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Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on β‐Lactam Antibiotics
Author(s) -
Lodise Thomas P.,
Lomaestro Ben M.,
Drusano George L.
Publication year - 2006
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.26.9.1320
Subject(s) - meropenem , cefepime , dosing , pharmacodynamics , pharmacokinetics , piperacillin , minimum inhibitory concentration , medicine , antibiotics , tazobactam , antimicrobial , pharmacology , piperacillin/tazobactam , population , intensive care medicine , microbiology and biotechnology , biology , antibiotic resistance , bacteria , pseudomonas aeruginosa , imipenem , genetics , environmental health
In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of β‐lactams and microbiologic response. For β‐lactams, in vitro and animal studies suggest that the amount of time in which free or non–protein‐bound antimicrobial concentration exceeds the minimum inhibitory concentration (MIC) of the organism ( f T>MIC) is the best predictor of bacterial killing and microbiologic response. Using population pharmacokinetic modeling and Monte Carlo simulation, it is possible to integrate pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate empiric β‐lactam dosing strategies that maximize the likelihood of achieving f T>MIC associated with near‐maximal bactericidal effect against the range of pathogens encountered in clinical practice. At Albany Medical Center Hospital, these mathematical modeling techniques were used to devise alternative dosing schemes for piperacillin‐tazobactam, meropenem, and cefepime. These alternative schemes optimized f T>MIC at a lower total daily dose than would be employed with traditional dosing methods. Moreover, they achieved the targeted f T>MIC with less administration time/day than would be needed for continuous infusion.