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Year : 2017  |  Volume : 35  |  Issue : 3  |  Page : 340-346

Optimisation of antimicrobial dosing based on pharmacokinetic and pharmacodynamic principles

1 Department of Pharmacy, Tan Tock Seng Hospital, Singapore
2 Department of Pharmacy, Singapore General Hospital, Singapore
3 Department of Pharmacy, Singapore General Hospital; Emerging Infectious Diseases, Duke-National University of Singapore; Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore

Correspondence Address:
Andrea Lay-Hoon Kwa
Department of Pharmacy, Singapore General Hospital, Outram Road 169 608
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_17_278

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While suboptimal dosing of antimicrobials has been attributed to poorer clinical outcomes, clinical cure and mortality advantages have been demonstrated when target pharmacokinetic (PK) and pharmacodynamic (PD) indices for various classes of antimicrobials were achieved to maximise antibiotic activity. Dosing optimisation requires a good knowledge of PK/PD principles. This review serves to provide a foundation in PK/PD principles for the commonly prescribed antibiotics (β-lactams, vancomycin, fluoroquinolones and aminoglycosides), as well as dosing considerations in special populations (critically ill and obese patients). PK principles determine whether an appropriate dose of antimicrobial reaches the intended pathogen(s). It involves the fundamental processes of absorption, distribution, metabolism and elimination, and is affected by the antimicrobial's physicochemical properties. Antimicrobial pharmacodynamics define the relationship between the drug concentration and its observed effect on the pathogen. The major indicator of the effect of the antibiotics is the minimum inhibitory concentration. The quantitative relationship between a PK and microbiological parameter is known as a PK/PD index, which describes the relationship between dose administered and the rate and extent of bacterial killing. Improvements in clinical outcomes have been observed when antimicrobial agents are dosed optimally to achieve their respective PK/PD targets. With the rising rates of antimicrobial resistance and a limited drug development pipeline, PK/PD concepts can foster more rational and individualised dosing regimens, improving outcomes while simultaneously limiting the toxicity of antimicrobials.


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2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

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