O-10 An observational study on plasma protein binding and target attainment of teicoplanin in critically ill children

Abstract

Background The objectives of this study were (i) to document teicoplanin plasma protein binding and, (ii) to evaluate target attainment rates using commonly used PK/PD targets in critically ill children. Methods Patients, admitted to the PICU in whom treat-ment with intravenous teicoplanin (10 mg/kg every 12 hour for 3 loading doses, followed by 6–10 mg/kg once daily) was indicated, were enrolled. Blood samples were collect-ed during first and/or assumed steady-state dose inter-vals. Noncompartmental analysis was used to estimate the (free) AUC24h for first and SS doses. Evaluated PK/PD targets included AUC/MIC ≥750 hour, free AUC (fAUC)/MIC ≥75 hour and total trough plasma concentration (Cmin) ≥10 mg/L. Correlation was assessed by means of a scatter plot and Spearman’s Rank Correlation Coefficient. Results 130 plasma samples were collected from 27 pa-tients (median age: 2.2 years; IQR: 0.8–4.8 years). The free teicoplanin fraction (n=26; median: 8.6%; IQR: 7.0%–11.7%) only varied slightly between patients. The targets of AUC/MIC (median: 823 hour; IQR: 702–949 hour) and fAUC/MIC (n=26; median: 72 hour; IQR: 55–86 hour) were achieved in 63% and 42% of patients respectively. The target Cmin (median: 16.0 mg/L; IQR: 10.3–17.9 mg/L) were reached in 78% of patients. Cmin correlated well with AUC/MIC (Spearman’s Rank Correlation Coefficient R=0.84; p 0.05). Conclusion Currently used teicoplanin dosing regimens frequently resulted in an AUC/MIC ratio and Cmin be-low widely accepted PK/PD targets. The fAUC/MIC ratio resulted in the lowest target attainment, despite plasma protein binding was similar to adults. Overall, target at-tainment rates varied widely depending upon the type of PK/PD target used. Future study is needed to define appropriate PK/PD indices in children.