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-100766), and steady-state samples were drawn at the projected peak and trough timepoints. Serum inhibitory titer and serum bactericidal titer values were determined using single strains of Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Serum inhibitory titer values generally correlated with drug concentration in serum and inherent 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 effect. No bactericidal activity was seen for either drug against S. aureus or E. faecalis. The sera from patients dosed with either drug exhibited inhibition of S. pneumoniae at peak and trough. Bactericidal activity 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 regimens. The results demonstrated that the sera from most human subjects dosed with eperezolid or linezolid were inhibitory to S. aureus and E. faecalis and S. pneumoniae and that many of the samples exhibited bactericidal activity for S. pneumoniae.
Schaadt
R D
RD
Infectious Diseases Research, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001, USA.
Batts
D H
DH
Daley-Yates
P T
PT
Pawsey
S D
SD
Stalker
D J
DJ
Zurenko
G E
GE
D000081:Acetamides / Q000008:administration & dosage* / Q000097:blood; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007275:Injections, Intravenous; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000008:administration & dosage* / Q000097:blood; D023303:Oxazolidinones; D011008:Pneumococcal Infections / Q000097:blood / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D010080:Oxazoles; D023303:Oxazolidinones; C098011:eperezolid; D000069349:Linezolid