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Efficacy and safety of antifungal prophylaxis with oral itraconazole solution among patients receiving corticosteroids: who should be given prophylaxis?

Abstract

The incidence of systemic fungal infections has risen, as shown by increases in the numbers of immunosuppressed or immunocompromised patients. The consequences of these fungal infections are occasionally serious. However, the efficacy of antifungal prophylaxis in patients receiving corticosteroid treatment has not been well investigated, even though they are susceptible to severe fungal infections. Therefore, we retrospectively evaluated the prophylactic efficacy of an antifungal agent—oral itraconazole solution (ITCZ-OS)—for immunosuppressed patients receiving corticosteroids in a single institution. Of 39 patients, 18 received prophylaxis with ITCZ-OS at a dose of 200 mg/day, and 21 did not. As a result, no fungal infections developed in the prophylactic group, but 7 of the 21 patients (33%) in the non-prophylactic group suffered from fungal infections consisting of 3 non-invasive candidiases, 2 invasive candidiases, and 2 invasive pulmonary aspergilloses. Among the non-prophylactic group, aging and hypoalbuminemia were statistically significantly associated with incidence of invasive fungal infections. Of the four patients with invasive fungal infections, three had concomitant chronic illness such as diabetes. Toxicity among the prophylactic group was not statistically significantly different from that of the non-prophylactic group. In addition, none needed discontinuation of the drug. These results indicate the potential antifungal prophylactic effect of ITCZ-OS for a subset of patients treated with moderate or high doses of corticosteroids.

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References

  1. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362:1828–38.

    PubMed  Article  CAS  Google Scholar 

  2. Hennig S, Waterhouse TH, Bell SC, France M, Wainwright CE, Miller H, et al. A d-optimal designed population pharmacokinetic study of oral itraconazole in adult cystic fibrosis patients. Br J Clin Pharmacol. 2007;63:438–50.

    PubMed  Article  CAS  Google Scholar 

  3. Johnson MD, Hamilton CD, Drew RH, Sanders LL, Pennick GJ, Perfect JR. A randomized comparative study to determine the effect of omeprazole on the peak serum concentration of itraconazole oral solution. J Antimicrob Chemother. 2003;51:453–7.

    PubMed  Article  CAS  Google Scholar 

  4. Kageyama S, Masuya M, Tanaka I, Oka K, Morita K, Tamaki S, et al. Plasma concentration of itraconazole and its antifungal prophylactic efficacy in patients with neutropenia after chemotherapy for acute leukemia. J Infect Chemother. 1999;5:213–6.

    PubMed  Article  CAS  Google Scholar 

  5. Glasmacher A, Prentice A, Gorschluter M, Engelhart S, Hahn C, Djulbegovic B, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol. 2003;21:4615–26.

    PubMed  Article  CAS  Google Scholar 

  6. Robenshtok E, Gafter-Gvili A, Goldberg E, Weinberger M, Yeshurun M, Leibovici L, et al. Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2007;25:5471–89.

    PubMed  Article  CAS  Google Scholar 

  7. Goldberg E, Gafter-Gvili A, Robenshtok E, Leibovici L, Paul M. Empirical antifungal therapy for patients with neutropenia and persistent fever: systematic review and meta-analysis. Eur J Cancer. 2008;44:2192–203.

    PubMed  Article  CAS  Google Scholar 

  8. Kaptan K, Ural AU, Cetin T, Avcu F, Beyan C, Yalcin A. Itraconazole is not effective for the prophylaxis of fungal infections in patients with neutropenia. J Infect Chemother. 2003;9:40–5.

    PubMed  Article  CAS  Google Scholar 

  9. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.

    PubMed  Article  Google Scholar 

  10. Van Campenhout H, Marbaix S, Derde MP, Annemans L. Voriconazole treatment of invasive aspergillosis: real-world versus health-economic model results. Clin Drug Investig. 2008;28:509–21.

    PubMed  Article  Google Scholar 

  11. Glasmacher A, Hahn C, Molitor E, Marklein G, Sauerbruch T, Schmidt-Wolf IG. Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules. Mycoses. 1999;42:591–600.

    PubMed  Article  CAS  Google Scholar 

  12. Richardson M, Lass-Florl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect. 2008;14(Suppl 4):5–24.

    PubMed  Article  Google Scholar 

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Acknowledgments

This study was not supported by any funds. The authors would like to thank Satoshi Yamaguchi, Yuki Nishiumi, and Jun Yamamoto (Janssen Pharmaceutical K. K.) for offering sufficient information about fungal infections.

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Correspondence to Katsuhiro Miura.

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Iriyama, N., Matsukawa, Y., Miura, K. et al. Efficacy and safety of antifungal prophylaxis with oral itraconazole solution among patients receiving corticosteroids: who should be given prophylaxis?. J Infect Chemother 17, 744–749 (2011). https://doi.org/10.1007/s10156-011-0251-0

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  • DOI: https://doi.org/10.1007/s10156-011-0251-0

Keywords

  • Corticosteroid
  • Fungal infection
  • Itraconazole
  • Prophylaxis