title: Clinical efficacy and safety of arbekacin for high-risk infections in patients with hematological malignancies.
abstract: We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan. miura.katsuhiro@nihon-u.ac.jp.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Miura
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Uchino
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kodaira
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Iriyama
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakagami
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hojo
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurita
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Kusuda
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirabayashi
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan. hatta.yoshihiro@nihon-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Takei
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003982:Dibekacin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D064147:Febrile Neutropenia / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000209:etiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D047090:beta-Lactams; D003982:Dibekacin; C031986:arbekacin
keywords: Arbekacin; Coagulase-negative Staphylococci; Febrile neutropenia; Methicillin-resistant Staphylococcus aureus; Therapeutic drug monitoring; Vancomycin