ANTIMICROBIAL ACTIVITY OF MDL-63,246, A NEW SEMISYNTHETIC GLYCOPEPTIDE ANTIBIOTIC

MDL 63,246 is a semisynthetic derivative of the naturally occurring gl ycopeptide antibiotic MDL 62,476 (A40926). It was more active in vitro against Staphylococcus aureus and coagulase negative staphylococci th an MDL 62,476, teicoplanin, and vancomycin and was more active than mi deplanin (MDL 62,873) against some isolates. MDL 63,246 had excellent activity against streptococci and teicoplanin-susceptible enterococci, and it also had in vitro activity against some VanA enterococcal isol ates. It was more active than teicoplanin and vancomycin against acute staphylococcal, streptococcal, and enterococcal septicemia in immunoc ompetent and neutropenic mice. It was highly efficacious in reducing t he bacterial load in the hearts of rats in staphylococcal endocarditis experiments and the bacterial load of Staphylococcus epidermidis in a thigh infection model in neutropenic mice. The excellent in vivo acti vity of MDL 63,246 appears to correlate both with its in vitro antibac terial activity and with its long half-life in rodents.