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Clinical Pharmacokinetics

Erschienen in:

01.11.2004 | Original Research Article

Pharmacodynamics of Vancomycin and Other Antimicrobials in Patients with Staphylococcus aureus Lower Respiratory Tract Infections

verfasst von: Pamela A. Moise-Broder, Alan Forrest, Mary C. Birmingham, Dr Jerome J. Schentag

Erschienen in: Clinical Pharmacokinetics | Ausgabe 13/2004

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Abstract

Background

Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation.

Objective

To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases.

Methods

We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC₂₄) divided by the MIC (AUC₂₄/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC₂₄/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC₂₄/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms.

Results

The median age of the 108 patients studied was 74 (range 32–93) years. Measured vancomycin AUC₂₄/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r² = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (≥400) AUC₂₄/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC₂₄/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score.

Conclusions

Vancomycin AUC₂₄/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.

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Titel: Pharmacodynamics of Vancomycin and Other Antimicrobials in Patients with Staphylococcus aureus Lower Respiratory Tract Infections
verfasst von: Pamela A. Moise-Broder
Alan Forrest
Mary C. Birmingham
Dr Jerome J. Schentag
Publikationsdatum: 01.11.2004
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 13/2004
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200443130-00005

Springer Medizin

Abstract

Background

Objective

Methods

Results

Conclusions

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