Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections.

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 (> or = 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.

• Authors: Pamela A Moise-Broder, Alan Forrest, Mary C Birmingham, Jerome J Schentag
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) Vol. 43 Issue 13 Pg. 925-42 ( 2004) ISSN: 0312-5963 [Print] Switzerland
• PMID: 15509186 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Anti-Bacterial Agents
• Vancomycin

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Area Under Curve
• Female
• Hospitals, Teaching
• Humans
• Male
• Methicillin Resistance
• Microbial Sensitivity Tests
• Middle Aged
• Respiratory Tract Infections (drug therapy)
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus (drug effects)
• Time Factors
• Treatment Outcome
• Vancomycin (pharmacology, therapeutic use)