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 ( Cpeak ) of ABK has not yet been fully in...

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Published in:Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2013-02, Vol.19 (1), p.128-137
Main Authors: Matsumoto, Tetsuya, Hanaki, Hideaki, Kimura, Toshimi, Nemoto, Manabu, Higashihara, Masaaki, Yokota, Hiroyuki, Oda, Shigeto, Akiyama, Nobu, Miyao, Naoki, Yoshida, Minoru, Yukioka, Tetsuo, Soma, Kazui, Ohyashiki, Kazuma, Suzuki, Yukio, Arai, Takao, Ikegami, Keiichi, Ichiwata, Toshio, Otsuka, Yoshihito, Kobayashi, Masahiro, Totsuka, Kyoichi, Sunakawa, Keisuke
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Anti-Infective Agents - administration & dosage
Anti-Infective Agents - adverse effects
Anti-Infective Agents - pharmacokinetics
Anti-Infective Agents - therapeutic use
Dibekacin - administration & dosage
Dibekacin - adverse effects
Dibekacin - analogs & derivatives
Dibekacin - pharmacokinetics
Dibekacin - therapeutic use
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Monitoring
Female
Hematology, Oncology and Palliative Medicine
Humans
Infectious Diseases
Japan
Male
Medical Microbiology
Medicine
Medicine & Public Health
Methicillin-Resistant Staphylococcus aureus - drug effects
Middle Aged
Original Article
Pneumonia, Staphylococcal - drug therapy
Pneumonia, Staphylococcal - microbiology
Sepsis - drug therapy
Sepsis - microbiology
Staphylococcus aureus
Virology
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Summary: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 ( Cpeak ) 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 Cpeak 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 Cpeak 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 Cpeak 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.
ISSN:1341-321X
1437-7780
DOI:10.1007/s10156-012-0519-z