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)/MICMethods
≥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<0.01); fAUC/MIC and AUC/MIC did not (Spearman’s Rank Correlation Coef-ficient R=0.36; 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.