Influence of Human Serum on Pharmacodynamic Properties of an Investigational Glycopeptide, LY333328, and Comparator Agents against Staphylococcus aureus

The MICs and MBCs of 15 antibiotics for two strains of Staphylococcus aureus were determined in Mueller-Hinton broth (MHB) and 90% serum–10% MHB. Subsequent experiments established that highly protein-bound antibiotics (≥80%), such as LY333328, demonstrated higher MICs and MBCs, less killing over an 8-h interval, and shorter postantibiotic effects in 90% serum–10% MHB than in MHB alone. Albumin was demonstrated to be almost solely responsible for changes in the aforementioned pharmacodynamic parameters of LY333328.