Reduced Immunotoxicity and Preservation of Antibacterial Activity in a Releasable Side-Chain Carbapenem Antibiotic

The increasing prevalence of resistance in Staphylococci and Enterococci to currently available antimicrobials has resulted in the significant diminution of therapeutic options available. Patients infected with multi-drug resistant organisms are [...]
A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycinresistant Staphylococci and vancomycin-resistant Enterococci.