Journal Article

Does the Dose Matter?

William A. Craig

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 33, issue Supplement_3, pages S233-S237
Published in print September 2001 | ISSN: 1058-4838
Published online September 2001 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/321854
Does the Dose Matter?

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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.

Journal Article.  3467 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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