Optimizing use of aminoglycosides in the critically ill.
In the era of increasing bacterial resistance and a lack of development of new antimicrobials for the treatment of gram-negative infections, aminoglycosides (AGs) are more commonly used in combination with other antimicrobials for the treatment of life-threatening infections in the intensive care unit (ICU). AGs display concentration-dependent killing activity; thus the rate and extent of bacterial killing increase with increasing peak (Cmax) drug concentrations. Optimizing AG dosing requires attainment of a pharmacodynamic target ratio (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is associated with a more rapid rate of resolution of infection. Extended-interval AG dosing has been shown to attain this target in the general patient population while decreasing the risk of nephrotoxicity compared with multiple daily dosing. However, ICU patients have pharmacokinetic differences compared with patients who are less ill, including increased volume of distribution and variable clearance, which may make attainment of this target difficult. The need for extended-interval aminoglycoside dosing with Cmax monitoring and MIC determination of the pathogen may be needed to optimally treat serious infections in the critically ill.
Rea
Rhonda S
RS
Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. rhonda_rea@yahoo.com
Capitano
Blair
B
D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016638:Critical Illness / Q000628:therapy; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents