Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid.
Time above MIC for free drug concentrations is the important PK-PD parameter correlating with the efficacy of beta-lactam antibiotics. The duration of time plasma concentrations needed to exceed the MIC is relatively similar for most organisms except staphylococci. Neutrophils contribute very little to the overall activity of beta-lactams. The appearance of increasing antimicrobial resistance can challenge the efficacy of these drugs when concentrations do not exceed the MIC for 40% to 50% of the dosing interval. Time above MIC with oral amoxicillin and amoxicillin-clavulanate can be enhanced with high-dose formulations. Time above MIC with parenteral preparations can be enhanced by longer intravenous infusions or even continuous infusion. The 24-hour AUC-MIC is probably the important PK-PD parameter correlating with the efficacy of vancomycin and teicoplanin. It clearly is the important parameter for the efficacy of linezolid. Usual doses of these drugs generally provide adequate plasma concentrations to treat effectively infections in which plasma concentrations are predictive of tissue concentrations. Penetration of these drugs into respiratory secretions, such as ELF, is enhanced for linezolid and reduced for vancomycin. This may give linezolid an advantage over vancomycin in certain respiratory infections.
Craig
William A
WA
University of Wisconsin and William S. Middleton Memorial VA Hospital, 2500 Overlook Terrace, Room D-2221, Madison, WI 53705, USA. wac@medicine.wisc.edu
D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy*; D006020:Glycopeptides; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D006020:Glycopeptides; D023303:Oxazolidinones; D000069349:Linezolid