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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 -resistant enterococcal bacteremia following autologous peripheral 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 , and empiric use of of high-dose (HDC) and autologous peri- broad-spectrum . 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- 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), leukemia the first 2 weeks following PBSCT. Transplant-related mor- (n = 14), ovarian (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, 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, 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 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 count organism-associated precautions in addition to the universal (ANC) Ͼ 1 × 109/l) or initiation of parenteral for precautions already described. Hospital personnel and visi- . 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 by means of the Sensititre Underlying diagnoses and time of onset of VRE bacteremia Microbroth Dilution System (Trek Diagnostic Systems, in relation to PBSCT in patients who developed VRE bac- Westlake, OH, USA) and interpreted according to the teremia are outlined in Table 2. Surveillance cultures for guidelines of the National Committee for Clinical and Lab- VRE were instituted in April 1998. A total of 29 patients oratory Standards (NCCLS).8,9 Vancomycin resistance was underwent HDC/PBSCT between April 1998, and August defined as MIC Ͼ16 ␮g/ml. Gentamicin-resistance was 1998. Fifteen of these individuals were found to be defined as MIC Ͼ500 ␮g/ml. During aplasia, all febrile epi- colonized by VRE, and four of these 15 patients went on sodes were treated initially with empiric ceftazidime 1 g to develop VRE bacteremia (patients 7, 8, 9 and 10). i.v. every 8 h with or without vancomycin 1 g i.v. every Patients 1 and 2 developed bacteremia in August 1995 and 12 h. The antibiotic regimen was altered in accordance with May 1996, respectively. Patients 3, 4 and 5 were clustered the susceptibility of any organisms that were identified sub- between April and June 1997. However each patient was sequently. Vancomycin-resistant enterococcus bacteremia admitted to a separate room. Similarly, patients 6–10 were

Bone Marrow Transplantation VRE after autologous stem cell transplant D Kapur et al 149 Table 2 Clinical features and outcome

Diagnosis Days post Empiric antibiotic therapy Treatment Result PBSCT

1 Multiple myeloma 10 Vancomycin, Ceftazidime LD, GEN, C, VRE persistent, died of CHL, SYN enterococcal endocarditis, nearly 2 years post PBSCT 2 Metastatic bladder 12 Vancomycin, Ceftazidime, Tobramycin, LD, BACIT, C VRE persistent, died of other carcinoma Metroindazole causes 3 Recurrent medulloblastoma 4 Vancomycin, Ceftazidime, Tobramycin LD, DOX, RIF, VRE resolved GEN, BACIT 4 Recurrent ovarian CA 6 Vancomycin, Ceftazidime RIF VRE resolved 5 Non-Hodgkin’s lymphoma 7 Vancomycin, Ceftazidime, Tobramycin LD VRE resolved 6 Metastatic breast cancer 5 Vancomycin, Ceftazidime, LD, GEN VRE resolved 7 Metastatic breast cancer 10 Vancomycin, Ceftazidime LD, DOX, CHL, VRE resolved SYN 8 Metastatic breast cancer 6 Vancomycin, Ceftazidime LD, CHL VRE resolved 9 Recurrent Ewing’s sarcoma 5 Vancomycin, Ceftazidime, NIT VRE resolved 10 Non-Hodgkin’s lymphoma 6 Vancomycin, Ceftazidime, CHL VRE persistent, died of other causes

LD = lines discontinued; CHL = chloramphenicol; RIF = rifampin; GEN = gentamicin; VANC = vancomycin; NIT = nitrofurantoin; BACIT = Bacitracin; C = Co-trimoxazole; DOX = doxycycline; SYN = Synercid. clustered between March and May 1997, and were also lated from culture of any of these specimens despite co- each admitted to separate, non-overlapping rooms. existent bacteremia. Vancomycin-resistant enterococcal bacteremia resolved in one patient following removal of Clinical features, treatment and outcome the central venous catheter without the need for antibiotic therapy. Bacteremia resolved completely without adverse Fever was the presenting feature in all 10 patients. Clinical sequelae in seven individuals. Two patients with persistent features and outcomes of VRE bacteremia are outlined in or relapsed VRE bacteremia died of other causes Table 3. The organism was isolated from the blood stream (anthracycline cardiomyopathy and pneu- on more than one occasion (Ͼ1 day) in six individuals. monitis, respectively). One patient, who failed a full course In vitro antibiotic susceptibility test results are outlined in of treatment with quinupristin/dalfopristin, developed Table 4. All strains of VRE were multiply drug resistant. numerous relapses of VRE bacteremia and died of VRE The following antibiotics were utilized in the management endocarditis 605 days following PBSCT. of VRE bacteremia: chloramphenicol 12.5 mg/kg i.v. every 6 h for 1 week in four patients; doxycycline 100 mg orally twice daily for 1 week in two patients; bacitracin 50 000 Discussion units orally four times daily for 2 weeks in two patients; quinupristin/dalfopristin 7.5 mg/kg i.v. every 8 h for 6 Enterococci are facultative anaerobic, gram-positive cocci weeks in two patients; rifampin 300 mg orally or i.v. twice seen microscopically either singly or in pairs and chains. daily for 4 weeks in two patients; co-trimoxazole 5 mg/kg They exist in humans as normal commensals of the gastro- (of trimethoprim) every 6 h for 1 week in two patients; and intestinal and vaginal tracts, and the oral cavity. Normally, nitrofurantoin 100 mg orally every 6 h for 10 days in one E. faecalis and E. faecium constitute 80–90% and 10–15%, patient. Four patients received more than one antimicrobial respectively, of all enterococcal species isolated from cul- agent. The central venous catheter was removed in seven ture.10 However, the incidence of E. faecium, especially of patients but was retained in three other individuals without drug resistant strains, is increased markedly in immuno- complications. The catheter tip was submitted for culture compromised patients such as organ transplant recipients in these seven patients. However, VRE could not be iso- and individuals with acute leukemia and neutropenia.11–14 All 10 individuals reported in the current study developed VRE bacteremia within 2 weeks of autologous PBSCT. Table 3 Clinical features and outcome – summary Ninety percent of isolates were E. faecium. The myelo- ablative regimens utilized in our study were particularly Number of patients with VRE bacteremia 10 Enteroccoccus faecium:E. Faecalis 9:1 toxic to the gut. All 10 patients who developed VRE bacter- Median day after transplant when VRE was isolated 6 (4–12) emia also developed severe stomatitis and diarrhea. It is Median interval from first to last positive blood 5 (1–605) possible that VRE species were translocated from the gut cultures in days into the blood stream after the development of severe Resolution of bacteremia 9 mucositis within the gastro-intestinal tract. Once within the Relapse of bacteremia following resolution 2 Presence of bacteremia at the time of death 3 circulation, VRE organisms may have colonized the Mortality from VRE 1 indwelling catheter of an occasional patient. Enterococci are responsible for at least 12% of all noso- VRE = vancomycin-resistant enterococcus. comial infections and 8% of all nosocomial bacteremias.4

Bone Marrow Transplantation VRE after autologous stem cell transplant D Kapur et al 150 Table 4 In vitro antibiotic suceptibility

Drug MIC (␮g/ml) Patient number

12345678910

Vancomycin Ͼ64(R) Ͼ64(R) 64(R) Ͼ64(R) Ͼ64(R) Ͼ16(R) Ͼ16(R) Ͼ16(R) Ͼ16(R) Ͼ16(R) Ampicillin Ͼ16(R) Ͼ16(R) 32(R) Ͼ16(R) Ͼ16(R) Ͼ8(R) Ͼ8(R) Ͼ8(R) Ͼ8(R) Gentamicin Ͼ500(R) Ͼ500(R) Ͼ500(R) Ͼ500(R) Ͼ500(R) Ͼ500(R) Tobramycin 16(R) Ciprofloxacin Ͼ4(R) Ͼ4(R) Ͼ4(R) Ͼ4(R) Ͼ4(R) Ͼ2(R) Ͼ2(R) Ͼ2(R) Ͼ2(R) Cefazolin Ͼ128(R) Ͼ16(R) Ͼ16(R) Ͼ16(R) Chloramph Ͻ4(S) 8(S) Ͻ4(S) Ͻ4(S) Ͻ4(S) Ͻ4(S) Tetracycline Ͻ0.25(S) Ͻ0.25(S) Nitrofurantoin Ͻ32(S) 64(I) Ͻ32(S) 64(I) Rifampin 1(S) Ͻ0.5(S) Synercid SS Teichoplanin Ͻ0.12(S)

R = resistant; S = susceptible; I = intermediate; Chloramph = chloramphenicol.

The emergence of drug resistant strains has limited treat- bacitracin25 have also been used to treat VRE infection. ment options. Resistance to vancomycin is generally asso- Oral bacitracin was utilized in the treatment of two of our ciated with resistance to aminoglycosides and ampicillin patients with persistent bacteremia as an adjunct to other making these organisms virtually untreatable with com- anti-microbial agents. The rationale was based on previous monly utilized antimicrobial chemotherapy.15,16 At present, reports suggesting reduction or elimination of fecal carriage VRE is a common intestinal colonizer among hospitalized of VRE following the administration of oral bacitracin.25,26 individuals.5 Vancomycin-resistant E. faecium has been iso- Since it is our assumption that the primary source of VRE lated increasingly among patients in intensive care was the gastro-intestinal tract in our patients, oral bacitracin units.11,12 Furthermore, VRE faecium has also been associa- was utilized in an effort to decrease the VRE bacterial load ted with an increased incidence of bacteremia17,18 and mor- in the gut. It must be stated that oral bacitracin, an agent tality.19 Enterococci readily acquire antibiotic resistant that is not absorbed from the gut, was not used to treat the genes and elaborate substances which promote adherence actual VRE bacteremia. Similarly, nitrofurantoin has been to host tissues, induce tissue damage, and produce inflam- utilized previously to treat urinary tract infections due to matory reactions.10 Risk factors predicting the acquisition VRE.27 However, there does not appear to be any basis for of VRE include the presence of a central venous catheter, its use in the treatment of VRE bacteremia. More recently, neutropenia,20 intestinal colonization,5,17 recent or current quinupristin/dalfopristin (Synercid; Rhone-Poulenc-Rorer administration of vancomycin, third generation cephalo- Pharmaceuticals, Collegeville, PA, USA) has been a valu- sporins, , clindamycin or imipenem,5,17,21 able addition to the armamentarium.28 However, there is no severity of underlying disease,5 7 or more days of hospi- definite strategy outlining the optimal type and duration of talization especially in a surgical ICU,21 more than 7 days treatment. Unfortunately, mortality from VRE bacteremia of vancomycin use,21 and transfer between floors.21 Most and infection is still considerable despite appropriate man- of the patients in the current study were neutropenic and agement.19,29 In a recent study, 20 of 56 patients colonized all were severely immuno-compromised. Numerous anti- by VRE developed bacteremia.30 Unlike our patients, the biotics, including vancomycin, had been initiated empiri- majority of these patients had undergone allogeneic trans- cally prior to the isolation VRE bacteremia. Every individ- plantation (n = 43). Seventeen of these 20 patients with ual had already been hospitalized for Ͼ7 days in a bone VRE bacteremia died, 16 as a result of non-relapse mor- marrow transplant unit. Moreover, every individual had an tality. The authors concluded that VRE infection and bac- indwelling central venous catheter and was suffering from teremia was associated with a high mortality rate and may a potentially lethal malignancy. be associated with an increased risk for graft failure. There- The treatment of VRE bacteremia poses a unique set of fore, it is surprising that the mortality from VRE bacteremia challenges. Indwelling central venous catheters should be in our group of patients was only 10% and transplant- removed as soon as possible. Surprisingly, VRE could only related mortality was only 20% in these 10 individuals. be cultured from the catheter tip of one out of seven of our Enterococci are likely spread by hospital personnel.31,32 patients in whom the central line was removed. However, These organisms have been identified on doors, bedrails, clinical signs and symptoms did improve to some extent in linen, electronic thermometers, electrocardiography moni- the majority of these seven patients following the removal tors and sphygmomanometer cuffs.33–35 Various strategies of their central catheters, and bacteremia resolved in one have been employed to reduce nosocomial spread of VRE. patient without the need for anti-microbial therapy. Chlor- These include strict hand washing by hospital employees amphenicol 500–1000 mg i.v. every 6 h has been utilized with antiseptic soaps, restriction of empiric vancomycin with moderate success and without any significant and irre- usage, and performance of weekly stool surveillance culture versible adverse hematologic sequelae.22 Other agents such for VRE among hospitalized patients. All individuals as doxycycline,23 nitrofurantoin,24 co-trimoxazole and oral colonized with VRE should be cared for with strict barrier

Bone Marrow Transplantation VRE after autologous stem cell transplant D Kapur et al 151 precautions, including the use of gloves and gowns.36 13 Chadwick PR, Oppenheim BA, Fox A et al. Epidemiology of Unfortunately, one large study failed to demonstrate an outbreak due to glycopeptide-resistant Enterococcus faec- any reduction in the rate of VRE colonization despite the ium on a leukemia unit. J Hosp Infect 1996; 34: 171–182. institution of these precautions.5 14 Papanicolaou GA, Meyers BR, Meyers J et al. Nosocomial The current study is the first to ascertain the incidence infections with vancomycin-resistant Enterococcus faecium in liver transplant recipients: risk factors for acquisition and mor- and outcome of VRE bacteremia following HDC/PBSCT. tality. Clin Infect Dis 1996; 23: 760–766. Bacteremia resolved without relapse in 70% of patients. 15 Spera RV Jr, Farber BF. Multiply-resistant Enterococcus faec- Numerous antimicrobial agents were utilized singly or in ium. The nosocomial pathogen of the 1990s. JAMA 1992; 268: combination but their role in resolving VRE bacteremia is 2563–2564. unclear. Furthermore, the optimal antimicrobial agent and 16 Montecalvo MA, Horowitz H, Gedris C et al. Outbreak of duration of therapy have not been defined in patients vancomycin-, ampicllin-, and aminoglycoside-resistant undergoing HDC/PBSCT. Surprisingly, three patients Enterococcus faecium bacteremia in an adult unit. cleared their bloodstream of enterococci without removal Antimicrob Agents Chemother 1994; 38: 1363–1367. of their central venous catheter. Most instances of VRE 17 Edmond MB, Ober JF, Weinbaum DL et al. Vancomycin- bacteremia resolved following recovery of the ANC. How- resistant Enterococcus faecium bacteremia: risk factors for ever, because effective antimicrobial agents against VRE infection. Clin Infect Dis 1995; 20: 1126–1133. 18 Patterson JE, Sweeny AH, Simms M et al. An analysis of 110 are lacking, successful preventive strategies need to be serious enteroccoccal infections. 1995; 75: 191–200. developed. For now, we perform weekly stool surveillance 19 Linden PK, Pasculle AW, Manez R et al. Differences in out- cultures for VRE among all hospitalized patients in our comes for patients with bacteremia due to vancomycin-resist- bone marrow transplant unit and apply strict barrier pre- ant Enterococcus faecium or vancomycin-susceptible E. faec- cautions in those individuals in whom stool colonization ium. Clin Infect Dis 1996: 22: 663–670. has been identified. Furthermore, the empiric use of 20 Elishoov H, Or R, Strauss N et al. Nosocomial colonization, parenteral and oral vancomycin has been restricted. septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplantation recipients: a 5 year prospective study. Medicine 1998; 77: 83–101. References 21 Tornieporth NG, Roberts RB, John J et al. Risk factors asso- ciated with vancomycin-resistant Enterococcus faecium infec- 1 Englehard D, Monks MI, Good RAE. Infections in bone mar- tion or colonization in 145 matched case patients and control row transplant recipients. J Pediatr 1986; 108: 335–346. patients. Clin Infect Dis 1996; 23: 767–772. 2 Walter EA, Bowden RA. Infections in the bone marrow trans- 22 Norris AH, Reilly JP, Edelstein PH et al. Chloramphenicol for plant recipient. Infect Dis Clin North Am 1995; 4: 823–847. the treatment of vancomycin-resistant enterococcal infections. 3 Bilgrami S, Feingold JM, Dorsky D et al. Streptococcus virid- Clin Infect Dis 1995; 20: 1137–1144. ans bacteremia following autologous peripheral blood stem 23 Moreno F, Jorgensen JH, Weiner MH. An old antibiotic for cell transplantation. Bone Marrow Transplant 1998; 21: a new multiple-resistant Enterococcus faecium. Diagn 591–595. Microbiol Infect Dis 1994; 20: 41–43. 4 Schaberg DR, Culver DH, Gaynes RP. 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Treatment of vancomycin-resistant Enterococcus fae- chemotherapy with autologous peripheral blood stem cell cium infections. Arch Intern Med 1996; 156: 2579–2584. transplantation for metastatic breast cancer: immunologic 28 Eliopoulos GM, Wennersten CB, Gold HS et al. Characteriz- consequences affecting clinical outcome. Bone Marrow Trans- ation of vancomycin-resistant Enterococcus faecium isolates plant 1999; 24: 837–843. from the United States and their susceptibility in vitro to dal- 8 National Committee for Clinical Laboratory Procedures. fopristin-quinupristin. Antimicrob Agents Chemother 1998; Methods for Dilution Antimicrobial Susceptibility Tests for 42: 1088–1092. that Grow Aerobically, 3d edn. National Committee 29 Centers for Disease Control and Prevention. Nosocomial for Clinical Laboratory Standards: Villanova, PA, 1993. enterococci resistant to vancomycin – United States 1989– 9 National Committee for Clinical Laboratory Procedures. Per- 1993. 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Bone Marrow Transplantation VRE after autologous stem cell transplant D Kapur et al 152 Enterococcus faecalis among patients and staff of an - 35 Boyce JM, Opal SM, Chow JW et al. Outbreak of multidrug- toddler surgical ward. New Engl J Med 1990; 323: 1814–1818. resistant Enterococcus faecium with transferable vanB class 33 Karanfil LV, Murphy M, Josephson A et al. A cluster of van- vancomycin resistance. J Clin Microbiol 1994; 32: 1148– comycin-resistant Enterococcus faecium in an intensive care 1153. unit. Infect Control Hosp Epidemiol 1992; 13: 195–200. 36 Hospital Infection Control Practices Advisory Committee 34 Livornese LL Jr, Dias S, Samel C et al. Hospital-acquired (HICPAC). Recommendations for preventing the spread of infection with vancomycin-resistant Enterococcus faecium vancomycin resistance. Infect Control Hosp Epidemiol 1995; transmitted by electronic thermometers. Ann Intern Med 1992; 16: 105–113. 117: 112–116.

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