title: Clinical efficacy and safety of arbekacin sulfate in patients with MRSA sepsis or pneumonia: a multi-institutional study.
abstract: Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration (C (peak)) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C (peak) was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C (peak) were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C (peak) at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy.
authors.affiliation: Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan. tetsuya@tokyo-med.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hanaki
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kimura
authors.forename: Manabu
authors.initials: M
authors.lastname: Nemoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokota
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
authors.forename: Nobu
authors.initials: N
authors.lastname: Akiyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyao
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yukioka
authors.forename: Kazui
authors.initials: K
authors.lastname: Soma
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Takao
authors.initials: T
authors.lastname: Arai
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ikegami
authors.forename: Toshio
authors.initials: T
authors.lastname: Ichiwata
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Totsuka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sunakawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003982:Dibekacin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008875:Middle Aged; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D003982:Dibekacin; C031986:arbekacin