Journal of Antimicrobial Chemotherapy · 2017 · 327 citations · 12 references
MedicinePharmacokineticsPharmacologyAntimicrobial PharmacologyClinical PharmacologyTherapeutic Drug MonitoringAntimicrobial DosingAntimicrobial PharmacodynamicsAntimicrobial Susceptibility TestingDe-escalation Of Antimicrobial TherapyDose OptimizationPharmacokinetics Of AntimicrobialsAntibiotic Dose AdjustmentAntibiotic Dose IndividualizationAntibiotic Dose OptimizationAntimicrobial Dose AdjustmentAntimicrobial Dosing OptimizationAntimicrobial Drug MonitoringMinimum Inhibitory Concentration-guided DosingPharmacokinetic-pharmacodynamic Optimization
Antibiotic dose optimization has been proposed based on MIC values, yet routine laboratory MIC determinations lack sufficient accuracy and exhibit inherent variation that must be considered. This study aims to outline the problems with MIC‑based dosing and propose practical approaches for clinical use. The authors describe methods that combine therapeutic drug monitoring with a single MIC and PK/PD modeling, emphasizing the need to account for MIC variability to avoid underdosing. They conclude that relying on a single MIC determination for dose adjustment is inappropriate.
Over recent decades, several publications have described optimization procedures for antibiotic therapy in the individual patient based on antimicrobial MIC values. Most methods include therapeutic drug monitoring and use a single MIC determination plus the relevant pharmacokinetics/pharmacodynamics to adjust the dose to optimize antimicrobial drug exposure and antibacterial effects. However, the use of an MIC obtained by a single MIC determination is inappropriate. First, routine clinical laboratories cannot determine MICs with sufficient accuracy to guide dosage owing to the inherent assay variation in the MIC test. Second, the variation in any MIC determination, whatever method is used, must be accounted for. If dose adjustments are made based on therapeutic drug monitoring and include MIC determinations, MIC variation must be considered to prevent potential underdosing of patients. We present the problems and some approaches that could be used in clinical practice.
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Michael J. Rybak, Ben M. Lomaestro, John C. Rotscahfer et al. · Clinical Infectious Diseases · 2009 · 809 citations · Full text