Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections.
We performed high-dose loading (12 mg/kg every 12 h for 48 h; 4 doses total) of teicoplanin (TEIC) in patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections, with the goal of achieving target serum concentration (TEICc) ≥ 15 mg/l within 48 h of starting administration. The safety and effectiveness of the fixed, early-stage administration method were evaluated across a range of kidney dysfunction severity levels. TEIC high-dose loading was administered to 106 patients with MRSA infection from February 2010 to February 2013. After high-dose loading, maintenance doses based on therapeutic drug monitoring (TDM) of TEICc were administered via 30-min intravenous drips, every 24 h. Subjects were divided into 4 groups based on kidney function and renal replacement therapy (RRT) status for safety and effectiveness evaluation: group 1 (G1) did not undergo RRT and exhibited creatinine clearance (Ccr; ml/min/m(2)) >50, group 2 (G2) exhibited Ccr ≤ 50, group 3 (G3) underwent continuous RRT (CRRT), and group 4 (G4) underwent intermittent RRT (IRRT). TEICc was measured after 24, 48, 72, and 144 h, immediately before TEIC administration. Target TEICc was reached in all groups, and bacteriological effectiveness and utility were high in G1, G2, and G3. The maximum TEICc (≥ 28.0 mg/l) and serum albumin (≤ 1.84 g/dl) were associated with organ toxicity. Fixed high-dose loading of TEIC achieved the target therapeutic range (≥ 15 mg/l) within 48 h of the start of administration regardless of kidney dysfunction, and exhibited sufficient utility.
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan. Electronic address: nakamura_atsuo@med.kurume-u.ac.jp.
Atsuo
A
Nakamura
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Osamu
O
Takasu
Department of Pharmacy, Kurume University Hospital, Japan.
Yoshiro
Y
Sakai
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Teruo
T
Sakamoto
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Norio
N
Yamashita
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Shinjiro
S
Mori
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Toshio
T
Morita
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Masakazu
M
Nabeta
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Nobuhisa
N
Hirayu
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Naomasa
N
Yoshiyama
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Mariko
M
Moroki
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Keita
K
Tashiro
Department of Trauma and Critical Care Medicine, Kurume University School of Medicine, Japan.
Mikinori
M
Kannae
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008875:Middle Aged; D011446:Prospective Studies; D012709:Serum Albumin / Q000378:metabolism; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy*; D017334:Teicoplanin / Q000008:administration & dosage* / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D012709:Serum Albumin; D017334:Teicoplanin
High-dose loading; Hypoalbuminemia; MRSA; Teicoplanin