Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days
Takashi Ueda, Yoshio Takesue, Kazuhiko Nakajima, Kaoru Ichiki, Kaori Ishikawa, Y. Takai, Kumiko Yamada, Toshie Tsuchida, Naruhito Otani, Yoshiko Takahashi, Mika Ishihara, Shingo Takubo, Hiroki Ikeuchi, Motoi Uchino, Takeshi Kimura
Abstract
Abstract Background A trough concentration (C min ) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target C min has not been obtained. Even though the recommended high C min of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging. Methods Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The C min was obtained at 72 h after the first dose. Results Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target C min range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, C min ≥ 20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a C min ≥ 20 μg/mL. Conclusion A target C min ≥ 20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.