Retrospective review of serum teicoplanin concentrations in clinical trials and their relationship to clinical outcome

Twenty-five published clinical studies were reviewed in which teicoplanin serum concentrations were determined. A variety of assay methods were used, including bioassay, solid phase enzyme receptor assay, HPLC and immunoassay, and in some studies, more than 1 methodology was used. Fourteen studies gave sufficient data on the method of assay, timing of assays relative to dosage or during therapy, and route of administration of teicoplanin to be included in a detailed pharmacokinetic analysis. Since a wide range of dosing regimens were employed, the studies were grouped in order to facilitate analysis according to the teicoplanin maintenance dose, either 200mg, 400mg or 6mg/kg/day. Six studies used a dose of 200mg/day and although the mean trough concentrations varied by as much as 3-fold, they did not exceed 10mg/L in the first 7 days of therapy. Six studies used a 400mg/day maintenance dose and the mean trough concentrations varied from 4 to 11mg/L on days 1–2, to 9 to 17mg/L on days 6–7 of therapy. In 5 of these studies, the mean trough concentration was less than 10mg/L for the first 48 hours of treatment. In 2 studies where a dose of 6mg/kg/day was used, the mean concentrations did not exceed 10mg/L until day 7, while in the other study they were greater than 10mg/L beginning on day 1. A retrospective analysis of 58 clinical cases reported in the literature, 42 of whom had staphylococcal infections, indicated that serum concentrations and teicoplanin concentration/MIC ratios were related to clinical cure particularly for patients with staphylococcal infections. Trough concentrations of greater than 10mg/L were related to favorable outcomes when all 58 patients were analyzed and trough concentrations of greater than 20mg/L were related to cure for those who had staphylococcal infections. While retrospective in nature, this review indicates that there is considerable variation in teicoplanin pharmacokinetics in the different patient groups, only some of which is related to differences in dosing, timing of blood collection for assay or assay methodology. In addition, these data suggest that pharmacokinetic parameters such as trough and postdose teicoplanin concentrations, and phamracodynamic factors such as serum concentration MIC ratios may be related to clinical outcome with teicoplanin therapy.