Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections.
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.
Moise-Broder
Pamela A
PA
CPL Associates, LLC, Amherst, New York, USA.
Forrest
Alan
A
Birmingham
Mary C
MC
Schentag
Jerome J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014640:Vancomycin