Quaternary heterocyclylamino beta-lactams. IV. Comparison of the in vivo antibacterial activities of L-640,876, mecillinam, cefoxitin and cefotaxime.
The novel beta-lactam, L-640,876, exhibited excellent therapeutic activity when administered parenterally but not orally to mice infected with a variety of pathogenic bacteria. In this respect, the compound was as potent as cefotaxime against representative Gram-positive and Gram-negative organisms, in most cases, equal to or more potent than cefoxitin, and more effective than mecillinam. When administered subcutaneously to normal mice at dose levels ranging from 10 to 50 mg/kg, L-640,876 provided an adequate dose response, recovery of ca. 45% of biological activity in the urine, and excellent distribution at the highest dose level into liver, lung, kidney, heart muscle, but not brain.
D000560:Amdinocillin / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology* / Q000627:therapeutic use; D002440:Cefoxitin / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D002440:Cefoxitin; C042505:L 640876; D010397:Penicillanic Acid; D002439:Cefotaxime; D000560:Amdinocillin