High-dose regimen to achieve novel target trough concentration in teicoplanin.
In the treatment of severe MRSA infections such as endocarditis, more than 20 mg/L of plasma trough concentration (C(min)) is recommended for teicoplanin; however, in the treatment of common MRSA infections, recommended C(min) remains more than 10 mg/L. In this study, we set C(min) as 15-30 mg/L to obtain a favorable clinical outcome in the treatment of common MRSA infections, and investigated the optimal loading regimen that achieved the target C(min) in patients with normal renal function. Seventy-eight patients received the high-dose regimen A (6 mg/kg every 12-h for initial two days) and 60 patients received the high-dose regimen B (the first five loading doses of 10-12 mg/kg at 12-h intervals for initial three days, followed by 6 mg/kg once daily). The mean C(min) on the 4th day was 13.7 ± 5.3 mg/L in regimen A, and 20.0 ± 6.6 mg/L in regimen B (P < 0.001), and the proportion of patients achieving the 15-30 mg/L was 25.6% and 68.3% (P < 0.001). Clinical response at end-of treatment were 66.7% and 85.0% (P = 0.014). The patients of initial C(min) with ≥15 mg/L had tended to be higher clinical response than those with <15 mg/L (80.9% vs 68.6%, P = 0.084). There were no significant differences in the occurrence of adverse effects in regimen A and B (nephrotoxicity; 1.3% vs 3.3%, P = 0.413, hepatotoxicity; 5.1% vs 3.3%, P = 0.608). In conclusion, to obtain C(min) 15-30 mg/L, the first five loading doses of 10-12 mg/kg at 12-h intervals was required in patients with normal renal function.
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address: taka76@hyo-med.ac.jp.
Takashi
T
Ueda
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshio
Y
Takesue
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Kazuhiko
K
Nakajima
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Kaoru
K
Ichki
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Yasunao
Y
Wada
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Miyuki
M
Komatsu
Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.
Toshie
T
Tsuchida
Department of Pharmacy, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshiko
Y
Takahashi
Department of Pharmacy, Hyogo College of Medicine, Nishinomiya, Japan.
Mika
M
Ishihara
Department of Pharmacy, Hyogo College of Medicine, Nishinomiya, Japan.
Takeshi
T
Kimura
Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Motoi
M
Uchino
Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Hiroki
H
Ikeuchi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism; D017334:Teicoplanin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017334:Teicoplanin
Loading dose; TDM; Teicoplanin; Trough concentration