title: Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.
abstract: We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: June-Won
authors.initials: JW
authors.lastname: Cheong
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
authors.affiliation: Department of Hematology/Oncology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dong-Gun
authors.initials: DG
authors.lastname: Lee
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University, Busan, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Hoon-Gu
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University Medical Center, Seoul, Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, Korea.
authors.forename: Hun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea.
authors.forename: In Sung
authors.initials: IS
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Yeung Chul
authors.initials: YC
authors.lastname: Mun
authors.affiliation: Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea.
authors.forename: Deog-Yeon
authors.initials: DY
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Byeong-Bae
authors.initials: BB
authors.lastname: Park
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D058888:14-alpha Demethylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy; D003047:Coccidioidomycosis / Q000150:complications / Q000188:drug therapy; D064147:Febrile Neutropenia / Q000150:complications / Q000188:drug therapy; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D017964:Itraconazole / Q000009:adverse effects / Q000627:therapeutic use; D008351:Mannans / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; C012990:galactomannan; D005690:Galactose; D017964:Itraconazole; D008351:Mannans
keywords: Empirical Antifungal Therapy; Galactomannan Test; Hematological Malignancy; Itraconazole