Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (C_min) was ≥15–30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m²) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7–10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial C_min compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial C_min ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34–13.15). In patients with 15–30 μg/ml of maximal C_min during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of C_min of 15–30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.