Skip to main content

Advertisement

SpringerLink
Log in

Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, −5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2000;6:659–713; 5; 7–27; quiz 29–33.

    Google Scholar 

  2. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326:845–51.

    Article  CAS  PubMed  Google Scholar 

  3. Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis. 1995;171:1545–52.

    Article  CAS  PubMed  Google Scholar 

  4. van Burik JH, Leisenring W, Myerson D, Hackman RC, Shulman HM, Sale GE, et al. The effect of prophylactic fluconazole on the clinical spectrum of fungal diseases in bone marrow transplant recipients with special attention to hepatic candidiasis. An autopsy study of 355 patients. Medicine (Baltimore). 1998;77:246–54. doi:10.1097/00005792-199807000-00003.

    Article  Google Scholar 

  5. Hovi L, Saarinen-Pihkala UM, Vettenranta K, Saxen H. Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years. Bone Marrow Transplant. 2000;26:999–1004. doi:10.1038/sj.bmt.1702654.

    Article  CAS  PubMed  Google Scholar 

  6. Walsh TJ. Echinocandins—an advance in the primary treatment of invasive candidiasis. N Engl J Med. 2002;347:2070–2. doi:10.1056/NEJMe020142.

    Article  PubMed  Google Scholar 

  7. Georgopapadakou NH. Update on antifungals targeted to the cell wall: focus on beta-1, 3-glucan synthase inhibitors. Expert Opin Invest Drugs. 2001;10:269–80. doi:10.1517/13543784.10.2.269.

    Article  CAS  Google Scholar 

  8. Petraitis V, Petraitiene R, Groll AH, Roussillon K, Hemmings M, Lyman CA, et al. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2002;46:1857–69. doi:10.1128/AAC.46.6.1857-1869.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. van Burik JA, Ratanatharathorn V, Stepan DE, Miller CB, Lipton JH, Vesole DH, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. 2004;39:1407–16. doi:10.1086/422312.

    Article  PubMed  Google Scholar 

  10. Hashino S, Morita L, Takahata M, Onozawa M, Nakagawa M, Kawamura T, et al. Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation. Int J Hematol. 2008;87:91–7. doi:10.1007/s12185-007-0011-1.

    Article  PubMed  Google Scholar 

  11. de Wet N, Llanos-Cuentas A, Suleiman J, Baraldi E, Krantz EF, Della Negra M, et al. A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients. Clin Infect Dis. 2004;39:842–9. doi:10.1086/423377.

    Article  PubMed  Google Scholar 

  12. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14. doi:10.1086/323335.

    Article  CAS  PubMed  Google Scholar 

  13. de Wet NT, Bester AJ, Viljoen JJ, Filho F, Suleiman JM, Ticona E, et al. A randomized, double blind, comparative trial of micafungin (FK463) vs. fluconazole for the treatment of oesophageal candidiasis. Aliment Pharmacol Ther. 2005;21:899–907. doi:10.1111/j.1365-2036.2005.02427.x.

    Article  PubMed  Google Scholar 

  14. Pettengell K, Mynhardt J, Kluyts T, Lau W, Facklam D, Buell D. Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent. Aliment Pharmacol Ther. 2004;20:475–81. doi:10.1111/j.1365-2036.2004.02083.x.

    Article  CAS  PubMed  Google Scholar 

  15. Hatano K, Morishita Y, Nakai T, Ikeda F. Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus. J Antibiot (Tokyo). 2002;55:219–22.

    Article  CAS  Google Scholar 

  16. Nakai T, Uno J, Otomo K, Ikeda F, Tawara S, Goto T, et al. In vitro activity of FK463, a novel lipopeptide antifungal agent, against a variety of clinically important molds. Chemotherapy. 2002;48:78–81. doi:10.1159/000057666.

    Article  CAS  PubMed  Google Scholar 

  17. Sirohi B, Powles RL, Chopra R, Russell N, Byrne JL, Prentice HG, et al. A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation. Bone Marrow Transplant. 2006;38:47–51. doi:10.1038/sj.bmt.1705398.

    Article  CAS  PubMed  Google Scholar 

  18. Saad AH, DePestel DD, Carver PL. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants. Pharmacotherapy. 2006;26:1730–44. doi:10.1592/phco.26.12.1730.

    Article  CAS  PubMed  Google Scholar 

  19. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, et al. Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005;57:759–64. doi:10.1211/0022357056118.

    Article  CAS  PubMed  Google Scholar 

  20. Hebert MF, Blough DK, Townsend RW, Allison M, Buell D, Keirns J, et al. Concomitant tacrolimus and micafungin pharmacokinetics in healthy volunteers. J Clin Pharmacol. 2005;45:1018–24. doi:10.1177/0091270005279274.

    Article  CAS  PubMed  Google Scholar 

  21. Tawara S, Ikeda F, Maki K, Morishita Y, Otomo K, Teratani N, et al. In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi. Antimicrob Agents Chemother. 2000;44:57–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Matsue K, Uryu H, Koseki M, Asada N, Takeuchi M. Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. Clin Infect Dis. 2006;42:753–7. doi:10.1086/500323.

    Article  CAS  PubMed  Google Scholar 

  23. Goodman D, Pamer E, Jakubowski A, Morris C, Sepkowitz K. Breakthrough trichosporonosis in a bone marrow transplant recipient receiving caspofungin acetate. Clin Infect Dis. 2002;35:E35–6. doi:10.1086/341305.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Okayama, Japan

    Yasushi Hiramatsu, Yoshinobu Maeda, Nobuharu Fujii, Ken-ichi Matsuoka, Katsuji Shinagawa, Kazuma Ikeda & Mitsune Tanimoto

  2. Department of Infection Control and Prevention, Kyoto University Hospital, Kyoto, Japan

    Takashi Saito

  3. Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan

    Yuichiro Nawa & Masamichi Hara

  4. Department of Hematology, Okayama Rousai Hospital, Okayama, Japan

    Tomofumi Yano

  5. Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Shoji Asakura & Kazutaka Sunami

  6. Department of Internal Medicine, Chugoku Central Hospital, Hiroshima, Japan

    Takayuki Tabayashi & Akira Miyata

  7. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Nagoya, Japan

    Keitaro Matsuo

  8. Department of Internal Medicine, Okayama University, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan

    Mitsune Tanimoto

Authors
  1. Yasushi Hiramatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshinobu Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nobuharu Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichiro Nawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masamichi Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomofumi Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shoji Asakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazutaka Sunami
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takayuki Tabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Akira Miyata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ken-ichi Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Katsuji Shinagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kazuma Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Keitaro Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mitsune Tanimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the West-Japan Hematology and Oncology Group (West-JHOG)

Corresponding author

Correspondence to Mitsune Tanimoto.

About this article

Cite this article

Hiramatsu, Y., Maeda, Y., Fujii, N. et al. Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation. Int J Hematol 88, 588–595 (2008). https://doi.org/10.1007/s12185-008-0196-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-008-0196-y

Keywords

Search

Navigation