Methods: Multiple data sources were considered, including longitudinal USA reference MIC surveillance distributions using data collected over 18 years (SENTRY Antimicrobial Surveillance Program, TEST, etc.), QC parameters (MIC, disk diffusion), population pharmacokinetics (PK), and clinical and/or animal pharmacokinetic-pharmacodynamic (PK-PD) models. Using population PK models, AUC:MIC ratio targets for AMG efficacy and Monte Carlo simulation, probabilities of PK-PD target attainment by MIC value for the safer once-daily AMG dosing regimens (5 and 7.5 mg/kg for GEN and TOB; 20 and 30 mg/kg for AMI) were evaluated. Epidemiological cut-off, PK-PD and clinical BKPTs were determined and considered when recommending BKPTs for AMG-pathogen pairs.
Results: A subset of recommended AMG BKPTs for three pathogens is shown in Table 1. These USCAST BKPTs, which were based on the application of population PK and PK-PD models, simulation techniques and contemporary MIC distribution statistics, were generally lower than those of EUCAST/EMA, USA-FDA and CLSI. Adequate probabilities of PK-PD target attainment were not achieved for some AMG-pathogen pairs, even when the highest AMG dosing regimens were evaluated (examples: GEN vs. P. aeruginosa; AMI vs. S. aureus).
D. R. Andes, None
J. S. Bradley, None
W. A. Craig, None
G. L. Drusano, None
R. N. Jones, None
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