title: 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 microg/ml against all isolates; MIC90s being 4.0, 1.0, 2.0, 2.0 and 2.0 microg/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 microg/ml against all isolates, with MIC90s of 2.0, 4.0, 4.0, 4.0 and 2.0 microg/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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat, Kuwait. dphillips@hsc.kuniv.edu.kw
authors.forename: O A
authors.initials: OA
authors.lastname: Phillips
authors.forename: V O
authors.initials: VO
authors.lastname: Rotimi
authors.forename: W Y
authors.initials: WY
authors.lastname: Jamal
authors.forename: M
authors.initials: M
authors.lastname: Shahin
authors.forename: T L
authors.initials: TL
authors.lastname: Verghese
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D016360:Clostridioides difficile / Q000187:drug effects*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; C477255:PH 027; D014230:Triazoles; D000069349:Linezolid