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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

  • Kim, Jin Seok ( Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea) , Min, Yoo Hong (Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea) , Kim, Yeo-Kyeoung ( Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, South Korea) , Park, Jinny (Departments of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea) , Mun, Yeung-Chul (문영철, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea) , Kang, Hye Jin (Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea) , Yi, Hyeon Gyu (Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea) , Lee, Je-Hwan (Department of Hematology, Asan Medical Center,University of Ulsan College of Medicine, Seoul, South Korea) , Kim, Yang Soo (Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea) , Ryoo, Hun-Mo ( Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea) , , , , , , , ,
  • ANNALS OF HEMATOLOGY[0939-5555], 2014, v.93 no.1, 33-42

초록/요약

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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