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Vancomycin-Resistant Enterococcal Bloodstream Infections on a Hematopoietic Stem Cell Transplant Unit: Are the Sickgetting Sicker?

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Vancomycin-Resistant Enterococcal Bloodstream Infections on a Hematopoietic Stem Cell Transplant Unit: Are the Sickgetting Sicker? Bone Marrow Transplantation (2006) 38, 813–819 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt ORIGINAL ARTICLE Vancomycin-resistant enterococcal bloodstream infections on a hematopoietic stem cell transplant unit: are the sickgetting sicker? ER Dubberke1,2, JM Hollands3, P Georgantopoulos2, K Augustin3, JF DiPersio1,4, LM Mundy5,6 and HJ Khoury1,4 1Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 2Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA; 3Barnes-Jewish Hospital, St Louis, MO, USA; 4Division of Oncology, Section Leukemia and Bone Marrow Transplantation, Washington University School of Medicine, St Louis, MO, USA; 5School of Public Health, St Louis University, St Louis, MO, USA and 6The Jonathan Lax Treatment Center, Philadelphia, PA, USA Patients with hematologic malignancies and hemato- Introduction poietic stem cell transplant (HSCT) recipients are at high riskfor bacterial bloodstream infections (BSI) owing to Patients with hematologic malignancies and hematopoietic resistant organisms. Data describing the outcomes of stem cell transplant (HSCT) recipients are at high risk for vancomycin-resistant enterococcal (VRE) BSI in this bloodstream infections (BSI) that arise from organisms that patient population are limited. We performed a retro- normally colonize the human intestine.1–4 Because of their spective cohort study of all cases of VRE BSI that occured high severity of underlying illness, prolonged hospitaliza- between February 1996 and December 2002 on the tion and frequent broad-spectrum antibiotic exposures, Leukemia/HSCT unit at Barnes-Jewish Hospital. There these patients are commonly colonized with resistant were 68 episodes of VRE BSI in 60 patients with acute organisms and therefore at high risk for BSI owing to (53%) or chronic (8%) leukemia, non-Hodgkin’s lym- resistant organisms.1,2 This is important because infections phoma (22%) or other malignant hematologic disorders owing to resistant organisms are associated with increased (17%). A total of 13, 32 and 32% were recipients of morbidity, costs and mortality.5 autologous, related and matched-unrelated transplants, Enterococci are normal inhabitants of the human colon respectively. Forty-two of allograft recipients had active and are the third most frequent cause of health-care- acute graft-versus-host disease (GVHD) and 32% chronic associated infections in the United States.6–8 Up to 73% of GVHD. Only 57% were neutropenic, 52% had refrac- enterococcal BSIs are due to vancomycin-resistant strains.9 tory/relapsed malignancy and 60% had end organ Risk factors for vancomycin-resistant enterococcal (VRE) dysfunction with a median APACHE II score of 17. colonization and infection include prolonged hospitaliza- Median survival after VRE BSI was 19 days. Pneumonia, tion, intensive care unit (ICU) stay, advanced age, receipt of anti-fungal drugs and low APACHE II score at immunocompromised state, neutropenia, high severity of the time of the VRE BSI remained significant riskfactors underlying illness, antibiotic exposure, and indwelling for death on multivariable analysis. Our analysis suggests urinary and vascular catheters,8,10–13 characteristics com- that in patients with hematological malignancies or monly found in patients on HSCT units. Several studies HSCT, VRE may not have the behavior of a virulent have investigated the significance of VRE infections in pathogen. VRE BSI may simply be a marker of these different patient populations and controversy exists as to patients’ already existing critical medical condition. whether VRE infections are associated with worse out- Bone Marrow Transplantation (2006) 38, 813–819. comes compared to vancomycin-sensitive enterococci.14–21 doi:10.1038/sj.bmt.1705530; published online 23 October 2006 Although some studies have indicated VRE infections are Keywords: vancomycin-resistant enterococcus; blood- associated with worse outcomes in immunocompromised stream infection; transplantation; leukemia; mortality patients,19,20 data on VRE infections in patients with hematologic malignancies and HSCT recipients are limited.21,22 Therefore we conducted a retrospective cohort study to determine the patient characteristics associated with VRE BSI and risk factors for death in these patients. Correspondence: Dr ER Dubberke, Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, 660 S Euclid, Box 8051, St Louis, MO 63110, USA. Patients and methods E-mail: [email protected] Preliminary data was presented in part at the 2006 BMT Tandem Meetings, Honolulu, HI. Study design Received 20 April 2006; revised 10 July 2006; accepted 18 August 2006; All cases of VRE BSI occurring between February 1996 published online 23 October 2006 and December 2002 on the HSCT unit at Barnes-Jewish VRE bloodstream infections on an HSCT unit ER Dubberke et al 814 Hospital were prospectively identified by the Infection qualitative PCR or culture from the blood or a quantitative Control Department. Barnes-Jewish Hospital is a 1251-bed PCRX10 000 copies/ml. CMV pneumonia was defined tertiary care facility located in St Louis, MO and is as the presence of histopathological evidence of CMV affiliated with Washington University School of Medicine. pneumonia or a positive culture by bronchoalveolar lavage The HSCT unit has 27 positive pressure, high efficiency in a patient with radiographic evidence of pneumonia. particulate air-filtered, single-occupancy rooms and can GVHD was diagnosed and graded according to standard accommodate up to six patients requiring ICU care. All definitions.25,26 Mortality attributable to VRE BSI was patients with acute leukemia and HSCT recipients are defined as a patient who had an acute clinical deterioration admitted to this unit. Nine hundred and sixty-eight temporally associated with the VRE BSI culminating in autologous and 612 allogeneic transplants were performed death. during the study period. Although there was no active screening for enteric VRE colonization during the study period, VRE screening was carried out on all stools sent for Data analysis Clostridium difficile testing. The standard antibiotic regi- Risk factors for death were analyzed by the Student’s t-test mens for neutropenic fever during the study period or Mann–Whitney U-test for continuous variables and the 2 consisted of cefepime monotherapy (ceftazidime from w test for categorical variables. Kaplan–Meier analysis was February 1996 to January 1998) for leukemics, autologous, used to calculate median survival after VRE BSI. Back- and sibling allogeneic transplants recipients and imipenem wards, stepwise Cox proportional hazards (Pp0.05 for plus vancomycin for unrelated donor allogeneic recipients. entry, PX0.1 for exclusion) were used to determine risk Washington University School of Medicine Human Studies factors for death at discharge on multivariable analysis. Committee approval was obtained for this study. For measures of association, a two-tailed Pp0.05 was Chart review was conducted with a standardized data considered to be significant. collection tool. Patient-related variables collected at the time of the VRE BSI included: age, underlying disease, stage of underlying disease, transplant history, Eastern Results Cooperative Oncology Group (ECOG) score on admission and at time of the VRE BSI, co-morbidities, graft- Epidemiological characteristics of VRE colonization versus-host disease (GVHD), immunosuppressant drugs, and BSI APACHE II score 48 h before and at the time of VRE BSI During the 83-month-study period 334 patients screened and discharge status. All inpatient antibiotics, chemo- positive for enteric VRE colonization. Sixty-eight episodes therapeutic agents and infections were collected if of VRE BSI were observed in 60 patients (for patients present within 42 days before the VRE BSI. Antibiotic with 41 VRE BSI only data from the first VRE BSI are exposures were aggregated by type of coverage (gram described from this point forward). The incidence of VRE positive, gram negative, anaerobic and fungal) as described BSI ranged between 0.6 and 0.9 VRE BSI/1000 patient days previously.17,23 Vancomycin exposure was also reported from 1996 to 1998 (Figure 1). During this period it was separately. hospital policy for all health-care workers to wear gowns and gloves before entering the room of patients colonized with VRE. In 1998 this policy was changed to gloves alone. Study definitions This was followed by a sharp rise in the rate to 2.1 VRE Episodes of VRE BSI were prospectively identified by the BSI/1000 patient-days in 2001. As a result of this increase, Infection Control Department at Barnes-Jewish Hospital. gowns and gloves were reinstituted and the rate regressed A VRE BSI was defined as X2 sets of blood cultures back to 1.3 VRE BSI/1000 patient-days. positive for VRE drawn within 24 h of each other or one set of blood cultures positive and the presence of fever 1 (438.0 C), chills or hypotension when cultures were VRE BSI Rate from 1996 through 2002 drawn. Infections were considered secondary if the same Gown use re-instituted for organism was cultured from another site, other than stool, 2.5 VRE precautions within the previous 48 h. Bloodstream infections were considered polymicrobial if more than one organism grew 2.0 from the same set of blood cultures. VRE BSIs were considered recurrent if VRE was isolated from blood 1.5 Gown use discontinued cultures after treatment with
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