Does the Dose Matter?

Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak to minimum inhibitory concentration (peak/MIC ratio), ratio of 24-hour area under the curve to MIC (24-h AUC/MIC ratio), and the time above MIC, are good indicators of the drug dose—organism interaction. Time above the MIC...

Full description

Saved in:
Bibliographic Details
Published in:Clinical infectious diseases 2001-09, Vol.33 (Supplement-3), p.S233-S237
Main Author: Craig, William A.
Format: Article
Language:English
Subjects:
Aminoglycosides
Animal models
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobials
Biological and medical sciences
Dosage
Dose-Response Relationship, Drug
Drug design
Drug Resistance, Bacterial
Fluoroquinolones
Humans
Infections
Macrolides
Medical sciences
Microbial Sensitivity Tests
Mutagenesis - drug effects
Pharmacology. Drug treatments
Streptococcus pneumoniae
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak to minimum inhibitory concentration (peak/MIC ratio), ratio of 24-hour area under the curve to MIC (24-h AUC/MIC ratio), and the time above MIC, are good indicators of the drug dose—organism interaction. Time above the MIC is the important determinant of the activity of β-lactams, macrolides, clindamycin, and linezolid. Free drug serum levels of these drugs should be above the MIC for at least 40%–50% of the dosing interval to produce adequate clinical and microbiological efficacy. Peak/MIC and 24-h AUC/MIC ratios are major determinants of the activity of aminoglycosides and fluoroquinolones. In general, peak/MIC ratios should exceed 8 and 24-h AUC/MIC values should be >100 to successfully treat gram-negative bacillary infections and to prevent the emergence of resistant organisms during therapy. The successful treatment of pneumococcal infections with fluoroquinolones and azithromycin appear to require 24-h AUC/MIC ratios of only 25–35. Mutation prevention concentrations are being reported for various fluoroquinolones with different pathogens, but their clinical significance has not yet been established. More information is needed on the role of PK/PD parameters and their magnitude for preventing mutations and the emergence of resistant organisms for most classes of antibiotics.
ISSN:1058-4838
1537-6591
DOI:10.1086/321854