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The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea

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Abstract

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5–7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

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Acknowledgments

This work was supported in part by a grant from Janssen Korea, Seoul, South Korea. We thank all the nurses and doctors who were involved in caring for the patients.

Conflict of interest

The authors declare that they have no other conflict of interest besides receiving the grant.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Jin Seok Kim, June-Won Cheong & Yoo Hong Min

  2. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, South Korea

    Yeo-Kyeoung Kim

  3. Departments of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea

    Jinny Park

  4. Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea

    Yeung-Chul Mun

  5. Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea

    Hye Jin Kang

  6. Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea

    Hyeon Gyu Yi

  7. Department of Hematology, Asan Medical Center,University of Ulsan College of Medicine, Seoul, South Korea

    Je-Hwan Lee

  8. Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea

    Yang Soo Kim

  9. Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea

    Hun-Mo Ryoo

  10. Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea

    Sung-Hyun Kim

  11. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea

    Ho Young Kim

  12. Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea

    Jin Young Kim

  13. Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea

    Dong-Gun Lee

  14. Department of Internal Medicine, Gyeongsang National University, Jinju, South Korea

    Hoon-Gu Kim

  15. Division of Hematology and Hematological Malignancies, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

    Hawk Kim

  16. Department of Internal medicine, Inje University Haeundae Paik Hospital, 875 Haeundae-ro, Haeundae-gu, Busan, 612-896, South Korea

    Young-Don Joo

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  1. Jin Seok Kim
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Correspondence to Young-Don Joo or Yoo Hong Min.

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Kim, J.S., Cheong, JW., Kim, YK. et al. The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea. Ann Hematol 93, 33–42 (2014). https://doi.org/10.1007/s00277-013-1826-x

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  • DOI: https://doi.org/10.1007/s00277-013-1826-x

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