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著者: Marilyn N Martinez, Mark G Papich, George L Drusano
雑誌名: Antimicrob Agents Chemother. 2012 Jun;56(6):2795-805. doi: 10.1128/AAC.05360-11. Epub 2012 Feb 27.
Abstract/Text
To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent suboptimal systemic drug concentrations prior to the attainment of a steady state. Suboptimal (inadequate) exposure can produce amplification of resistant bacteria. This minireview provides an overview of published evidence supporting the positions that, in most situations, it is the exposure achieved during the first dose that is relevant for determining the therapeutic outcome of an infection, therapeutic intervention should be initiated as soon as possible to minimize the size of the bacterial burden at the infection site, and the duration of drug administration should be kept as brief as clinically appropriate to reduce the risk of selecting for resistant (or phenotypically nonresponsive) microbial strains. To support these recommendations, we briefly discuss data on inoculum effects, persister cells, and the concept of time within some defined mutation selection window.
PMID 22371890 Antimicrob Agents Chemother. 2012 Jun;56(6):2795-805. doi: 10.1128/AAC.05360-11. Epub 2012 Feb 27.
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