In vitro antibacterial activity of PNU-288034, a novel oxazolidinone antibiotic

Abstract

Background: Linezolid is the first oxazolidinone-class compound to be marketed for the treatment of bacterial infections in humans. Research has now focused on the enhancement of the spectrum and/or antibacterial potency of the oxazolidinone template. PNU-288034 is a novel analog from that effort. Methods: The antibacterial activity of PNU-288034 was assessed by a variety of methods. Minimal Inhibitory Concentration (MIC) values for PNU-288034 and comparator compounds against a battery of 284 aerobic and 44 anaerobic bacteria were determined using standard methods. The activity of the compound was assessed against both laboratory-derived and clinical isolates of linezolid-resistant bacteria. The effects of modified susceptibility test conditions on antibacterial activity were determined. Results: PNU-288034 demonstrated potent activity against all of the Gram-positive organisms tested, including antibiotic-resistant strains. Nearly all Gram-positive strains tested were inhibited at concentrations ltoreq2.0 mug/ml. PNU-288034 exhibited moderate activity against the fastidious Gram-negative organisms included in the study. In general the MIC values for PNU-288034 were comparable to those of linezolid against the anaerobic bacteria tested. PNU-288034 was cross-resistant with linezolid for laboratory-derived resistant mutants of Staphylococcus aureus and Enterococcus faecalis and for clinical isolates of linezolid-resistant enterococci. The compound demonstrated robust activity which was generally unaffected by modified susceptibility test conditions such as incubation conditions (temperature and atmosphere), pH of test medium, and the presence of serum. Conclusions: PNU-288034 is a novel oxazolidinone analog with in vitro antibacterial activity comparable to or slightly better than that of linezolid.