Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci

Autor: Paul G. Ambrose, Brenda Cirincione, Sujata M. Bhavnani, Julie A. Passarell, Scott A. Van Wart, Alison K. Meagher, Evelyn J. Ellis-Grosse
Rok vydání: 2008
Předmět:
Zdroj: Diagnostic microbiology and infectious disease. 63(2)
ISSN: 1879-0070
Popis: Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population pharmacokinetic model and Monte Carlo simulation (9999 patients) were used to create a likelihood distribution of tigecycline exposure, as measured by the area under the concentration-time curve at 24 h (AUC(24)). Each resultant AUC(24) value was paired with a clinically relevant fixed MIC value ranging from 0.12 to 2 mg/L. For each AUC(24)-MIC pair, the probability of microbiologic response was calculated using an exposure-response relationship, which was derived from patients with complicated skin and skin structure infections that involved Staphylococcus aureus or streptococci or both. The median probability of microbiologic success was 94% or greater for MIC values up to and including 0.25 mg/L. The median probability of microbiologic success was 66% or less for MIC values of 0.5 mg/L or greater. These data support a susceptibility breakpoint of 0.25 mg/L for S. aureus and streptococci.
Databáze: OpenAIRE