Comparative in vitro activity of PH-027 versus linezolid and other anti-anaerobic antimicrobials against clinical isolates of Clostridium difficile and other anaerobic bacteria. 2003

O A Phillips, and V O Rotimi, and W Y Jamal, and M Shahin, and T L Verghese
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat, Kuwait. dphillips@hsc.kuniv.edu.kw

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.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D000069349 Linezolid An oxazolidinone and acetamide derived ANTI-BACTERIAL AGENT and PROTEIN SYNTHESIS INHIBITOR that is used in the treatment of GRAM-POSITIVE BACTERIAL INFECTIONS of the skin and respiratory tract. Linezolide,N-((3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide,PNU-100766,U 100766,U-100766,Zyvox,100766, U,PNU 100766,PNU100766,U100766
D000081 Acetamides Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001421 Bacteria, Anaerobic Bacteria that can survive and grow in the complete, or nearly complete absence of oxygen. Anaerobic Bacteria
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D016360 Clostridioides difficile A common inhabitant of the colon flora in human infants and sometimes in adults. The type species Clostridioides difficile is formerly known as Clostridium difficile. It is a causative agent for CLOSTRIDIOIDES INFECTIONS and is associated with PSEUDOMEMBRANOUS ENTEROCOLITIS in patients receiving antibiotic therapy. Clostridium difficile
D023303 Oxazolidinones Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. 1,3-Oxazolidin-2-one,Oxazolidin-2-one,Oxazolidinone,1,3-Oxazolidine-2-one,2-Oxazolidone,2-oxazolidinone,1,3 Oxazolidin 2 one,1,3 Oxazolidine 2 one,2 Oxazolidone,2 oxazolidinone,Oxazolidin 2 one

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