Trius Therapeutics, Inc. today reported new findings on torezolid phosphate (TR-701), a second generation oxazolidinone antibiotic now in Phase 3 clinical development. The data elucidate the mechanism by which torezolid retains full activity against clinical isolates of Staphylococcus aureus (S. aureus) carrying the cfr gene which confers resistance to first generation oxazolidinones such as linezolid, marketed by Pfizer as Zyvox®. Hospital outbreaks of linezolid resistant cfr strains of methicillin-resistant Staphylococcus aureus (MRSA) have been reported worldwide and increasing use of linezolid may promote further dissemination of this plasmid borne resistance gene. Two separate articles featuring discussion of these data have been published online ahead of print on Sept. 13 in Antimicrobial Agents and Chemotherapy (AAC), a journal of the American Society for Microbiology.
S. aureus that express the cfr gene possess ribosomes that are structurally altered in a way that inhibits the binding of first generation oxazolidinone antibiotics such as linezolid, as well as the binding of antibiotics of other classes, such as the pleuromutilins, phenicols, lincosamides, and streptogramins. Torezolid's potent activity is preserved against cfr strains of S. aureus due to its unique structural features.
"Recent outbreaks of cfr strains of MRSA have fueled concerns that this pathogen will inevitably proliferate given the broad usage of linezolid and generic antibiotics that select for the plasmid borne cfr resistance gene," says Jeffrey Stein, PhD, president and chief executive officer of Trius and corresponding author on the papers. "The potent activity of torezolid against cfr-positive bacteria differentiates it as a true second generation oxazolidinone which may be a solution to emerging linezolid resistance."