Prevention, Diagnosis, and Treatment of Invasive Fungal Infections in Patients with Cancer and Neutropenia

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  • 1 Division of Infectious Diseases, Department of Medicine, School of Medicine and Biomedical Sciences, SUNY at Buffalo, Buffalo, New York

Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.

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Correspondence: Brahm H. Segal, MD, Division of Infectious Diseases, Roswell Park Cancer Institute, Buffalo, NY 14263. E-mail: brahm.segal@roswellpark.org
  • 1

    Bow EJ, Loewen R, Cheang MS. Cytotoxic therapy-induced D-xylose malabsorption and invasive infection during remission-induction therapy for acute myeloid leukemia in adults. J Clin Oncol 1997;15:22542261.

    • Search Google Scholar
    • Export Citation
  • 2

    Pfaller MA, Messer SA, Houston A. National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species. Diagn Microbiol Infect Dis 1998;31:289296.

    • Search Google Scholar
    • Export Citation
  • 3

    Pfaller MA, Jones RN, Messer SA. National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis 1998;31:327332.

    • Search Google Scholar
    • Export Citation
  • 4

    Pfaller MA, Jones RN, Messer SA. National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic. Diagn Microbiol Infect Dis 1998;30:121129.

    • Search Google Scholar
    • Export Citation
  • 5

    Edwards JE Jr, Bodey GP, Bowden RA. International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections [see comments]. Clin Infect Dis 1997;25:4359.

    • Search Google Scholar
    • Export Citation
  • 6

    Viscoli C, Girmenia C, Marinus A. Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 1999;28:10711079.

    • Search Google Scholar
    • Export Citation
  • 7

    Anaissie EJ, Kontoyiannis DP, O'Brien S. Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med 1998;129:559566.

    • Search Google Scholar
    • Export Citation
  • 8

    Thaler M, Pastakia B, Shawker TH. Hepatic candidiasis in cancer patients: the evolving picture of the syndrome. Ann Intern Med 1988;108:88100.

    • Search Google Scholar
    • Export Citation
  • 9

    Karthaus M, Huebner G, Elser C. Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation. Ann Hematol 1998;77:41-45.

    • Search Google Scholar
    • Export Citation
  • 10

    Bjerke JW, Meyers JD, Bowden RA. Hepatosplenic candidiasis—a contraindication to marrow transplantation? Blood 1994;84:281114.

  • 11

    Walsh TJ, Whitcomb PO, Revankar SG, Pizzo PA. Successful treatment of hepatosplenic candidiasis through repeated cycles of chemotherapy and neutropenia. Cancer 1995;76:23572362.

    • Search Google Scholar
    • Export Citation
  • 12

    Pappas PG, Rex JH, Sobel JD. Guidelines for treatment of candidiasis. Clin Infect Dis 2004;38:16189 (Epub 2003 Dec 19).

  • 13

    Rex JH, Bennett JE, Sugar AM. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute (see comments). N Engl J Med 1994;331:13251330.

    • Search Google Scholar
    • Export Citation
  • 14

    Rex JH, Pappas PG, Karchmer AW. A randomized and blinded multicenter trial of high-dose fluconazole (F) + placebo (P) vs. F + amphotericin B (A) as treatment of candidemia in non-neutropenic patients. In: Chicago, IL: 41st Annual ICAAC; December 16–19, 2001.

    • Search Google Scholar
    • Export Citation
  • 15

    Rex JH, Pappas PG, Karchmer AW. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis 2003;36:12211228.

    • Search Google Scholar
    • Export Citation
  • 16

    Anaissie EJ, Vartivarian SE, Abi-Said D. Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a matched cohort study. Am J Med 1996;101:170176.

    • Search Google Scholar
    • Export Citation
  • 17

    Anaissie EJ, Darouiche RO, Abi-Said D. Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis 1996;23:964972.

    • Search Google Scholar
    • Export Citation
  • 18

    Mora-Duarte J, Betts R, Rotstein C. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002;347:20202029.

  • 19

    Walsh TJ, Seibel NL, Arndt C. Amphotericin B lipid complex in pediatric patients with invasive fungal infections. Pediatr Infect Dis J 1999;18:702708.

    • Search Google Scholar
    • Export Citation
  • 20

    Walsh TJ, Whitcomb P, Piscitelli S. Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis. Antimicrob Agents Chemother 1997;41:19441948.

    • Search Google Scholar
    • Export Citation
  • 21

    Walsh TJ, Hiemenz JW, Seibel NL. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis 1998;26:13831396.

    • Search Google Scholar
    • Export Citation
  • 22

    Rex JH, Bennett JE, Sugar AM. Intravascular catheter exchange and duration of candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. Clin Infect Dis 1995;21:994996.

    • Search Google Scholar
    • Export Citation
  • 23

    Cole GT, Halawa AA, Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis 1996;22(suppl 2):S73S88.

    • Search Google Scholar
    • Export Citation
  • 24

    Nucci M, Anaissie E. Revisiting the source of candidemia: skin or gut? Clin Infect Dis 2001;33:19591967.

  • 25

    Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence-based review. Clin Infect Dis 2002;34:591599.

    • Search Google Scholar
    • Export Citation
  • 26

    Gerson SL, Talbot GH, Hurwitz S. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med 1984;100:345351.

    • Search Google Scholar
    • Export Citation
  • 27

    Marr KA, Carter RA, Crippa F. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909917.

    • Search Google Scholar
    • Export Citation
  • 28

    Wald A, Leisenring W, van Burik JA, Bowden RA. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation (see comments). J Infect Dis 1997;175:14591466.

    • Search Google Scholar
    • Export Citation
  • 29

    Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001;32:13191324.

    • Search Google Scholar
    • Export Citation
  • 30

    Grow WB, Moreb JS, Roque D. Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplant 2002;29:1519.

    • Search Google Scholar
    • Export Citation
  • 31

    Jantunen E, Ruutu P, Niskanen L. Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. Bone Marrow Transplant 1997;19:801808.

    • Search Google Scholar
    • Export Citation
  • 32

    McWhinney PH, Kibbler CC, Hamon MD. Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years' experience. Clin Infect Dis 1993;17:397404.

    • Search Google Scholar
    • Export Citation
  • 33

    Yuen KY, Woo PC, Ip MS. Stage-specific manifestation of mold infections in bone marrow transplant recipients: risk factors and clinical significance of positive concentrated smears. Clin Infect Dis 1997;25:3742.

    • Search Google Scholar
    • Export Citation
  • 34

    Marr KA, Carter RA, Boeckh M. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 2002;100:43584366.

    • Search Google Scholar
    • Export Citation
  • 35

    Anaissie EJ, Stratton SL, Dignani MC. Pathogenic Aspergillus species recovered from a hospital water system: a 3-year prospective study. Clin Infect Dis 2002;34:780789.

    • Search Google Scholar
    • Export Citation
  • 36

    Yu VL, Muder RR, Poorsattar A. Significance of isolation of Aspergillus from the respiratory tract in diagnosis of invasive pulmonary aspergillosis. Results from a three-year prospective study. Am J Med 1986;81:249254.

    • Search Google Scholar
    • Export Citation
  • 37

    Caillot D, Casasnovas O, Bernard A. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 1997;15:139147.

    • Search Google Scholar
    • Export Citation
  • 38

    Kuhlman JE, Fishman EK, Burch PA. Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest 1987;92:9599.

    • Search Google Scholar
    • Export Citation
  • 39

    Bretagne S, Costa JM, Bart-Delabesse E. Comparison of serum galactomannan antigen detection and competitive polymerase chain reaction for diagnosing invasive aspergillosis. Clin Infect Dis 1998;26:14071412.

    • Search Google Scholar
    • Export Citation
  • 40

    Maertens J, Verhaegen J, Lagrou K. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 2001;97:16041610.

    • Search Google Scholar
    • Export Citation
  • 41

    Maertens J, Van Eldere J, Verhaegen J. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002;186:12971306.

    • Search Google Scholar
    • Export Citation
  • 42

    Herbrecht R, Letscher-Bru V, Oprea C. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol 2002;20:18981906.

    • Search Google Scholar
    • Export Citation
  • 43

    INFO-FDA. FDA clears rapid test for Aspergillus infection. Available at: http://www.fda.gov/bbs/topics/NEWS/2003/NEW00907.html. Accessed July 2004.

    • Search Google Scholar
    • Export Citation
  • 44

    Sulahian A, Touratier S, Ribaud P. False positive test for Aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med 2003;349:23662367.

    • Search Google Scholar
    • Export Citation
  • 45

    Ascioglu S, Rex JH, de Pauw B. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002;34:714.

    • Search Google Scholar
    • Export Citation
  • 46

    Walsh TJ, Finberg RW, Arndt C. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 1999;340:764771

    • Search Google Scholar
    • Export Citation
  • 47

    Bowden R, Chandrasekar P, White MH. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis 2002;35:359366 (Epub 2002 Jul 25).

    • Search Google Scholar
    • Export Citation
  • 48

    Chopra R. AmBisome in the treatment of fungal infections: the UK experience. J Antimicrob Chemother 2002;49(suppl 1):4347.

  • 49

    Mills W, Chopra R, Linch DC, Goldstone AH. Liposomal amphotericin B in the treatment of fungal infections in neutropenic patients: a single-centre experience of 133 episodes in 116 patients. Br J Haematol 1994;86:754760.

    • Search Google Scholar
    • Export Citation
  • 50

    Herbrecht R, Denning DW, Patterson TF. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408415.

    • Search Google Scholar
    • Export Citation
  • 51

    Denning DW, Ribaud P, Milpied N. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002;34:563571.

    • Search Google Scholar
    • Export Citation
  • 52

    Troke PF, Schwartz S, Ruhnke M. Voriconazole (VCR) therapy (Rx) in 86 patients (pts) with CNS aspergillosis (CNSA): a retrospective analysis. In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 2003.

    • Search Google Scholar
    • Export Citation
  • 53

    Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 1996;23:608615.

  • 54

    Walsh TJ, Lutsar I, Driscoll T. Voriconazole in the treatment of aspergillosis, scedosporiosis, and other invasive fungal infections in children. Pediatr Infect Dis J 2002;21:240248.

    • Search Google Scholar
    • Export Citation
  • 55

    Steinbach WJ, Benjamin DK Jr, Kontoyiannis DP. Invasive aspergillosis (IA) caused by Aspergillus terreus: multicenter retrospective analysis of 87 cases. In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 2003.

    • Search Google Scholar
    • Export Citation
  • 56

    Kartsonis N, Saah A, Lipka J. Salvage therapy (Rx) with Caspofungin (CAS) for invasive aspergillosis (IA): results from the CAS compassionate use (CU) study. In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 2003.

    • Search Google Scholar
    • Export Citation
  • 57

    Caspofungin (Cancidas) for aspergillosis. Med Lett Drugs Ther 2001;43:5859.

  • 58

    Gea-Banacloche JC, Peter J, Bishop M. Successful treatment of invasive aspergillosis with the combination of voriconazole and caspofungin: correlation with in vitro interactions. In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 2003.

    • Search Google Scholar
    • Export Citation
  • 59

    Kontoyiannis DP, Hachem R, Lewis RE. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer 2003;98:292299.

    • Search Google Scholar
    • Export Citation
  • 60

    Aliff TB, Maslak PG, Jurcic JG. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer 2003;97:10251032.

    • Search Google Scholar
    • Export Citation
  • 61

    Offner F, Cordonnier C, Ljungman P. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis 1998;26:10981103.

    • Search Google Scholar
    • Export Citation
  • 62

    Goodman JL, Winston DJ, Greenfield RA. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation (see comments). N Engl J Med 1992;326:845851.

    • Search Google Scholar
    • Export Citation
  • 63

    Slavin MA, Osborne B, Adams R. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis 1995;171:15451552.

    • Search Google Scholar
    • Export Citation
  • 64

    Marr KA, Seidel K, Slavin MA. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood 2000;96:20552061.

    • Search Google Scholar
    • Export Citation
  • 65

    Bow EJ, Laverdiere M, Lussier N. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer 2002;94:32303246.

    • Search Google Scholar
    • Export Citation
  • 66

    Viscoli C, Paesmans M, Sanz M. Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients. Clin Infect Dis 2001;32:15321537.

    • Search Google Scholar
    • Export Citation
  • 67

    Rotstein C, Bow EJ, Laverdiere M. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis 1999;28:331340.

    • Search Google Scholar
    • Export Citation
  • 68

    Winston DJ, Chandrasekar PH, Lazarus HM. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial (see comments). Ann Intern Med 1993;118:495503.

    • Search Google Scholar
    • Export Citation
  • 69

    Kern W, Behre G, Rudolf T. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia: results of a prospective randomized phase III study. German AML Cooperative Group. Cancer 1998;83:291301.

    • Search Google Scholar
    • Export Citation
  • 70

    Marr KA, Seidel K, White TC, Bowden RA. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 2000;181:309316.

    • Search Google Scholar
    • Export Citation
  • 71

    Zhou H, Goldman M, Wu J. A pharmacokinetic study of intravenous itraconazole followed by oral administration of itraconazole capsules in patients with advanced human immunodeficiency virus infection. J Clin Pharmacol 1998;38:593602.

    • Search Google Scholar
    • Export Citation
  • 72

    Menichetti F, Del Favero A, Martino P. Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto. Clin Infect Dis 1999;28:250255.

    • Search Google Scholar
    • Export Citation
  • 73

    Morgenstern GR, Prentice AG, Prentice HG. A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haematol 1999;105:901911.

    • Search Google Scholar
    • Export Citation
  • 74

    Foot AB, Veys PA, Gibson BE. Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders. Bone Marrow Transplant 1999;24:10891093.

    • Search Google Scholar
    • Export Citation
  • 75

    Harousseau JL, Dekker AW, Stamatoullas-Bastard A. Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B. Antimicrob Agents Chemother 2000;44:18871893.

    • Search Google Scholar
    • Export Citation
  • 76

    Crippa F, Corey L, Leisenring W. Administration of Itraconazole for antifungal prophylaxis in stem cell transplant recipients: levels and drug interactions. In: Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada; 2000.

    • Search Google Scholar
    • Export Citation
  • 77

    Glasmacher A, Molitor E, Hahn C. Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia. Leukemia 1998;12:13381343.

    • Search Google Scholar
    • Export Citation
  • 78

    Winston DJ, Maziarz RT, Chandrasekar PH. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med 2003;138: 705713.

    • Search Google Scholar
    • Export Citation
  • 79

    Marr KA, Crippa F, Leisenring W. Itraconazole versus fuconazole for prevention of fungal infections in allogeneic stem cell transplant patients. Blood 2003;2:2.

    • Search Google Scholar
    • Export Citation
  • 80

    Marr KA, Leisenring W, Crippa F. Cyclophosphamide metabolism is impacted by azole antifungals. Blood 2003;22:22.

  • 81

    Bodey GP, Anaissie EJ, Elting LS. Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Cancer 1994;73:20992106.

    • Search Google Scholar
    • Export Citation
  • 82

    Mattiuzzi GN, Kantarjian H, Faderl S. Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy. Cancer 2004;100:581589.

    • Search Google Scholar
    • Export Citation
  • 83

    van Burik J, Ratanatharathorn V, Lipton J. Randomized, double-blind trial of Micafungin (MI) versus fluconazole (FL for prophylaxis of invasive fungal infections in patients (pts) undergoing hematopoietic stem cell transplant (HSCT), NIAID/BAMSG protocol 46. In: Annual ICAAC. Chicago, IL; 2002.

    • Search Google Scholar
    • Export Citation
  • 84

    Sullivan KM, Dykewicz CA, Longworth DL. Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond. Hematology (Am Soc Hematol Educ Program) 2001:392421.

    • Search Google Scholar
    • Export Citation
  • 85

    Hahn T, Cummings KM, Michalek AM. Efficacy of high-efficiency particulate air filtration in preventing aspergillosis in immunocompromised patients with hematologic malignancies. Infect Control Hosp Epidemiol 2002;23:525531.

    • Search Google Scholar
    • Export Citation
  • 86

    Carter CD, Barr BA. Infection control issues in construction and renovation. Infect Control Hosp Epidemiol 1997;18:587596.

  • 87

    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 1982;72:101111.

    • Search Google Scholar
    • Export Citation
  • 88

    Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group. Am J Med 1989;86:668672.

    • Search Google Scholar
    • Export Citation
  • 89

    Cagnoni PJ, Walsh TJ, Prendergast MM. Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J Clin Oncol 2000;18:24762483.

    • Search Google Scholar
    • Export Citation
  • 90

    Wingard JR, White MH, Anaissie E. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 2000;31:11551163.

    • Search Google Scholar
    • Export Citation
  • 91

    Boogaerts M, Winston DJ, Bow EJ. Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med 2001;135:412422.

    • Search Google Scholar
    • Export Citation
  • 92

    Winston DJ, Hathorn JW, Schuster MG. A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med 2000;108:282289.

    • Search Google Scholar
    • Export Citation
  • 93

    Viscoli C, Castagnola E, Van Lint MT. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer 1996;32A:814820.

    • Search Google Scholar
    • Export Citation
  • 94

    Walsh TJ, Pappas P, Winston DJ. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002;346:225234.

    • Search Google Scholar
    • Export Citation
  • 95

    Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 2004;350:950952.

    • Search Google Scholar
    • Export Citation
  • 96

    Walsh T, Sable C, DePauw B. A randomized, double-blind, multicenter trial of caspofungin (CS) v liposomal amphotericin B (LAMB) for empirical antifungal therapy (EAFrx) of persistently febrile neutropenic (PFN) patients (Pt). In: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 2003.

    • Search Google Scholar
    • Export Citation
  • 97

    Godwin JE, Kopecky KJ, Head DR. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 1998;91:36073615.

    • Search Google Scholar
    • Export Citation
  • 98

    Heil G, Hoelzer D, Sanz MA. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood 1997;90:47104718.

    • Search Google Scholar
    • Export Citation
  • 99

    Rowe JM, Andersen JW, Mazza JJ. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood 1995;86:457462.

    • Search Google Scholar
    • Export Citation
  • 100

    Ozer H, Armitage JO, Bennett CL. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol 2000;18:35583585.

    • Search Google Scholar
    • Export Citation
  • 101

    Price TH, Bowden RA, Boeckh M. Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoeitic stem cell transplantation. Blood 2000;95:33023309.

    • Search Google Scholar
    • Export Citation
  • 102

    Nichols WG, Price T, Boeckh M. Cytomegalovirus infections in cancer patients receiving granulocyte transfusions. Blood 2002;99:34833484.

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