title: AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity.
abstract: AFN-1252, a potent inhibitor of enoyl-acyl carrier protein reductase (FabI), inhibited all clinical isolates of Staphylococcus aureus (n = 502) and Staphylococcus epidermidis (n = 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of <or=0.12 microg/ml. In contrast, AFN-1252 was inactive (MIC(90), >4 microg/ml) against clinical isolates of Streptococcus pneumoniae, beta-hemolytic streptococci, Enterococcus spp., Enterobacteriaceae, nonfermentative gram-negative bacilli, and Moraxella catarrhalis. These data support the continued development of AFN-1252 for the treatment of patients with resistant staphylococcal infections.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. jkarlowsky@hsc.mb.ca
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: Nachum
authors.initials: N
authors.lastname: Kaplan
authors.forename: Barry
authors.initials: B
authors.lastname: Hafkin
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology; D016983:Enterococcus / Q000187:drug effects / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000201:enzymology; D011753:Pyrones / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013210:Staphylococcus / Q000187:drug effects* / Q000201:enzymology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000201:enzymology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000201:enzymology
chemical_list: C521531:API 1252; D000900:Anti-Bacterial Agents; D001572:Benzofurans; D011753:Pyrones; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)