Advertisement

Neutrophils (granulocytes) are vital components of the effector mechanisms of the host defense. They represent part of the first-line defense against invading microbes (particularly bacteria and fungi), and are essential as part of the innate immune response. Neutrophils circulate as quiescent cells, and their main functions as phagocytic and bactericidal defenders are performed in tissues where microbial invasion occurs. The neutrophil microbicidal defense mechanisms for microbial killing can be either oxidative or non-oxidative. The principal oxidative killing of microbes is via the myeloperoxidase (MPO)–hydrogen peroxide (H2O2) pathway. The microbicidal products generated by the MPO–H2O2 pathway include hypo-chlorous acid, chlorination products, tyrosine radicals, and nitrogen intermediates.1 The neutrophils also produce a host of antimicrobial substances used to fight invading pathogens. These include (1) bacterial permeability-increasing (BPI) protein, which binds to lipopolysaccharide (LPS), with antimicrobial activity against gram-negative bacteria; (2) defensins, small amphipathic pore-forming antibacterial cationic peptides with broad antibacterial spectrum; (3) serine proteases (elastase, cathepsin G) with direct antibacterial activity, besides enzymatic function; (4) lysozyme which cleave peptoglycan-polymers of bacterial cell wall (i.e. gram-positive bacteria); (5) lactoferrin, iron chelator to sequester iron (essential for bacterial growth), but also the proteolytic fragments have direct bactericidal activity; (6) B2 integrins to mediate cellular adhesions and regulate phagocytosis; (7) cathelicidin protein (hcap-18), binds endotoxin, and has antibacterial activity against gram-positive bacteria as well.

The neutrophils also produce a host of antimicrobial substances used to fight invading pathogens. These include (1) bacterial permeability-increasing (BPI) protein, which binds to lipopolysaccharide (LPS), with antimicrobial activity against gram-negative bacteria; (2) defensins, small amphipathic pore-forming antibacterial cationic peptides with broad antibacterial spectrum; (3) serine proteases (elastase, cathepsin G) with direct antibacterial activity, besides enzymatic function; (4) lysozyme which cleave peptoglycan-polymers of bacterial cell wall (i.e. gram-positive bacteria); (5) lactoferrin, iron chelator to sequester iron (essential for bacterial growth), but also the proteolytic fragments have direct bactericidal activity; (6) B2 integrins to mediate cellular adhesions and regulate phagocytosis; (7) cathelicidin protein (hcap-18), binds endotoxin, and has antibacterial activityagainst gram-positive bacteria as well.

Keywords

Febrile Neutropenia Antifungal Therapy Invasive Aspergillosis Invasive Fungal Infection Neutropenic Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Borregaard, N., Boxer, L.A., (2006), Disorders of neutrophil function, in: Williams Hematology, 7th Edition; Lichtman, M.A., Beutler, E., Kipps, T.J., Seligsohn, U., Kaush-ansky, K., Prchal, J.T., (eds); McGraw-Hill Medical, New York, pp. 921–957.Google Scholar
  2. 2.
    Dale, D.C., (2006), Neutropenia and neutrophilia, in: Williams Hematology, 7th Edition; Licktman, M.A., Beutler, E., Kipps, T.J., Seligsohn, U., Kaushansky, K., Prchal, J.T. (eds); McGraw-Hill Medical, New York, pp. 907–919.Google Scholar
  3. 3.
    Marty, F.M., Lee, S.J., Fahey, M.M., Alyea, E.P., Soiffer, R.J., Antin, J.H., Baden, L.R., (2003), Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood 102: 2768–2776.CrossRefPubMedGoogle Scholar
  4. 4.
    Neth, O., Hann, I., Turner, M.W., Klein, N.J., (2001), Deficiency of mannose-binding lectin and burden of infection in children with malignancy: a prospective study. Lancet 358: 614–618.CrossRefPubMedGoogle Scholar
  5. 5.
    Hughes, W.T., Armstrong, D., Bodey, G.P., Bow, E.J., Brown, A.E., Calondra, T., Feld, R., Pizzo, P.A., Rolston, K.V.I., Shenep, J.L., Young, L.S., (2002) 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin. Infect. Dis. 34: 730–751.CrossRefPubMedGoogle Scholar
  6. 6.
    Van der Anwera, P., Gerain, J., (1993), Use of quinolones in the prophylaxis and treatment of granulocytopenic immunocompromised cancer patients. Drugs 45(Suppl 3): 81–90.Google Scholar
  7. 7.
    Viscoli, C., EORTC International Antimicrobial Therapy Group, (2002), Management of infection in cancer patients: studies of the EORTC (International Antimicrobial Therapy Group (IATG). Eur. J. Cancer 38(Suppl 4): S82–S87.CrossRefPubMedGoogle Scholar
  8. 8.
    Viscoli, C., Castagnola, E., (1998), Planned progressive antimicrobial therapy in neutropenic patients. Br. J. Hematol. 102: 879–888.CrossRefGoogle Scholar
  9. 9.
    Wisplinghoff, H., Seifert, H., Werzel, R.P., Edmond, M.P., (2003), Current trends in the epidemiology of noscomial blood stream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin. Infect. Dis. 36: 1103–1110.CrossRefPubMedGoogle Scholar
  10. 10.
    Yadegarynia, D., Turrand, J., Raad, I., Rolston, K., (2003), Current spectrum of bacterial infections in patients with cancer. Clin. Infect. Dis. 7(Suppl): S1144–S1145.CrossRefGoogle Scholar
  11. 11.
    The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer (1993), Efficacy and toxicity of single doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann. Intern. Med. 119: 584–593.Google Scholar
  12. 12.
    Zinner, S.H., (1999), Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria. Clin. Infect. Dis. 29: 490–494.CrossRefPubMedGoogle Scholar
  13. 13.
    Ramphal, R., (2004), Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens. Clin. Infect. Dis. 39(Suppl I): S25–S31.CrossRefPubMedGoogle Scholar
  14. 14.
    Catorratala, J., Fernandez Sevilla, A., Tubau, F., Callis, M., Gudiol, F., (1995), Emergence of quinolone-resistant Escherichia coli bacteremia in neutropenic patients with cancer who have received prophylactic norflxacin. Clin. Infect. Dis. 20: 557–560.Google Scholar
  15. 15.
    Haupt, R., Rumanengo, M., Fears, T., Viscoli C., Castagnola, E., (2001), Incidence of septicemias and invasive mycoses in children undergoing treatment for solid tumors: a 12 year experience at a single Italian institution. Eur. J. Cancer, 37: 2413–2419.CrossRefPubMedGoogle Scholar
  16. 16.
    Gaytan-Martinez, J., Mateos-Garcia, E., Sanchez-Cortes, Gonzalez-Llaven, J., Casanova-Cardiel, L.J., Fuentes-Allen, J.L., (2002), Microbiological findings in febrile neutropenia. Arch. Med. Res. 31: 388–392.CrossRefGoogle Scholar
  17. 17.
    Raje, N.S., Rao, S.R., Iyer, R.S., Kelkar, R.S., Pai, S.K., Nair, C.N., Kurkure, R.A., Magrath, I. T., Advani, S.H., (1994), Infection analysis in acute lymphoblastic leukemia: a report of 499 consecutive episodes in India. Pediatr. Hematol. Oncol. 3: 271–280.Google Scholar
  18. 18.
    Kanamaru, A., Tatsumi, Y., (2004), Microbiological data for patients with febrile neutropenia. Clin. Infect. Dis. 39(Suppl. I) S7–S10.CrossRefPubMedGoogle Scholar
  19. 19.
    Rolston, VI, Bodey, GP, Safdar, A, (2007), Polymicrobial infection in patients with cancer: an under appreciated and underreported entity. Clin. Infect. Dis. 45: 225–233.CrossRefGoogle Scholar
  20. 20.
    Malik, A., Abbas, Z., Karim, M., (1992), Randomized comparison of oral ofloxacin alone with combination of parenteral antibiotics in neutropenic febrile patients. Lancet 339: 1092–1096.CrossRefPubMedGoogle Scholar
  21. 21.
    Malik, I.A., Khan, W.A., Karim, M., Aziz, Z., Khan, M.A. (1995), Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial. Am. J. Med. 98: 224–231.CrossRefPubMedGoogle Scholar
  22. 22.
    Kern, W.V., (2006), Risk assessment and treatment of low-risk patients with febrile neutro-penia. Clin. Infect. Dis. 42: 533–540.CrossRefPubMedGoogle Scholar
  23. 23.
    Klastersky, J., (2004), Management of fever in neutropenic patients with different risks of complications. Clin. Infect. Dis. 39(Suppl 1): S32–S37.CrossRefPubMedGoogle Scholar
  24. 24.
    Vidal, L., Paul, M., Ben-Dor, I., Soares-Weiser, K., Leibovici, L., (2004), Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systemic review and meta-analysis of randomized trials. J. Antimicrob. Chemother: 54: 29–37.CrossRefPubMedGoogle Scholar
  25. 25.
    Sipsas, N.V., Bodey, G.P., Kontoyiannis, D. P., (2005), Perspectives for the management of febrile neutropenic patients with cancer in the 21st century. Cancer 103: 1103–1113.CrossRefPubMedGoogle Scholar
  26. 26.
    Klatersky. J., Paesmans, M., Rubenstein, E.B., Boyer, M., Elting, L., Feld, R., Gallagher, J., Herrstedt, J., Rapoport, B., Rolston, K., Talcott, J; for the Study Section of Multionational Association for Supportive Care in Cancer, (2000), The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J. Clin. Oncol. 18: 3038–3051.Google Scholar
  27. 27.
    Klassen, R.J., Goodman, R., Pham, B.A., Doyle, J.J., (2000), “Low-risk” prediction rule for pediatric oncology patients presenting with fever and neutropenia. J. Clin. Oncol. 18: 1012– 1019.Google Scholar
  28. 28.
    Vidal, L., Paul, M., Ben- Dor, I., Pokroy, E., Soares-Weiser, K., Leibovic L., (2006), Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst. Rev. 3: Access no.00075320–100000000–03018.Google Scholar
  29. 29.
    Paul, M., Soares-Weiser, K., Leibovici., L., (2003), Beta-lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for fever with neutropenia: a systematic review and meta-analysis. B.M.J 326: 1111.CrossRefGoogle Scholar
  30. 30.
    Furno, P., Bucaneve, G., Del Favero, A., (2002), Monotherapy or aminoglycoside- containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analy-sis. Lancet Infect. Dis. 2: 231–242.CrossRefPubMedGoogle Scholar
  31. 31.
    Peacock, J.E., Herrington, D.A., Wade, J.C., Lazarus, H.M., Reed, M.D., Sinclair, J.W., Havestock, D.C., Kowalsky, S.F., Hurd, D.D., Cushing, D.A., Harman, C.P., Donowitz, G. R., (2002), Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial. Ann. Intern. Med. 137: 77–87.PubMedGoogle Scholar
  32. 32.
    Bliziotis, I.A., Michalopoulos, A., Kasiakou, S.K., Samonis, G., Christodoulou, C., Chry-santhopoulou, S., Falagas, M.E., (2005) Ciprofloxacin vs an aminoglycoside in combination with a beta-lactam for the treatment of febrile neutropenia: a meta-analysis of randomized controlled trials. Mayo Clin, Proc. 80: 1146–1156.CrossRefGoogle Scholar
  33. 33.
    Paul, M., Borok, S., Fraser, A., Vidal, L., Cohen, M., Leibovici, L., (2005), Additional anti-Gram-positive antibiotic treatment for febrile neutropenic cancer patients. Cochrane Database Syst. Rev. (3): CD 003914.Google Scholar
  34. 34.
    Hilf, M., Yu, K.L., Sharp, J., Zuravleff, J.J., Korvick, J.A., Muder, R.R., (1989), Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am. J. Med. 83: 119–123.Google Scholar
  35. 35.
    Leibovici, L., Paul, M., Poznanski, O., Drucker, M., Samra, S., Konigsberger, H., Pitlik, S.D., (1997), Monotherapy versus ß-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective observational study. Antimicrob. Agents Chemother. 41: 1127– 1133.PubMedGoogle Scholar
  36. 36.
    Safdar, N., Handelsman, J. Maki, D.G., (2004), Does combination antimicrobial therapy reduce mortality in Gram-negative bacteremia? A meta-analysis. Lancet Infect. Dis. 4: 519–527.CrossRefPubMedGoogle Scholar
  37. 37.
    Chow, J.W., Yu, V.L., (1999), Combination antibiotic therapy versus monotherapy for gram-negative bacteremia: a commentary. Int. J. Antimicrob. Agents 11: 7–12.CrossRefPubMedGoogle Scholar
  38. 38.
    Feld, R., DePauw, B., Berman, S., Keating, A., Ho, W., (2000), Meropenem versus ceftazi-dime in the treatment of cancer patients with febrile neutropenia: a randomized, double blind trial. J. Clin. Oncol 18: 3690–3698.PubMedGoogle Scholar
  39. 39.
    Glasmacher, A., von Lilienfeld., Toal, M., Schulte, S., Hahn, C., Schmidt-Wolf, Prentice, A., (2005), An evidence-based evaluation of important aspects of empirical antibiotic therapy in febrile neutropenic patients. Clin. Microbiol. Infect. 11(Suppl 5): 17–23.CrossRefPubMedGoogle Scholar
  40. 40.
    Cherif, H., Bjorkholm M., Engervall, P., Johansson, P., Ljungmar, P., Hast, R., Kalin, M., (2004), A prospective, randomized study comparing cefepime and imipenem-cilastatin in the empirical treatment of febrile neutropenia in patients treated for haematological malignancies. Scand. J. Infect. Dis. 36: 593–600.CrossRefPubMedGoogle Scholar
  41. 41.
    Tamura, K., Imajo, K., Akiyama, N., Susuki, K., Urabe, A., Ohyashiki, K., Tanimoto, M., Masaoka, T., Japan Febrile Neutropenic Study Group, (2004), Randomized trial of cefepime monotherapy or cefepime in combination with amikacin as empirical therapy for febrile neutropenia Clin. Infect. Dis. 39(Suppl 1): S15–S24.CrossRefPubMedGoogle Scholar
  42. 42.
    Bow, E.J., Rotstein, C., Noskin, G.A., Laverdiere, M., Schwarer, A.P., Segal, B.H., Seymour, J.F. Szer, J., (2006), A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies. Clin. Infect. Dis. 43: 447–459.CrossRefPubMedGoogle Scholar
  43. 43.
    Paul, M., Yahav, D., Fraser, A., Leibovici, I., (2006), Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J. Antimicrob. Chemother. 57: 176–189.CrossRefPubMedGoogle Scholar
  44. 44.
    Harter, C., Schulze, B., Goldschmidt, H., Benner, A., Geiss, H.K., Hoppe-Tichy, T., Ho, A.D., Egerer, G., (2006), Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial. Bone Marrow Transpl. 37: 373–379.CrossRefGoogle Scholar
  45. 45.
    Gorschluter, M., Hahn, C., Fixson, A., Mey, U., Ziske, C., Molitor, E., Horre, R., Sauerbruch, T., Marklein, G., Schmidt-Wolf, I.G., Glasmacher, A., (2003), Piperacillin/tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hemato-logical malignancies: a randomized comparison. Support Care Cancer: 11: 362–370.PubMedGoogle Scholar
  46. 46.
    Del Favero, A., Menichetti, F., Martino, P., Bucaneve, G., Micozzi, A., Gentile, G., Furno, P., Russo, D., (2001), A multicenter, double-blind, placebo-controlled trial comparing piperacil-lin/tazobactam with and without amikacin as empiric therapy for febrile neutropenia. Clin. Infect. Dis. 33: 1295–1301.CrossRefPubMedGoogle Scholar
  47. 47.
    Viscoli, C., Cometta, A., Kern, W.V., Bock, R., Paesmans, M., Crokaert. F., Glauser, M.P., Calandra, T., (2006), Piperacillin/tazobactam monotherapy in high-risk febrile and neutrope-nic cancer patients. Clin. Microbiol. Infect. 12: 212–216.CrossRefPubMedGoogle Scholar
  48. 48.
    Glasmacher, A., von Lilienfeld-Toal, M., Schulte, S., Hahn, C., Schmidt-Wolf, I.G.H., Prentice, C., (2005), An evidence based evaluation of important aspects of empirical antibiotic therapy in febrile neutropenic patients. Clin, Microbiol. Infect. 11(Suppl 5): 17–23.CrossRefGoogle Scholar
  49. 49.
    Elting, L.S., Rubenstein, E.B., Rolston, K., Cantor, S., Martin, G.G., Kurtin, D., Rodriguez, S., Lam, T., Kanesan, K., Bodey, G., (2000), Time to clinical response and outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care. J. Clin. Oncol. 18: 3699–3706.PubMedGoogle Scholar
  50. 50.
    Freifeld, A., Marchigiani, D., Walsh, T., Chanock, S., Lewis, L., Hiemenz, J., Hiemenz S., Hicks, J.E., Gill, V., Steinberg, S.M., Pizzo, P.A., (1999), A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N. Engl. J. Med. 341: 305–311.CrossRefPubMedGoogle Scholar
  51. 51.
    Rolston, K.V.I., (2004), The Infectious Diseases Society of America 2002 Guidelines for the use of antimicrobial agents in patients with cancer and neutropenia: salient features and comments. Clin. Infect. Dis. 39(Suppl 1): S46–S48.Google Scholar
  52. 52.
    Akova, M., Paesmans, M., Calandra, T., Viscoli, C., for the International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer (2005), A European Organization for Research and Treatment of Cancer-International Antimicrobial Therapy Group study of secondary infections in febrile, neutropenic patients with cancer. Clin. Infect. Dis. 40: 239–245.CrossRefPubMedGoogle Scholar
  53. 53.
    Pizzo, P.A., Robichaud, K.J., Gill, F.A., Witebsky, F.G., (1982), Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am. J. Med. 72: 101–111.CrossRefPubMedGoogle Scholar
  54. 54.
    EORTC International Antimicrobial Therapy Cooperative Project Group, (1989), Empiric antifungal therapy in febrile granulocytopenic patients. Am. J. Med. 86: 668–672.CrossRefGoogle Scholar
  55. 55.
    Walsh, J.T., Finberg, R.W., Arndt, C., Hiemenz, J., Schwartz C., Bodensteiner, D., Pappas, P., Seibel, N., Greenberg, R.N., Dummer, S., Schuster, M., Holcenberg, J.S. for the National Institute of Allergy and Infectious Diseases Mycoses Study Group (1999) Liposomal ampho-tericin B empirical therapy in patients with persistent fever and neutropenia, National Institute of Allergy and Infectious Diseases Mycoses Study Group. N. Engl. Med. 340: 764–771.CrossRefGoogle Scholar
  56. 56.
    Wingard, J.R., White, M.H., Anaissie, E., Raffalli, J., Goodman, J. Arrieta, A., and the L-Amph./ABLC Collaborative Study Group, (2000), A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin lipid complex in the empirical treatment of febrile neutropenia. Clin. Infect. Dis. 31: 1155–1163.CrossRefPubMedGoogle Scholar
  57. 57.
    Saral, R., (1991), Candida and aspergillus infections in immunocompromized patients: An overview. Rev. Infect. Dis. 13: 487–492.PubMedGoogle Scholar
  58. 58.
    Horn, R., Wong, B., Kiehn, T.E., Armstrong, D., (1985), Fungemia in a cancer hospital: changing frequency, earlier onset and results of therapy. Rev. Infect. Dis. 7: 646–655.PubMedGoogle Scholar
  59. 59.
    Viscoli, C., Castagnola C., VanLint, M.T., Moroni, C., Gararenta, A., Rossi, M.R., Fanci, R., Menichetti, F., Casselli, D., Giacchino, M., Congiu, M., (1996), Fluconazole versus Ampho-tericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients. Eur. J. Cancer 32A: 814–820.CrossRefPubMedGoogle Scholar
  60. 60.
    Winston, D. J., Hathorn, J. W., Schuster, M.G., Schiller, G. J., Territo, M.C., (2002), A multicenter randomized trial of fluconozole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am. J. Med. 108: 282–289.CrossRefGoogle Scholar
  61. 61.
    Tortorano, A.M., Peman, J., Bernhardt, H., Klingspor, L., Kibbler, C.C., Faure, O., Biraghi, E., Canton, E., Zimmermann, K., Seaton,S., Grillot, R., the ECMM Working Group on Candidaemia, (2004), Epidemiology of candidaemia in Europe: Results of 28 – month European Confederation of Medical Mycology (ECMM) hospital- based surveillance study. Eur. J. Clin. Micriobial Infect. Dis. 23: 317–322.CrossRefGoogle Scholar
  62. 62.
    Pappas, P. G., Rex, J.H., Sobel, J., Filler, S.G., Dismukes, W.E., Walsh, T.J., Edwards, J.E., (2004), Guidelines for treatment of candidiasis. Clin. Infect. Dis. 38: 161–189.CrossRefPubMedGoogle Scholar
  63. 63.
    Boogaerts, M., Winston, D.J., Bow, E.J., Garber, G., Reboli, A.C., Schwarer, A.P., Novitzky, N., Boehome, A., Chwetzoff, E., De Beule, K., and the Intraconazole Neutropenic Study Group, (2001), Intravenous and oral itraconazole versus intravenous amphotericin B deox-ycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. Ann. Intern. Med. 135: 412– 422.PubMedGoogle Scholar
  64. 64.
    Walsh, T.J., Pappas, P., Winston, D.J., Lazarus, H.M., Petersen, F., Raffalli, J., Yanovich, S., Stiff, P., Greenberg, R., Danowitz, G., Schuster, M., Reboli, A., Wingard, J. Arndt, C., Reinhardt, J. Hadley, S., Finberg, R., Laverdierre, M., Perfect, J., Garber, G., Fioritoni, G., Anaissie, E., Lee, J. National Institute of Allergy and Infectious Diseases Mycoses Study Group, (2002), Vorionazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N. Engl. J. Med. 346: 225–234.CrossRefPubMedGoogle Scholar
  65. 65.
    Walsh, T.J., Teppler, H., Donowitz, G.R., Maertens, J.A., Baden, L.R., Dmoszynska, A., Cornely, O.A., Bourque, M.R., Lupinacci, R.J., Sable, C.A., dePauw, B.E., (2004), Caspo-fungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N. Engl. J. Med. 351: 1391–1402.CrossRefPubMedGoogle Scholar
  66. 66.
    Winegard, J.R., (2004), Empirical antifungal therapy in treating febrile neutropenic patients. Clin. Infect. Dis. 39(Suppl): S38–S43.CrossRefGoogle Scholar
  67. 67.
    Martino R., Viscoli, C., (2005), Empirical antifungal therapy in patients with neutropenia and persistent or recurrent fever of unknown origin. Brit. J. Haematol. 132: 138–154.CrossRefGoogle Scholar
  68. 68.
    Sobel, J.D., (2006), Design of Clinical trials of empiric antifungal therapy in patients with persistent febrile neutropenia: considerations and critiques. Pharmacotherapy: 26 (Suppl): 47S–54S.CrossRefPubMedGoogle Scholar
  69. 69.
    Gurwith, M.J., Brunton, J.L., Lank, B.A., Harding, G.K.M., Ronald, A.R., (1979), A prospective contrled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients. Am. J. Med. 66: 248–256.CrossRefPubMedGoogle Scholar
  70. 70.
    Wade, J.C., Schimpff, S.C., Hargadon, M.T., Fortner, C.L., Young, V.M., Wiernik, P.H., (1981), A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N. Engl. J. Med. 304: 1057–1062.PubMedCrossRefGoogle Scholar
  71. 71.
    Dekker, A.W., Rozenberg-Arska, M., Sixma, J.J. Verhoef, J., (1981), Prevention of infection by trimethoprim-sulfamethoxazole plus amphotericin B in patients with acute nonlymphocytic leukemia. Ann. Intern. Med. 95: 555-5591.PubMedGoogle Scholar
  72. 72.
    Wilson, J.M., Guiney, D.G., (1982), Failure of oral trimethoprim-sulfamethoxazole prophylaxis in acute leukemia. Isolation of resistant plasmids from strains of Enterobacteriaceae are causing bacteremia. N. Engl. J. Med. 306: 16–20.PubMedGoogle Scholar
  73. 73.
    Murray, B.E., Rensimer, E.R., DuPort, H.L., (1982), Emergence of high level trimethoprim, resistance in fecal Escherichia coli during oral administration of trimethoprim-or trimethoprim-sulfamethoxazole. N. Engl. J. Med. 306: 130–135.PubMedGoogle Scholar
  74. 74.
    Bucaneve, G., Micozzi, A., Menichetti, F., Martino, P., Dionisi, M.S., Martirelli G., Allione, B., D'Antonio, D., Buelli, M., Nosari, A.M., Cilloni, D., Zuffa, E., Cantaffa, R., Specchia, G., Amadori, S., Fabbiano, F., Deliliers, G.L., Lauria, F., Foa, R., Del Favero, A., for the Gruppo Italiano Malattié Ematologiche dell &3x25FB; Adulto (GIMEMA) Infection Program, (2005), Levo-floxacin to prevent bacterial infection in patients with cancer and neutropenia. N. Engl. J. Med. 353: 977–987.CrossRefPubMedGoogle Scholar
  75. 75.
    Cullen, M., Steven, N, Billingham, L., Gaunt, C, Hastings, M., Simmonds, P., Stuart, N, Rea, D., Bower, M., Fernando, I., Huddart, R., Gollins, S., Phil, D., Stanley, A., for the Simple Investigation in Neutropenic Individuals of the Frequency of Infection after chemotherapy + / –Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group, (2005), Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N. Engl J. Med. 353: 988– 998.CrossRefPubMedGoogle Scholar
  76. 76.
    Gafter-Gvilli, A., Fraser, A., Paul, M., Leibovici, L., (2005), Meta-Analysis: Antibiotic prophylaxis reduces mortality in neutropenic patients. Ann. Intern. Med. 142: 979–995.Google Scholar
  77. 77.
    Viscoli, C, Varnier, O., Machetti, M., (2005), Infections in patients with febrile neutropenia; epidemiology, microbiology and risk stratification. Clin. Infect. Dis. (Suppl.4): S240–S245.Google Scholar
  78. 78.
    Kern, W.V., Andriof, E., Oethinger, M., Kern, P., Hacker, J., Morre, R., (1994) Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrobial Agents Chemother. 38: 681–687.Google Scholar
  79. 79.
    Hooper, D.C., (2001), Emerging mechanisms of flouroquinolone resistance. Emerg. Infect. Dis. 7: 337–341.CrossRefPubMedGoogle Scholar
  80. 80.
    Sullivan, K.M., Dykewicz, C.A., Longworth, D.L., Boeckh, M., Baden, C.R., Rubin, R.H., Sepkowitz, K.A., Centers for Disease Control and Prevention; Infectious Diseases Society of America, American Society for Blood and Marrow Transplantation Practice Guidelines and beyond, (2001), 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): 392–421.Google Scholar
  81. 81.
    Clark, O.A., Lyman, G.H., Castro, A.A., Clark, L.G., Djulbegovic, B., (2005), Colony-stimulating factors for chemotherapy–induced febrile neutropenia: a meta-analysis of randomized controlled trials. J. Clin. Oncol. 23: 4198–4214.CrossRefPubMedGoogle Scholar
  82. 82.
    Garcia-Carbonero, R., Mayordomo, J.I., Tornamira, M.V., Lopez–Brea, M., Rueda, A., Guillem. V., Arcediano, A., Yubero, A., Ribera, F., Gomez, C, Tres, A., Perez-Garcia, J.L., Lumbreras, C., Hornedo, J., Cortes-Funes, H., Poz-Ares, L., (2001) Granulocyte colony-stimulating factor in treatment of high-risk febrile neutropenia: a multicenter randomized trial. J. National Cancer Inst. 93: 31–38.CrossRefGoogle Scholar
  83. 83.
    Lyman, G., H., Kuderer, N.M., (2004), The economics of the colony – stimulating factors in the prevention and treatment of febrile neutropenia. Crit. Rev. Oncol. Hematol. 50: 129–146.CrossRefPubMedGoogle Scholar
  84. 84.
    Bohlius, R., Reiser, M., Schwarzer G., Engert, A., (2004), Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst. Rev., C.D 003189: PMID: 14974009.Google Scholar
  85. 85.
    Sasse, E.C., Sasse, A.d., Brandalise, S., Clark, O.A., Richards, S., (2005) Colony stimulating factors for prevention of myelosuppressive therapy induced febrile neutropenia in children with acute lymphoblastic leukemia. Cochrane Database Syst. Rev. CD004139.Google Scholar
  86. 86.
    Sung, L., Nathan, P.C., Lange, B., Beyene, J., Buchanan, G.R., (2004), Prophylactic granulocyte colony stimulating factor and granulocyte-macrophage colony-stimulating factor decreases febrile neutropenia after chemotherapy in children with cancer: a meta-analysis of randomized trials. J. Clin. Oncol. 22: 3350–3356.CrossRefPubMedGoogle Scholar
  87. 87.
    Goodman, J.L., Winston, D.J., Greenfield, A., Chandrasekar, P.N., Fox, B., Kaizer, H., Shadduck, R.K., Shea, T.C., Stiff, P., Friedman, D.J., (1992), A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation: a prospective, randomized, double-blind study. N. Engl. J. Med. 326: 845–851.PubMedGoogle Scholar
  88. 88.
    Slavin, M.A., Osborne, B., Adams, R., Levenstein, M.J., Schoch, H.G., Feldman, A.R. Myers, J.D., Bowden, R.A., (1995), Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow-transplantation – a prospective, randomized, double-blind study. J. Infect. Dis. 171: 1545–1552.PubMedGoogle Scholar
  89. 89.
    Ellis, M.E., Clink, H., Ernst, P., Halim, M.A., Padmos, A., Spence, D., Kalin, M., Hussain Qadri, S.M., Burnie, J., Greer, W., (1994) Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur. J. Clin Microbiol. Infect. Dis. 13: 3–11.CrossRefPubMedGoogle Scholar
  90. 90.
    Kanda, Y., Yamamoto, R., Chizuka, A., Hamaki T., Suguro, M., Arai, C., Matsuyama, T., Takezako, N., Miwa, A., Kern, W., Kami, M., Akiyama, H., Hirai, H., Togawa, A. (2000) Prophylactic action of oral fluconazole against fungal infection in neutropenic patients: a meta-analysis of 16 randomized, controlled trials, Cancer: 89 1611–1625.CrossRefPubMedGoogle Scholar
  91. 91.
    Wingard, J.R., Mertz, M.G., Rinaldi, M.G., Johnson, T.R., Karp, J.E., Saral, R., (1991), Increases in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N. Engl. J. Med. 325: 1274–1277.PubMedGoogle Scholar
  92. 92.
    Marr, K.A., Saidel, K., White, T.C., Bowden, R.A., (2000), Candidemia in allogeneic blood and marrow transplant recipients: Evolution of risk factors after the adoption of prophylactic fluconazole. J. Infect. Dis. 181: 309–316.CrossRefPubMedGoogle Scholar
  93. 93.
    Menichetti, F., Del Favero, A., Martino, P., Bucaneve, G., Micozzi, A., Girmenia, C., Barbabietola, G., Pagano, L., Leoni, P., Specchia, G., Caiozzo, A., Raimondi, R., Mandelli, F., and the GIMEMA Infection Program, (1994), Itraconazole oral solution as prophylaxis for fungal infection in neutropenic patients with hematologic malignancies: a randomized, placebo – controlled, double-blind, multicenter trial. Clin. Infect. Dis. 28: 250–255.CrossRefGoogle Scholar
  94. 94.
    Nucci, M., Biasoli, I., Akiti, T., Silveira, F., Solza, C., Barreiros, G., Spector, N., Derossi, A., Pulcheri, W., (2000), A double-blind, randomized, placebo-controlled trial of itraconazole, capsules as antifungal prophylaxis for neutropenic patients. Clin. Infect. Dis. 30: 300–305.CrossRefPubMedGoogle Scholar
  95. 95.
    Winston, D.J., Maziarz, R.T., Chandrasekar, P.H., Lazarus, H.M., Goldman, M., Blumer, J.L. Leitz, G. J., Territo, M.C., (2003), Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hemotopoietic stem-cell transplant recipients. Ann. Intern. Med. 138: 705–713.PubMedGoogle Scholar
  96. 96.
    Vardakas, K.A., Michalopoulos, A., Falagas, M.E., (2005), Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with hematological malignancies: a meta-analysis of randomized-controlled trials. Brit. J. Haematol. 131: 22–28.CrossRefGoogle Scholar
  97. 97.
    Cornely, O.A., Maertens, J., Winston, D. J., Perfect, J., Ullmann, A.J., Helfgott, D., Walsh, T.J., Holowiecki, J., Stockelberg, D., Goh, Y.T., Petrini, M., Hardalo, C., Suresh, R., Angulo-Gonzalez, D., (2007) Posoconazole vs fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 356: 348–359.CrossRefPubMedGoogle Scholar
  98. 98.
    Rijnders, B.J., Cornelissen, J.J., Slobbe, L., Becker, M.J., Doorduijn, J.K., Hop, W.C., Ruijgrok, E.J., Lo¨wenberg, B., Vulto, A., Lugtenburg, P.J., de Marie, S., (2008), Aerolized amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin. Infect. Dis. 46: 1401–1408.CrossRefPubMedGoogle Scholar
  99. 99.
    Imbof, A., Arunmozhi Balajee, A., Fredricks, D.N., Englund, J.A., Marr, K.A., (2004), Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin. Infect. Dis. 39: 743–746.CrossRefGoogle Scholar
  100. 100.
    Mego, M., Ebringer, L., Drgona, L., Mordiak, J., Trupl, J., Greksak, R., Nemova, I., Oravcova, E., Zajac, V., Koza, I., (2005), Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Pilot study phase I. Neoplasma; 52: 159–164.PubMedGoogle Scholar
  101. 101.
    Donnelly, J.P., (2006), Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin. Infect. Dis. 42: 487–489.CrossRefPubMedGoogle Scholar
  102. 102.
    Pamer EG., 2008, TLR polymorphisms and the risk of invasive fungal infections (Editorial). N. Engl. J. Med. 359: 1836–1838.CrossRefPubMedGoogle Scholar
  103. 103.
    Bochud, P.Y., Chien, J.W., Marr, K.A., Leisenring, W.M., Upton, A., Janer, M., Rodrigues, S. D., Li, S., Hansen, J.A., Zhao, L.P., Aderem, A., Boeckh, (2008), Toll-like receptor 4 polymorphism and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 359: 1766–1777.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Personalised recommendations