Table of Contents Author Guidelines Submit a Manuscript
Advances in Hematology
Volume 2014 (2014), Article ID 986938, 9 pages
http://dx.doi.org/10.1155/2014/986938
Review Article

Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

1Hospital Universitario Torrejón de Ardoz, Servicio de Hematología, Calle Mateo Inurria, 28850 Madrid, Spain
2Hospital Universitario Fundación Alcorcón, Servicio de Hematología, Calle Budapest 1, 28922 Madrid, Spain
3Unidad de Medicina Interna, Sección de Enfermedades Infecciosas, Hospital Universitario Fundación Alcorcón, Calle Budapest 1, 28922 Madrid, Spain

Received 30 July 2014; Revised 18 October 2014; Accepted 3 November 2014; Published 27 November 2014

Academic Editor: Myriam Labopin

Copyright © 2014 Paola Villafuerte-Gutierrez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. G. Freifeld, E. J. Bow, K. A. Sepkowitz et al., “Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america,” Clinical Infectious Diseases, vol. 52, no. 4, pp. e56–e93, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. M. K. Keng and M. A. Sekeres, “Febrile neutropenia in hematologic malignancies,” Current Hematologic Malignancy Reports, vol. 8, no. 4, pp. 370–378, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Goulenok and B. Fantin, “Antimicrobial treatment of febrile neutropenia: pharmacokinetic-pharmacodynamic considerations,” Clinical Pharmacokinetics, vol. 52, no. 10, pp. 869–883, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Pagano, M. Caira, G. Rossi et al., “A prospective survey of febrile events in hematological malignancies,” Annals of Hematology, vol. 91, no. 5, pp. 767–774, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. J. de Naurois, I. Novitzky-Basso, M. J. Gill, F. M. Marti, M. H. Cullen, and F. Roila, “Management of febrile neutropenia: ESMO Clinical Practice Guidelines,” Annals of Oncology, vol. 21, no. 5, pp. v252–v256, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. C. R. Flowers, J. Seidenfeld, E. J. Bow et al., “Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American society of clinical oncology clinical practice guideline,” Journal of Clinical Oncology, vol. 31, no. 6, pp. 794–810, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. L. R. Baden, W. Bensinger, M. Angarone et al., “Prevention and treatment of cancer-related infections,” Journal of the National Comprehensive Cancer Network, vol. 10, no. 11, pp. 1412–1445, 2012. View at Google Scholar · View at Scopus
  8. J. Klastersky, M. Paesmans, E. B. Rubenstein et al., “The multinational association for supportive care in cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients,” Journal of Clinical Oncology, vol. 18, no. 16, pp. 3038–3051, 2000. View at Google Scholar · View at Scopus
  9. E. J. Bow, “Management of the febrile neutropenic cancer patient: lessons from 40 years of study,” Clinical Microbiology and Infection, Supplement, vol. 11, no. 5, pp. 24–29, 2005. View at Google Scholar · View at Scopus
  10. G. Bucaneve, A. Micozzi, F. Menichetti et al., “Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia,” The New England Journal of Medicine, vol. 353, no. 10, pp. 977–987, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. M. A. Slavin, S. Lingaratnam, L. Mileshkin et al., “Use of antibacterial prophylaxis for patients with neutropenia,” Internal Medicine Journal, vol. 41, no. 1, pp. 102–109, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Leibovici, M. Paul, M. Cullen et al., “Antibiotic prophylaxis in neutropenic patients: new evidence, practical decisions,” Cancer, vol. 107, no. 8, pp. 1743–1751, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Gafter-Gvili, A. Fraser, M. Paul, and L. Leibovici, “Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients,” Annals of Internal Medicine, vol. 142, no. 12 I, pp. 979–995, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Gafter-Gvili, A. Fraser, M. Paul, M. van de Wetering, L. Kremer, and L. Leibovici, “Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy,” The Cochrane Database of Systematic Reviews, vol. 1, Article ID CD004386, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. J. J. Vehreschild, G. Moritz, M. J. G. T. Vehreschild et al., “Efficacy and safety of moxifloxacin as antibacterial prophylaxis for patients receiving autologous haematopoietic stem cell transplantation: a randomised trial,” International Journal of Antimicrobial Agents, vol. 39, no. 2, pp. 130–134, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. F. G. De Rosa, I. Motta, E. Audisio et al., “Epidemiology of bloodstream infections in patients with acute myeloid leukemia undergoing levofloxacin prophylaxis,” BMC Infectious Diseases, vol. 13, no. 1, article 563, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. E. J. Bow, “Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients,” Current Opinion in Infectious Diseases, vol. 24, no. 6, pp. 545–553, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Kjellander, M. Björkholm, H. Cherif, M. Kalin, and C. G. Giske, “Hematological: low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study,” European Journal of Haematology, vol. 88, no. 5, pp. 422–430, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Chong, H. Yakushiji, Y. Ito, and T. Kamimura, “Clinical impact of fluoroquinolone prophylaxis in neutropenic patients with hematological malignancies,” International Journal of Infectious Diseases, vol. 15, no. 4, pp. e277–e281, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. E. M. Trecarichi and M. Tumbarello, “Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact,” Current Opinion in Infectious Diseases, vol. 27, no. 2, pp. 200–210, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. L. Pagano, M. Caira, A. Candoni et al., “The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study,” Haematologica, vol. 91, no. 8, pp. 1068–1075, 2006. View at Google Scholar · View at Scopus
  22. E. Robenshtok, A. Gafter-Gvili, E. Goldberg et al., “Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis,” Journal of Clinical Oncology, vol. 25, no. 34, pp. 5471–5489, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. E. J. Bow, M. Laverdière, N. Lussier, C. Rotstein, M. S. Cheang, and S. Ioannou, “Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta-analysis of randomized-controlled clinical trials,” Cancer, vol. 94, no. 12, pp. 3230–3246, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. O. A. Cornely, J. Maertens, D. J. Winston et al., “Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia,” The New England Journal of Medicine, vol. 356, no. 4, pp. 348–359, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. A. J. Ullmann, J. H. Lipton, D. H. Vesole et al., “Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease,” The New England Journal of Medicine, vol. 356, no. 4, pp. 335–347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. R. Hachem, H. Hanna, D. Kontoyiannis, Y. Jiang, and I. Raad, “The changing epidemiology of invasive candidiasis: candida glabrata and candida krusei as the leading causes of candidemia in hematologic malignancy,” Cancer, vol. 112, no. 11, pp. 2493–2499, 2008. View at Google Scholar · View at Scopus
  27. J.-A. H. van Burik, V. Ratanatharathorn, D. E. Stepan et al., “Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation,” Clinical Infectious Diseases, vol. 39, no. 10, pp. 1407–1416, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. J. R. Wingard, S. L. Carter, T. J. Walsh et al., “Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation,” Blood, vol. 116, no. 24, pp. 5111–5118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. D. I. Marks, A. Pagliuca, C. C. Kibbler et al., “Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation,” British Journal of Haematology, vol. 155, no. 3, pp. 318–327, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. K. A. Marr, F. Crippa, W. Leisenring et al., “Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants,” Blood, vol. 103, no. 4, pp. 1527–1533, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. D. J. Winston, R. T. Maziarz, P. H. Chandrasekar et al., “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,” Annals of Internal Medicine, vol. 138, no. 9, pp. 705–713, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. A. Glasmacher, A. Prentice, M. Gorschlüter et al., “Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients,” Journal of Clinical Oncology, vol. 21, no. 24, pp. 4615–4626, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. K. A. Marr, M. Laverdiere, A. Gugel, and W. Leisenring, “Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay,” Clinical Infectious Diseases, vol. 40, no. 12, pp. 1762–1769, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Cordonnier, C. Robin, A. Alanio, and S. Bretagne, “Antifungal pre-emptive strategy for high-risk neutropenic patients: why the story is still ongoing,” Clinical Microbiology and Infection, vol. 20, supplement 6, pp. 27–35, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Link, A. Böhme, O. A. Cornely et al., “Antimicrobial therapy of unexplained fever in neutropenic patients–guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society),” Annals of Hematology, vol. 82, supplement 2, pp. S105–S117, 2003. View at Google Scholar
  36. K. V. I. Rolston, “Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia,” Clinical Infectious Diseases, vol. 40, no. 4, pp. S246–S252, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Klastersky, “Concept of empiric therapy with antibiotic combinations. Indications and limits,” The American Journal of Medicine, vol. 80, no. 5, pp. 2–12, 1986. View at Google Scholar · View at Scopus
  38. M. Paul, D. Yahav, A. Bivas, A. Fraser, and L. Leibovici, “Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta-lactams,” Cochrane Database of Systematic Reviews, vol. 11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Gea-Banacloche, “Evidence-based approach to treatment of febrile neutropenia in hematologic malignancies,” Hematology/the Education Program of the American Society of Hematology, vol. 2013, no. 1, pp. 414–422, 2013. View at Publisher · View at Google Scholar
  40. M. Paul, Y. Dickstein, A. Schlesinger, S. Grozinsky-Glasberg, K. Soares-Weiser, and L. Leibovici, “Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia,” The Cochrane Database of Systematic Reviews, vol. 6, Article ID CD003038, 2013. View at Google Scholar · View at Scopus
  41. W. V. Kern, O. Marchetti, L. Drgona et al., “Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy—EORTC infectious diseases group trial XV,” Journal of Clinical Oncology, vol. 31, no. 9, pp. 1149–1156, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. D. Averbuch, C. Cordonnier, D. M. Livermore et al., “Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European conference on Infections in Leukemia (ECIL-4, 2011),” Haematologica, vol. 98, no. 12, pp. 1836–1847, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. R. S. Stein, J. Kayser, and J. M. Flexner, “Clinical value of empirical amphotericin B in patients with acute myelogenous leukemia,” Cancer, vol. 50, no. 11, pp. 2247–2251, 1982. View at Publisher · View at Google Scholar · View at Scopus
  44. P. A. Pizzo, K. J. Robichaud, F. Gill, and F. G. Witebsky, “Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia,” The American Journal of Medicine, vol. 72, no. 1, pp. 101–111, 1982. View at Publisher · View at Google Scholar · View at Scopus
  45. F. Meunier, “Empirical antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group,” The American Journal of Medicine, vol. 86, no. 6, pp. 668–672, 1989. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Aguilar-Guisado, I. Espigado, E. Cordero et al., “Empirical antifungal therapy in selected patients with persistent febrile neutropenia,” Bone Marrow Transplantation, vol. 45, no. 1, pp. 159–164, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. J. R. Wingard and H. L. Leather, “Empiric antifungal therapy for the neutropenic patient,” Oncology, vol. 15, no. 3, pp. 351–363, 2001. View at Google Scholar · View at Scopus
  48. T. J. Walsh, R. W. Finberg, C. Arndt et al., “Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia,” The New England Journal of Medicine, vol. 340, no. 10, pp. 764–771, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. T. J. Walsh, H. Teppler, G. R. Donowitz et al., “Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia,” The New England Journal of Medicine, vol. 351, no. 14, pp. 1391–1402, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. T. J. Walsh, P. Pappas, D. J. Winston et al., “Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever,” The New England Journal of Medicine, vol. 346, no. 4, pp. 225–234, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Madureira, A. Bergeron, C. Lacroix et al., “Breakthrough invasive aspergillosis in allogeneic haematopoietic stem cell transplant recipients treated with caspofungin,” International Journal of Antimicrobial Agents, vol. 30, no. 6, pp. 551–554, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. B. H. Segal, N. G. Almyroudis, M. Battiwalla et al., “Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts,” Clinical Infectious Diseases, vol. 44, no. 3, pp. 402–409, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Cherif, M. Kalin, and M. Björkholm, “Antifungal therapy in patients with hematological malignancies: how to avoid overtreatment?” European Journal of Haematology, vol. 77, no. 4, pp. 288–292, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Maertens, K. Theunissen, G. Verhoef et al., “Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study,” Clinical Infectious Diseases, vol. 41, no. 9, pp. 1242–1250, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. C. Cordonnier, C. Pautas, S. Maury et al., “Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial,” Clinical Infectious Diseases, vol. 48, no. 8, pp. 1042–1051, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. C. Girmenia, A. Micozzi, G. Gentile et al., “Clinically driven diagnostic antifungal approach in neutropenic patients: a prospective feasibility study,” Journal of Clinical Oncology, vol. 28, no. 4, pp. 667–674, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. L. Pagano, M. Caira, A. Nosari et al., “The use and efficacy of empirical versus pre-emptive therapy in the management of fungal infections: the HEMA e-Chart project,” Haematologica, vol. 96, no. 9, pp. 1366–1370, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. C. O. Morrissey, S. C.-A. Chen, T. C. Sorrell et al., “Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial,” The Lancet Infectious Diseases, vol. 13, no. 6, pp. 519–528, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Hanna, C. Afif, B. Alakech et al., “Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse,” Infection Control and Hospital Epidemiology, vol. 25, no. 8, pp. 646–649, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. I. Raad, H. Hanna, M. Boktour et al., “Management of central venous catheters in patients with cancer and candidemia,” Clinical Infectious Diseases, vol. 38, no. 8, pp. 1119–1127, 2004. View at Google Scholar
  61. G. El Helou, R. Hachem, G. M. Viola et al., “Management of rapidly growing mycobacterial bacteremia in cancer patients,” Clinical Infectious Diseases, vol. 56, no. 6, pp. 843–846, 2013. View at Publisher · View at Google Scholar · View at Scopus