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Incidence and Outcome of Vancomycin-Resistant Enterococcal Bacteremia Following Autologous Peripheral Blood Stem Cell Transplantation

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Incidence and Outcome of Vancomycin-Resistant Enterococcal Bacteremia Following Autologous Peripheral Blood Stem Cell Transplantation Bone Marrow Transplantation (2000) 25, 147–152 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt Incidence and outcome of vancomycin-resistant enterococcal bacteremia following autologous peripheral blood stem cell transplantation D Kapur, D Dorsky, JM Feingold, RD Bona, RL Edwards, J Aslanzadeh, PJ Tutschka and S Bilgrami Bone Marrow Transplant Program, University of Connecticut Health Center, Farmington, CT, USA Summary: sive use of central venous catheters, selective gut decon- tamination which is directed towards the prevention of A retrospective evaluation of 321 consecutive recipients gram-negative bacterial infections, and empiric use of of high-dose chemotherapy (HDC) and autologous peri- broad-spectrum antibiotic therapy. Enterococci are pheral blood stem cell transplantation (PBSCT) was important pathogens and have emerged as the second most conducted to ascertain the incidence and outcome of common cause of nosocomial infections in the USA.4–6 The vancomycin-resistant enterococcal (VRE) bacteremia. emergence of strains of enterococci which are resistant to Ten patients developed VRE bacteremia at a median of conventional antibiotic therapy is of particular concern. 6 days following PBSCT. Nine isolates were Entero- Infection with vancomycin-resistant enterococcus (VRE) coccus faecium and one was E. faecalis. The median species in severely immuno-compromised individuals, such duration of bacteremia was 5 days. The central venous as those who have recently undergone HDC followed by catheter was removed in seven individuals. Nine allogeneic or autologous transplantation, has the potential patients were treated with a variety of antimicrobial for significant morbidity and mortality. A substantial period agents including quinupristin-dalfopristin, chloram- of immunologic dysfunction follows HDC/PBSCT7 in phenicol, doxycycline, oral bacitracin, co-trimoxazole, addition to nearly 1 week of profound neutropenia immedi- and nitrofurantoin. Bacteremia resolved without ately following autologous stem cell infusion. The aim of adverse sequelae in seven patients. Two individuals who the current study was to ascertain the incidence and out- died of other causes had persistent or relapsed bactere- come of VRE bacteremia following HDC/PBSCT. mia at the time of death. An additional patient suffered multiple relapses of VRE bacteremia and died as a result of VRE endocarditis 605 days following PBSCT. Patients and methods Mortality as a direct result of VRE bacteremia was 10% in this series. The optimal type and duration of treat- Three hundred and twenty one consecutive patients who ment of VRE bacteremia has not been clearly defined. underwent HDC/PBSCT between March 1993 and August Therefore, we perform weekly stool surveillance cul- 1998 at the University of Connecticut Health Center, Farm- tures for VRE in our hospitalized transplant population ington, CT, USA, were eligible for this retrospective evalu- and apply strict barrier precautions in those individuals ation. Clinical data were obtained from comprehensive in whom stool colonization has been identified. Further- chart reviews (Table 1). more, the empiric use of vancomycin has been Underlying malignancies included carcinoma of the restricted. Bone Marrow Transplantation (2000) 25, 147–152. Table 1 Patient characteristics Keywords: vancomycin-resistant enterococcus; auto- logous stem cell transplant All patients Patients with VRE Number of patients 321 10 Gram-positive bacterial infections are a major cause of sig- Median age in years (range) 44 (1–66) 45 (20–56) nificant morbidity following bone marrow transplantation, Male:Female 94:227 3:7 and high-dose chemotherapy with autologous peripheral Solid tumor:hematologic 185:136 7:3 1–3 malignancy blood stem cell transplantation (HDC/PBSCT). Several BUCAT:other conditioning 198:123 4:6 factors seem to contribute to the increasing incidence of regimens infection by gram-positive organisms including the exten- Median duration of neutropenia in 7 (3–12) 7 (5–9) days (range) Median day of engraftment (range) +9(+7to+13) +9(+8to+11) Correspondence: Dr S Bilgrami, MC-1315, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA VRE = vanomycin-resistant enterococcus; BUCAT = busulfan, carbo- Received 20 May 1999; accepted 5 September 1999 platin, thiotepa. VRE after autologous stem cell transplant D Kapur et al 148 breast (n = 155), non-Hodgkin’s lymphoma and Hodgkin’s was defined as at least one positive blood culture during disease (n = 98) multiple myeloma (n = 24), acute leukemia the first 2 weeks following PBSCT. Transplant-related mor- (n = 14), ovarian cancer (n = 9), and miscellaneous solid tality was defined as death during the first 100 days follow- tumors (n = 21). The HDC regimen consisted of busulfan ing stem cell infusion from causes other than relapse of the 16 mg/kg body weight orally, carboplatin 800–1000 mg/m2 underlying malignancy. i.v., and thiotepa 500–700 mg/m2 i.v. (BUCAT) (n = 198); Any individual undergoing HDC/PBSCT was admitted busulfan 16 mg/kg body weight orally, cyclophosphamide to a hepa-filtered room with an attached bathroom which 90 mg/kg i.v., and etoposide 60 mg/kg i.v. (BUCET) was not shared with other patients. Strict protective iso- (n = 105); and other regimens (n = 18). lation was enforced. Hospital personnel and visitors were A Hickman-type double- or triple-lumen central venous required to wash their hands with a disinfectant soap prior catheter was inserted prior to HDC/PBSCT. Specialists in to entering any room. Additionally, gloves, gown and mask oral diagnosis evaluated all patients, and any corrective had to be worn if the patient’s ANC was Ͻ0.5 × 109/l. dental surgery was performed at least 2 or 3 months prior Patients were allowed to ambulate within the confines of to PBSCT. During the transplant admission, the oral cavity- the bone marrow transplant unit but were instructed to wear care protocol consisted of liquid nystatin 1 × 106 units gloves, gown and mask if their ANC was Ͻ0.5 × 109/l. swish and expectorate twice daily, and half-strength hydro- Each nurse was entrusted with the care of more than one gen peroxide swish and expectorate four times daily. Anti- patient simultaneously. biotic prophylaxis against gram-negative organisms con- In April 1998, rectal swabs or stool cultures were submit- sisted of ciprofloxacin 500 mg orally twice daily from the ted weekly for culture starting on the day of admission. Any beginning of conditioning chemotherapy (day −7 to day individual colonized by VRE was placed under significant −10) until engraftment (absolute neutrophil count organism-associated precautions in addition to the universal (ANC) Ͼ 1 × 109/l) or initiation of parenteral antibiotics for precautions already described. Hospital personnel and visi- fever. Children under 16 years of age received co-trimox- tors were required to wear gloves, gown and shoe-covers, azole (5 mg/kg of trimethoprim) orally twice daily instead as well as a mask if the patient was neutropenic, before of ciprofloxacin. Additionally, 123 patients were given entering the room of a VRE-positive patient. All gloves and ampicillin 250 mg orally four times daily and 77 patients disposable apparel had to be discarded in a receptacle received clarithromycin 250 mg orally twice daily as within the patient’s room, and hands had to be washed with prophylaxis against gram-positive organisms from day +2 antiseptic soap immediately after emerging from the room. until engraftment or initiation of parenteral antibiotics. Thermometers, stethoscopes, sphygmomanometers, i.v. Compliance with prophylactic oral antibiotic therapy was poles and wheel-chairs were dedicated to the rooms of not an issue because all patients remained hospitalized VRE-positive patients. Daily and terminal cleaning of from day −7or−10 until engraftment. Cotrimoxazole rooms followed previously approved hospital guidelines. (800 mg/160 mg) orally twice daily every Monday and Thursday was initiated following engraftment for prophy- 2 laxis against Pneumocystis carinii. Acyclovir 250 mg/m Results i.v. three times daily was utilized prophylactically from the initiation of conditioning chemotherapy until engraftment Incidence and was then continued orally at a dose of 400 mg orally twice daily until day +50 in all individuals who were Ten patients (3.1%) developed VRE bacteremia at a median sero-positive for Herpes simplex. of 6 days following PBSCT. Species of VRE included E. Blood cultures were obtained for any febrile episode faecium (n = 9) and E. faecalis (n = 1). Only three patients (fever Ͼ38°C) and subsequently as indicated clinically. developed VRE bacteremia following engraftment (two Blood was collected in culture bottles (BACTEC NR-660, patients, 1 day following engraftment; one patient, 3 days Becton Dickinson, Towson, MD, USA) and incubated at following engraftment). Five of 123 patients receiving cip- 35°C. Once a positive reading was obtained, an aliquot rofloxacin and ampicillin prophylactically and five of 77 from each positive bottle was gram-stained and inoculated patients receiving ciprofloxacin and clarithromycin on the appropriate agar media. Following overnight growth developed VRE bacteremia. A comparison of clinical the isolates were speciated utilizing the API Identification characteristics seen in the entire group of patients (n = 321) System (BioMerieux, Hazelwood, MO, USA). Suscepti- and those with VRE bacteremia is presented in Table 1. bility testing was performed
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