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Use of a clinically derived exposure-response relationship to evaluate potential tigecycline-Enterobacteriaceae susceptibility breakpoints.

Abstract：

:Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value. Using a previously derived tigecycline population pharmacokinetic model and Monte Carlo simulation, a probability density function of steady-state area under the concentration-time curve for 24 h (AUC(SS(0-24))) values for 9999 patients was generated. AUC(SS(0-24)) values were divided by clinically relevant fixed MIC values to derive AUC(SS(0-24))/MIC ratios, which were used to calculate the clinical response expectation by MIC value based upon a logistic regression model for efficacy (1st approach). For the 2nd approach, the probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment was calculated as the proportion of patients with AUC(SS(0-24))/MIC ratios greater than the threshold value of 6.96, the PK-PD target associated with optimal clinical response. Probabilities of clinical response and PK-PD target attainment were poorly correlated at MIC values >0.25 mg/L. For instance, the median probability of clinical success was 0.76, whereas the probability of PK-PD target attainment was 0.27 at an MIC value of 1 mg/L, suggesting that the probability of PK-PD target attainment metrics underestimates the clinical performance of tigecycline at higher MIC values.

journal_name

Diagn Microbiol Infect Dis

journal_title

Diagnostic microbiology and infectious disease

authors

Ambrose PG,Meagher AK,Passarell JA,Van Wart SA,Cirincione BB,Rubino CM,Korth-Bradley JM,Babinchak T,Ellis-Grosse E

doi

10.1016/j.diagmicrobio.2008.09.014

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

38-42

issue

1

eissn

0732-8893

issn

1879-0070

pii

S0732-8893(08)00414-8

journal_volume

63

pub_type

杂志文章

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