SERUM INHIBITORY TITERS AND SERUM BACTERICIDAL TITERS FOR HUMAN-SUBJECTS RECEIVING MULTIPLE DOSES OF THE ANTIBACTERIAL OXAZOLIDINONES EPEREZOLID AND LINEZOLID

In Phase I trials subjects received multiple doses of eperezolid (PNU- 100592; formerly U-100592) and linezolid (PNU-100766; formerly U-10076 6), and steady-state samples were drawn at the projected peak and trou gh timepoints. Serum inhibitory titer and serum bactericidal titer val ues were determined using single strains of Staphylococcus aureus, Ent erococcus faecalis, and Streptococcus pneumoniae. Serum inhibitory tit er values generally correlated with drug concentration in serum and in herent organism susceptibility. Against S. aureus and E. faecalis sera from patients dosed with either drug were generally inhibitory at the peak timepoint, but at trough only linezolid exhibited a persistent e ffect. No bactericidal activity was seen for either drug against S. au reus or E. faecalis. The sera from patients dosed with either drug exh ibited inhibition of S. pneumoniae at peak and trough. Bactericidal ac tivity was seen against S. pneumoniae for both drugs at peak time and at trough for many of the sera for patients on the higher dose regimen s. The results demonstrated that the sera from most human subjects dos ed with eperezolid or linezolid were inhibitory to S. aureus and E. fa ecalis and S. pneumoniae and that many of the samples exhibited bacter icidal activity for S. pneumoniae. (C) 1997 Elsevier Science Inc.