Reduced immunotoxicity and preservation of antibacterial activity in a releasable side-chain carbapenem antibiotic

A carbapenem antibiotic, L-786,392, was designed so that the side chain tha t provides high-affinity binding to the penicillin-binding proteins respons ible for bacterial resistance was also the structural basis for amelioratin g immunopathology. Expulsion of the side chain upon opening of the beta-lac tam ring retained antibacterial activity while safely expelling the immunod ominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and va ncomycin-resistant Staphylococci and vancomycin-resistant Enterococci.