Pharmacokinetic and experimental data on beta-lactam antibiotics in the treatment of patients.
The in vitro and animal model studies on optimal dosage of the newer beta-lactams are summarized and put into historical perspective. They provide a rationale for dosage schedules that continuously maintain inhibitory serum and tissue concentrations throughout the dosage interval. In vitro studies on the post-antibiotic effect (PAE) with beta-lactams revealed only short time periods of post-antibiotic growth suppression with gram-positive cocci and no post-antibiotic effect with gram-negative bacilli. A similar lack of persistent growth suppression was observed with beta-lactams in a neutropenic mouse thigh infection model for both gram-positive and gram-negative bacteria. In the same animal model, dosing regimens of beta-lactams which continuously provided serum concentrations above the MIC were more efficacious than those that did not. The newer third-generation cephalosporins have prolonged half-lives and can maintain serum levels above the MIC for most pathogens, even when dosed at widely spaced intervals.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams