Antimicrobial activity of MDL 62,873, a semisynthetic derivative of teicoplanin, in vitro and in experimental infections.
MDL 62,873 is an amide derivative of teicoplanin A2-2. Like those of natural glycopeptides, its antibacterial activity is mediated by inhibition of cell wall peptidoglycan synthesis. Against streptococci and enterococci, the in vitro activity of MDL 62,873 was similar to that of teicoplanin and greater than that of vancomycin. Against staphylococci, it has activity similar to that of vancomycin, and it was significantly more active than teicoplanin against coagulase-negative isolates. Like teicoplanin and vancomycin, MDL 62,873 had slow but significant bactericidal activity (99 to 99.9% killing in 24 h) against staphylococci at concentrations near the MIC. In murine septicemia studies with Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, the 50% effective doses were lower than those of vancomycin. In staphylococcal endocarditis in rats, MDL 62,873 at 20 mg/kg of body weight and vancomycin at 40 mg/kg, both doses given intravenously twice daily, had similar efficacies in reducing the heart bacterial load. These results probably reflect the longer half-life of MDL 62,873, which has a pharmacokinetic profile in rats similar to that of teicoplanin.
Berti
M
M
Lepetit Research Center, Marion Merrell Dow Research Institute, Gerenzano (Varese), Italy.
Candiani
G
G
Borgonovi
M
M
Landini
P
P
Ripamonti
F
F
Scotti
R
R
Cavenaghi
L
L
Denaro
M
M
Goldstein
B P
BP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000382:microbiology; D006020:Glycopeptides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006207:Half-Life; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D012310:Ristocetin / Q000031:analogs & derivatives; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects; D017334:Teicoplanin
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C068029:MDL 62873; D012310:Ristocetin; D017334:Teicoplanin