From bench to bedside: how dynamic hollow-fibre in vitro infection experiments and mathematical modelling can inform pharmacokinetic/pharmacodynamic targets for teicoplanin

Infections caused by Gram-positive pathogens are a major cause of morbidity and mortality, with increasing rates of antimicrobial resistance and limited treatment options necessitating their prioritization for research. The glycopeptide antibiotic teicoplanin is used in the European Union, Asia (including Japan, Korea, and China) and Australia against severe infections caused by vancomycin-susceptible and vanB vancomycin-resistant Enterococcus faecium, methicillin-susceptible and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis [1]. The ratio of the unbound area under the plasma concentration-time curve to the MIC (fAUC/MIC) is considered as the pharmacokinetic/pharmacodynamic (PK/PD) index that best predicts the antibacterial activity of glycopeptides, including teicoplanin [2]. However, there is a lack of evidence on which fAUC/MIC target value is required for teicoplanin to achieve various magnitudes of bacterial kill, such as stasis, or 1- or 2-log10 reduction in counts of viable bacterial cells, across different pathogens. This gap in knowledge limits the ability to optimize dosing of teicoplanin to maximize the probability of clinical success for infected patients. Thus, the study by Mouton et al. [3] published in this issue of Clinical Microbiology and Infection, which sought to define the fAUC/MIC target value for teicoplanin, is highly welcome in generating clinically relevant knowledge to address this gap and provides an important addition to the literature.