Pharmacokinetic and microbiologic evaluation of antibiotic dosage regimens.
A retrospective pharmacokinetic analysis was performed for 165 antibiotic dosage regimens used in treating 15 microorganisms for which the antibiotics are considered to be agents of first choice or primary alternatives. The pharmacokinetic indices assessed were the three components of the steady-state temporal blood concentration profile: (1) the magnitude of the peak blood level at steady state compared with the minimum inhibitory concentration (Cmaxss/MIC); (2) the duration of the blood level above the MIC during each 72-hour period (number of hours per 72-hour period above MIC); and (3) the product of 1 and 2 (the intensity index). Considering the pharmacokinetic indices and antibiotics studied, ampicillin, cefadroxil (p.o.), cefazolin (i.v.), clindamycin, gentamicin, and tetracycline demonstrated the best pharmacokinetic performances for the penicillin, cephalosporin, macrolide-like, aminoglycoside, and tetracycline groups, respectively. The data suggest that some antibiotics may be effective at lower doses than commonly used, while others may need to be used more aggressively. Antibiotics with 80% or greater protein binding show no substantially reduced performance in the pharmacokinetic indices evaluated as compared with antibiotics bound less than 80%. Substantial differences are demonstrated in pharmacokinetic indices for dosage regimens used in treating specific microorganisms for which the antibiotics are considered the agents of choice or primary alternatives.
D000617:Aminoglycosides / Q000008:administration & dosage / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects; D002511:Cephalosporins / Q000008:administration & dosage / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D007700:Kinetics; D010406:Penicillins / Q000008:administration & dosage / Q000378:metabolism; D011485:Protein Binding; D013754:Tetracyclines / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; D013754:Tetracyclines