom complete data were available (n=100) were divided into two groups: those who received empiric linezolid in the course of fever refractory to broad-spectrum antibiotics, replacing the glycopeptide utilized for the previous 48 h, and those who did not (control group). All patients were followed until hospital discharge or death. The impact of linezolid and risk factors for all-cause mortality were evaluated; variables with p<0.10 were analyzed in a multivariate model. A Kaplan-Meier survival analysis was done to compare survival among febrile patients colonized by VRE who received empiric linezolid with patients who did not receive linezolid. Patients empirically prescribed linezolid were generally younger (median age 33 vs. 44 years; p=0.008) and more likely to be recipients of an allogeneic HSCT (24 (68.6%) vs. 24 (36.9%); p=0.009) than patients who did not receive the drug. Fourteen (21.5%) VRE bloodstream infections were diagnosed, all in patients who did not receive empiric linezolid (p=0.002). In-hospital mortality was comparable in empiric linezolid and non-linezolid users (19 (54.3%) vs. 27 (41.5%), respectively; p=0.293). The Kaplan-Meier survival analysis showed no significant difference in survival comparing the group that received linezolid to the group that did not (p=0.72). Graft-versus-host disease (GVHD; odds ratio (OR) 5.90, 95% confidence interval (CI) 1.46-23.79; p=0.012) and persistence of neutropenia (OR 6.93, 95% CI 1.72-27.94; p=0.0065) were independent predictors of all-cause in-hospital death in HSCT patients, and persistence of neutropenia in non-HSCT patients (OR 8.12, 95% CI 1.22-53.8; p=0.030). The empiric use of linezolid in VRE-colonized hematology patients had no impact on mortality, which appeared rather to be associated with the persistence of neutropenia in general and GVHD in the HSCT group.

Frequency, Risk Factors, and Outcomes of Vancomycin-Resistant Enterococcus Colonization and Infection in Patients with Newly Diagnosed Acute Leukemia: Different Patterns in Patients with Acute Myelogenous and Acute Lymphoblastic Leukemia

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

Optimizing therapy for vancomycin-resistant enterococcal bacteremia in children.

Uncertainties exist regarding the optimal treatment for vancomycin-resistant enterococcal (VRE) bloodstream infections, particularly in settings in which ampicillin cannot be used. Quinupristin-dalfopristin, linezolid, and daptomycin, all approved between 1999 and 2003, represent the mainstays of therapy for VRE bacteremia, although only linezolid has been specifically approved by the United States Food and Drug Administration for this indication. The main objective of this review is to compare the relative efficacies, dosing strategies, and side-effect profiles of quinupristin-dalfopristin, linezolid, and daptomycin for VRE bacteremia in the pediatric population. A brief description of recently approved broad-spectrum Gram-positive agents that may have a role in the management of VRE bacteremia in upcoming years is also provided. Linezolid, despite its bacteriostatic activity against VRE, may be the most versatile of the available drugs. It has activity against both Enterococcus faecalis and E. faecium, can be administered orally, and resistance appears to be less of a concern with linezolid compared with the other agents. Additionally, the results of two recent meta-analyses demonstrate more favorable outcomes with linezolid compared with daptomycin for the treatment of VRE bacteremia. The clinical pharmacokinetics of linezolid have been well described in children. The most notable concern with linezolid, however, is toxicities associated with prolonged use. Until more prospective data are available, we favor linezolid as first-line therapy for the treatment of VRE bacteremia in children.

Vancomycin-resistant enterococcal bacteremia pharmacotherapy.

To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE). A MEDLINE literature search was performed for the period 1946 to May 2014 using the search terms Enterococcus, enterococci, vancomycin-resistant, VRE, bacteremia, and bloodstream infection. References were also identified from selected review articles. English-language case series, cohort studies, and meta-analyses assessing the options in the pharmacotherapy of VRE BSIs in adult patients were evaluated. Studies were identified that utilized linezolid, quinupristin/dalfopristin (Q/D), and daptomycin. In all, 8 comparative retrospective cohort studies, 2 meta-analyses of daptomycin and linezolid, and 3 retrospective comparisons of linezolid and Q/D were included for review. Mortality associated with VRE BSIs was high across studies, and the ability to determine differences in outcomes between agents was confounded by the complex nature of the patients included. Two meta-analyses comparing daptomycin with linezolid for VRE BSIs found modest advantages for linezolid, but these conclusions may be hampered by heterogeneity within the included studies. VRE BSIs remain a difficult-to-treat clinical situation. Differences in toxicity between the agents used to treat it are clear, but therapeutic differences are more difficult to discern. Meta-analyses suggest that a moderate advantage for linezolid over daptomycin may exist, but problems with the nature of studies that they included make definitive conclusions difficult.

Therapeutic Options for Resistant Gram Positives

Vancomycin remains the current gold standard for treatment of serious MRSA (methicillin resistant Staphylococcus aureus) infections despite uncertainties about rates of toxicity and the optimal dosing strategy. The only alternative for bloodstream infections (BSI) based on prospective randomised controlled trial data is daptomycin. However, higher doses should be implemented to prevent resistance emerging. Although linezolid and ceftaroline have been shown to be effective BSI treatment in retrospective cohort studies, there is no prospective randomised comparative data with vancomycin. These agents should thus be considered as salvage therapy options. In the treatment of MRSA cSSSIs (complicated skin and skin structure infections), daptomycin, linezolid, ceftaroline and telavancin have all been shown to be equally effective to vancomycin and thus the choice of agent is dependent on the side effect profile and patient setting. In the treatment of nosocomial MRSA pneumonia, both linezolid and telavancin have been shown to be non-inferior to vancomycin. Linezolid was shown to have improved microbiological and clinical cure rates compared with vancomycin, but with no mortality benefit in a randomised controlled trial by Wunderink et al., [1, 2]. Debate still exists, however, as to whether these studies, in the absence of a mortality benefit, provide sufficient evidence to recommend linezolid or telavancin above vancomycin in the treatment of MRSA pneumonia. For the treatment of VRE (Vancomycin Resistant Enterococci) BSI, prospective data is lacking and recommendations are based upon in vitro activity and cohort studies. Quinupristin-dalfopristin is limited by its side effect profile and the need for a central line. As such the first line agents include daptomycin and linezolid. Although two recent meta-analyses suggest improved outcomes with linezolid over daptomycin, this may reflect suboptimal daptomycin dosing rather than linezolid superiority. Tigecycline, although active against VRE, has been shown to be inferior in eradication rates compared with linezolid [3]. Combination therapy for MRSA or VRE infections cannot currently be endorsed and thus should be limited to settings where no other alternative is available.

Vancomycin-resistant enterococci infection: not just for the transplanted

Vancomycin-resistant enterococcal (VRE) blood stream infections (BSIs) pose significant hazards to patients with hematologic malignancy. We compared and examined VRE BSI rates, patient characteristics and clinical outcomes for two cohorts of patients: those who did and did not undergo hematopoietic cell transplant (HCT). In this single institution study, we retrospectively analyzed records of consecutive patients from 1998 through 2011. Over this 14-year period, VRE was identified in 14% of all BSIs in patients with HCT with a cumulative rate of 1.9% (48/2581 BSIs/patients). VRE was identified in 10% of all BSIs in non-HCT patients with a cumulative rate of 1.1% (35/3154 BSIs/patients). Transplant patients who developed VRE BSI tended to be younger, hospitalized more frequently, were exposed to vancomycin therapy frequently, and were more likely to have had a central venous catheter removed. VRE remains a significant cause of morbidity and mortality, as 22 deaths were directly or indirectly attributed to this infection. Both HCT and non-HCT patients are susceptible to VRE infection and are equally at risk for adverse outcomes related to VRE BSI.

Treatment considerations in vancomycin-resistant enterococcal bacteremia: daptomycin or linezolid? A review

Vancomycin resistant enterococcal bloodstream infections are an important cause of morbidity and mortality in hospitalized patients. A search of the literature was undertaken to determine the optimal antimicrobial therapy for the management of vancomycin resistant enterococcal bloodstream infections. MEDLINE, EMBASE, and the Cochrane Library (unrestricted to time or language) were searched for studies of vancomycin resistant enterococcal bloodstream infections in adults reporting outcomes of direct comparisons of linezolid versus daptomycin on November 26, 2012. Studies of basic science, reviews, commentaries, pharmacologic, epidemiologic, or pediatric studies, and those studies examining conditions other than enterococcal bacteremia, a single antimicrobial agent or other antimicrobials were excluded. 226 studies were screened for eligibility and yielded eight studies evaluating a total of 807 patients. Inter-rater agreement was 100 %. Qualitative evaluation of the studies was performed using the Newcastle-Ottawa scale. No randomized controlled trials were identified. All studies were retrospective cohorts and non-randomized. 458 (57 %) patients treated with linezolid and 349 (43 %) with daptomycin were analyzed. Variable comorbidities and severity of illness were described in the included studies and reported here for comparison. The optimal treatment of vancomycin resistant enterococcal bloodstream infections is yet to be determined. Well-designed prospective studies are needed to lend more convincing evidence regarding choice of antimicrobial therapy for this important multidrug resistant organism.

Treatment of Vancomycin-Resistant Enterococcal Bacteremia in an Observational Cohort of Neutropenic Oncology Patients

Background Vancomycin-resistant Enterococcus (VRE) is an increasingly common nosocomial pathogen causing significant morbidity and mortality in patients with neutropenic cancer. We evaluated outcomes in an observed cohort of subjects with VRE bacteremia and compare the effectiveness of 2 antibiotics commonly used to treat VRE infections: daptomycin and linezolid. Methods Patients with neutropenic cancer with VRE blood stream infections treated with daptomycin or linezolid were identified through electronic medical record, and a retrospective chart review was conducted. Results Eighty-one patients were included. There were 49 men (60%) and 32 women; the mean age was 59.3 years. Mean white blood cell count at the time of blood stream infection was 0.3, and the median duration of bacteremia was 2 days (range, 1–25 days). Leukemia was the underlying diagnosis in 82.7%. Only 4 patients received anti-VRE therapy within 4 hours, 14 patients received VRE-specific therapy within 24 hours of first positive culture. The overall treatment failure rate was 35.8%; daptomycin, 41.4%; and linezolid, 21.7% (P = 0.13). Primary causes of treatment failure were persistent bacteremia and death. The 30-day mortality rate was 38.3%. Of these 31 deaths, 22.6% were directly attributable to VRE, with VRE being contributory in an additional 22.6%. Overall mortality in patients treated with daptomycin (39.7%) or linezolid (34.8%) did not differ (P = 0.80). Resistance to both agents was observed. Conclusions We found a 38.3% 30-day mortality rate, emphasizing the need for prevention and perhaps early inclusion of VRE-specific therapy for those with known colonization. Outcomes of culture-directed therapy with linezolid or daptomycin did not differ by antibiotic choice.

Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies

In patients with haematological or oncological malignancies, we aimed to assess the rate of intestinal colonisation and blood stream infections (BSI) with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and vancomycin-resistant enterococci (VRE), mortality and risk factors associated with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE in combination with adapted empiric treatment of febrile neutropenia. Within 72 h of admission to our department, an ESBLE and VRE screening stool sample was collected. In the case of neutropenic fever, blood cultures were drawn. Data of all admitted patients were prospectively documented. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for progression from intestinal colonisation to BSI. During the study period, 1,805 stool samples were obtained from 513 patients during 1,012 inpatient stays, and 2,766 blood cultures were obtained from 578 patients during 1,091 inpatient stays. Ninety (17.5 %) of these patients were colonised with ESBLE and 51 (9.9 %) with VRE. Proportions of 40 % (36/90) of ESBLE and 61 % (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6 %) ESBLE-colonised patients and 1/51 (2 %) VRE-colonised patients developed BSI with the respective organism. None of these patients died after receiving early appropriate empiric antibiotics based on colonisation status. Colonisation with ESBLE or VRE was associated with increased risk ratios (RR) towards developing ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89–7.04] and VRE BSI (RR 10.2, 95 % CI: 7.87–13.32), respectively. Acute myelogenous leukaemia and prior treatment with platinum analogues or quinolones were identified as independent risk factors for ESBLE BSI in colonised patients. Intestinal ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology patients in combination with directed empiric treatment may reduce ESBLE BSI-related mortality.

Evaluation of the Treatment of Vancomycin-Resistant Enterococcal Urinary Tract Infections in a Large Academic Medical Center

Vancomycin-resistant enterococci (VRE) are a common cause of nosocomial urinary tract infections (UTIs) among hospitalized patients. Clinicians need to differentiate between VRE-associated urinary colonization, asymptomatic bacteriuria, and UTIs to determine the need for treatment and length of therapy. To characterize the diagnosis and management of VRE from urinary sources, including compliance with institutional treatment guidelines, and identify risk factors associated with clinical failure. We performed a retrospective, single-center, cohort study among patients with VRE-positive cultures from urinary sources over a 3-year study period (July 2008-September 2011). Descriptive statistics were used to evaluate demographics, diagnostics, guideline compliance, pharmacotherapy, and outcomes. Risk factors associated with clinical failure were identified by multivariate logistic regression analysis. Two hundred sixty-nine distinct episodes of VRE met inclusion criteria among 252 patients. Forty-seven percent and 77% of episodes occurred in patients admitted to an intensive care unit and hospitalized for 7 or more days, respectively. Fifty-eight percent of the episodes were classified as asymptomatic bacteriuria or colonization. Compliance with institutional treatment guidelines for the appropriate drug, dose, and duration occurred in approximately 70% of the cases. Among noncompliant cases (n = 83), 48 (58%) were overtreated, and 35 (42%) were undertreated. Clinical failure among all cases was common, including mortality (17.1%). Factors independently associated with clinical failure determined on multivariate analysis included weight 100 kg or more (OR 5.30; 95% CI 1.42-12.21; p = 0.014), renal disease (OR 2.57; 95% CI 1.02-6.47; p = 0.048), indwelling catheter (OR 4.62; 95% CI 1.05-18.24; p = 0.046), and VRE bloodstream infection (OR 15.71; 95% CI 2.9-128.7; p < 0 .001). Improved education is needed to minimize cases of overtreatment and undertreatment of VRE-associated UTIs and decrease inappropriate drug-related costs and clinical failure rates. Risk factors for clinical failure can be used to risk stratify VRE-associated UTIs and further guide treatment decisions.

Polyclonal Outbreak of Vancomycin-resistant Enterococcus faecium in a Pediatric Oncology Department

We present a polyclonal outbreak of vancomycin-resistant enterococci (VRE) colonization in a pediatric oncology department and the role of a bundle of actions. After the occurrence of VRE bloodstream infections in 2 patients, an active surveillance of VRE colonization was started. Enhanced infection control measures and closure of the department to new admissions for the first 3 months were implemented. Among 32 patients screened for VRE, 21 were found colonized. Daily prevalence of VRE colonization among hospitalized patients ranged from 40% to 75%, but no new VRE infections occurred. Monthly incidence of VRE colonization decreased from 2.5 to 0.6 cases per 100 occupied bed-days at the end of this outbreak by the implementation of the above-mentioned measures. All VRE isolates tested were Enterococcus faecium carrying VanA gene. Pulsed field gel electrophoresis showed a polyclonal outbreak. A case-control study did not show any particular risk factors for colonization. High use of glycopeptide was noted before study outbreak that was drastically decreased during the study but only temporarily. Control of VRE in pediatric oncology departments with high colonization rates is challenging and requires a multifaceted strategy. Polyclonal spread of VRE found in this study suggests a possible effect of prior antimicrobial overuse and the critical need for antimicrobial stewardship especially in the era of multidrug-resistant bacteria.

Daptomycin Therapy for Vancomycin-Resistant Enterococcus Bacteremia in Neutropenic Patients With Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients

Background: Vancomycin-resistant Enterococcus fascium (VRE) are rapidly emerging nosocomial pathogens in the United States and worldwide. Vancomycin resistance is recognized to be an independent risk factor for increased morbidity and mortality among patients with enterococcal bloodstream infections (BSI); thus, early appropriate therapy is vital in improving outcomes. We report our experience in treating VRE BSI in patients with hematologic malignancies with daptomycin, a cyclic lipopeptide antibiotic with bactericidal activity against VRE. Methods: We performed retrospective chart review for patients with hematologic malignancies treated with daptomycin for a VRE BSI from January 2005 to May 2009. Patients were assessed for microbiological cure and survival. Patients were identified using a computerized clinical microbiology laboratory records. Results: Of 74 patients with a VRE BSI, 40 patients (31 male patients; median age, 61 years) met criteria and were included in the study. In this series, 35.6% of the patients had received a hematopoietic stem cell transplant, and 57.8% of the patients were neutropenic. Vancomycinresistant Enterococcus BSI occurred at a median of 20 days (4Y109 days) of neutropenia among these patients. The patients were treated with daptomycin monotherapy (62.5%) or daptomycin plus other antimicrobial(s) (37.5%). For those who were successfully treated with daptomycin alone, the median duration of therapy was 9 days (1Y36 days). Overall, 92.3% of the patients achieved a microbiological cure, which was evident at a median of 1 day (1Y16 days) after the initiation of therapy. Conclusion: Daptomycin is an effective agent for the treatment of VRE BSI. For both daptomycin monotherapy or combination therapy, we would recommend an intravenous dose of 8 mg/kg once daily for 10 to 14 days.

Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies

In patients with haematological or oncological malignancies, we aimed to assess the rate of intestinal colonisation and blood stream infections (BSI) with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and vancomycin-resistant enterococci (VRE), mortality and risk factors associated with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE in combination with adapted empiric treatment of febrile neutropenia. Within 72 h of admission to our department, an ESBLE and VRE screening stool sample was collected. In the case of neutropenic fever, blood cultures were drawn. Data of all admitted patients were prospectively documented. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for progression from intestinal colonisation to BSI. During the study period, 1,805 stool samples were obtained from 513 patients during 1,012 inpatient stays, and 2,766 blood cultures were obtained from 578 patients during 1,091 inpatient stays. Ninety (17.5 %) of these patients were colonised with ESBLE and 51 (9.9 %) with VRE. Proportions of 40 % (36/90) of ESBLE and 61 % (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6 %) ESBLE-colonised patients and 1/51 (2 %) VRE-colonised patients developed BSI with the respective organism. None of these patients died after receiving early appropriate empiric antibiotics based on colonisation status. Colonisation with ESBLE or VRE was associated with increased risk ratios (RR) towards developing ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89-7.04] and VRE BSI (RR 10.2, 95 % CI: 7.87-13.32), respectively. Acute myelogenous leukaemia and prior treatment with platinum analogues or quinolones were identified as independent risk factors for ESBLE BSI in colonised patients. Intestinal ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology patients in combination with directed empiric treatment may reduce ESBLE BSI-related mortality.

Emergence of vancomycin-resistant Enterococcus bloodstream infections in southern Taiwan

An increased incidence of vancomycin-resistant enterococcal bloodstream infections (VRE BSI) in the United States has been noted in recent years. There were a few reports of VRE BSI in Taiwan. This study is intended to show the epidemiology, clinical features and outcomes of VRE BSI at a medical center in southern Taiwan. A retrospective study was conducted from January 1, 2005 to December 31, 2010. All patients with VRE BSI episodes were identified and their medical records were reviewed. A total of 69 episodes of VRE BSI were identified in the study period. The incidence rate increased from 0.01 episodes of VRE BSI/1000 patient-days in 2005 to 0.07 episodes of VRE BSI/1000 patient-days in 2010. The 30-day mortality rate was 52.17% for all patients with VRE BSI. The mortality rate of patients who received invitro active and inactive antimicrobial therapy for VRE BSI was 40% and 100%, respectively (p<0.001). Factors associated with mortality were shock [odds ratio (OR) 24.4, 95% confidence interval (CI) 3.6-163.2, p=0.001], renal failure (OR 90.9, 95% CI 1.9-4404.3, p=0.02), and underlying liver cirrhosis (OR 12.4, 95% CI 1.2-125.8, p=0.03). Use of linezolid for VRE BSI showed a trend for lower 30-day mortality than daptomycin therapy (35.5% vs. 56.3%, p=0.17). VRE BSI is increasingly important in the study hospital and is associated with a significant mortality rate. Appropriateness of antimicrobial therapy has a prognostic impact on patients with VRE BSI.

Certification in infection control matters: Impact of infection control department characteristics and policies on rates of multidrug-resistant infections

The study objective is to describe infection control policies aimed at multidrug-resistant organisms (MDRO) in California hospitals and assess the relationship among these policies, structural characteristics, and rates of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) bloodstream infections and Clostridium difficile infections. Data on infection control policies, structural characteristics, and MDRO rates were collected through a 2010 survey of California infection control departments. Bivariate and multivariable Poisson and negative binomial regressions were conducted. One hundred eighty hospitals provided data (response rate, 54%). Targeted MRSA screening upon admission was reported by the majority of hospitals (87%). The majority of hospitals implemented contact precautions for confirmed MDRO and C difficile patients; presumptive isolation/contact precautions for patients with pending screens were less frequently implemented. Few infection control policies were associated with lower MDRO rates. Hospitals with a certified infection control director had significantly lower rates of MRSA bloodstream infections (P < .05). Although most California hospitals are involved in activities to decrease MDRO, there is variation in specific activities utilized with the most focus placed on MRSA. This study highlights the importance of certification and its significant impact on infection rates. Additional research is needed to confirm these findings.