Defining the unbound target exposure of teicoplanin, Part 1: Insights from the hollow-fibre system.

OBJECTIVES

Teicoplanin is a glycopeptide antibiotic commonly used to treat infections caused by gram-positive bacteria. Unlike the related vancomycin, therapeutic drug monitoring 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 was used to expose four clinically relevant strains, methicillin-susceptible Staphylococcus aureus American Type Culture Collection (ATCC) 29213 (minimum inhibitory concentration [MIC] 0.5 mg/L), methicillin-resistant S. aureus National Collection of Type Cultures (NCTC) 12493 (MIC 0.25 mg/L), Staphylococcus epidermidis ATCC 12228 (MIC 0.5 mg/L), and Enterococcus 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 used 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 24 hours was observed under teicoplanin exposure of an area under the unbound concentration-time curve (fAUC) of 15.5 mg h/L for E. faecium, 24.9 mg h/L for S. epidermidis, 10.5 mg h/L for methicillin-resistant S. aureus, and 75.4 mg h/L for methicillin-susceptible S. aureus. 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 a 1-log10 kill after 24 hours for all strains in the hollow-fibre system, within the range of the tested MICs. Clinical relevance of this unbound pharmacokinetic target needs to be confirmed in a clinical trial.