Defining the unbound target exposure of teicoplanin part 1: Insights from the Hollow-Fibre System

Abstract Objectives Teicoplanin is a glycopeptide antibiotic commonly used to treat infections caused by Gram-positive bacteria. Unlike the related vancomycin, therapeutic drug monitoring (TDM) is not consistently applied for teicoplanin. To optimize its clinical use, well-defined pharmacokinetic/pharmacodynamic (PK/PD) targets are needed. Methods An in vitro Hollow-fibre System (HFS) was employed to expose four clinically relevant strains, methicillin-susceptible S. aureus (MSSA) ATCC 29213 (MIC 0.5 mg/L), methicillin resistant S. aureus (MRSA) NCTC 12493 (MIC 0.25 mg/L), S. epidermidis ATCC 12228 (MIC 0.5 mg/L), and E. faecium ATCC 19634 (MIC 0.25 mg/L), to teicoplanin, simulating human pharmacokinetic profiles. Bacterial- and teicoplanin concentrations were measured throughout the period. PK/PD modelling was employed to determine clinical PK/PD targets. Results A PK/PD model assuming the presence of a pre-existing resistant bacterial population was used to capture the PD characteristics of teicoplanin to all four strains. A 1-log₁₀ reduction in bacterial density after 24h was observed under teicoplanin exposure of an fAUC of 15.5mg*h/L for E. faecium, 24.9 mg*h/L for S. epidermidis, 10.5 mg*h/L for MRSA and 75.4 mg*h/L for MSSA. An fAUC of approximately 75.4 mg*h/L was sufficient to achieve at least a 1-log₁₀ kill for all tested strains. Conclusions A teicoplanin fAUC of 75 mg*h/L was shown to achieve an 1-log₁₀ kill after 24h for all strains in the HFS, within the range of the tested MICs. Clinical relevance of this unbound pharmacokinetic target needs to be confirmed in a clinical trial.