Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections

Abstract

Background: Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration-time curve (AUC)/minimum inhibitory concentration (MIC) was identified as a pharmacokinetic-pharmacodynamic (PK-PD) parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK-PD are needed, a PK-PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio.

Methods: This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM) of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24). The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment.

Results: The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 µg·h/mL (n=34) and 642.2±193.9 µg·h/mL, respectively (n=12; P<0.05). On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 µg·h/mL, 700 µg·h/mL, and 900 µg·h/mL gave probabilities of treatment success of 0.50, 0.72, and 0.87, respectively. Furthermore, using the Kaplan-Meier curve analysis, an AUC24/MIC ratio of ≥900 led to a significantly stronger bacteriological response than an AUC24/MIC ratio of <900.

Conclusion: These results suggest that an AUC24/MIC ratio of ≥900 µg·h/mL is required to ensure a sufficient bacteriological response.

Keywords: AUC/MIC; MRSA; PK/PD; teicoplanin.

Figures

Figure 1

Teicoplanin AUC24/MIC ratio and logistic regression model for bacteriological responses (failure, 0; success, 1). Abbreviations: AUC24, area under the concentration–time curve for 24 hours; MIC, minimum inhibitory concentration.

Figure 2

Kaplan–Meier plot showing the time from the initiation of teicoplanin therapy to efficacy rates between the AUC24/MIC ratios of ≥900 (n=15) and <900 (n=31). Abbreviations: AUC24, area under the concentration–time curve for 24 hours; MIC, minimum inhibitory concentration.