Comparative In Vitro Activity of PH-027 Versus Linezolid and Other Anti-Anaerobic Antimicrobials Against Clinical Isolates of Clostridium difficile and Other Anaerobic Bacteria

Abstract

PH-027 is a new 5-triazole oxazolidinone synthesized in our laboratories, which shows strong activity against Gram-positive aerobic bacteria including clinical isolates. The objective of this study was to investigate the In Vitro activity of this compound in comparison with linezolid and other antibiotics against Gram-positive and Gram-negative anaerobes. The In Vitro activity of PH-027 in comparison with those of linezolid and other antimicrobial agents was evaluated against 201 clinical isolates of Gram-positive and Gram-negative anaerobic bacteria by agar dilution and Etest methods.

PH-027 showed excellent activity, with minimum inhibitory concentrations (MIC) in the range of 0.12-4.0 μg/ml against all isolates; MIC₉₀s being 4.0, 1.0, 2.0, 2.0 and 2.0 μg/ml against Clostridium difficile, Peptostreptococcus spp., Bacteroides fragilis, Prevotella bivia and Fusobacterium spp. respectively. In comparison, linezolid had MIC in the range of 0.5-4.0 μg/ml against all isolates, with MIC₉₀s of 2.0, 4.0, 4.0, 4.0 and 2.0 μg/ml against the same set of bacteria respectively. PH-027 demonstrated excellent In Vitro activity that is superior to linezolid against Peptostreptococcus spp., B. fragilis and P. bivia. However, against C. difficile and Fusobacterium spp, PH-027 and linezolid showed comparable In Vitro activity. Against all anaerobes, metronidazole, PH-027 and, to a lesser extent, linezolid had the most potent activity. From the results of In Vitro susceptibility testing, both linezolid and PH-027 show promise in the treatment of anaerobic infections.