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Minerva Anestesiologica 2010 July;76(7):509-24


language: English

Some current issues in the pharmacokinetics/pharmacodynamics of antimicrobials in intensive care

Petrosillo N., Drapeau C. M., Agrafiotis M., Falagas M. E.

1 “L. Spallanzani”, National Institute for Infectious Diseases Rome, Italy; 2 Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; 3 Department of Medicine, Henry Dunant Hospital, Athens, Greece; 4 Department of Medicine, Tufts University School of Medicine, Boston, MA, USA


Infections, particularly those caused by resistant pathogens, are a common cause of morbidity and mortality in critically ill patients. However, the availability of effective antimicrobial agents is limited. Critical illness itself can influence the pharmacokinetic/pharmacodynamic (PK/PD) parameters of antimicrobials by altering their volume of distribution and the rate of their excretion and elimination and by impairing their penetration into tissues. Therefore, when designing a treatment regimen, the intensivist should consider and take advantage of antibiotic PK/PD properties. There is significant but inconclusive evidence that critically ill patients may benefit more when antibiotics with time-dependent action are administered in a continuous/prolonged infusion regimen. On the other hand, aminoglycosides exhibit a concentration-dependent pattern of killing and should be administered at high doses once daily or at extended intervals, and their levels in the plasma should by strictly monitored to avoid both underexposure and toxicity. The problem of antimicrobial resistance now involves agents traditionally considered reliable in that aspect, such as vancomycin. Strict monitoring of vancomycin MIC for methicillin-resistant Staphylococcus aureus and the prudent use of the available alternative agents as well as de-escalation strategies might be reasonable strategies for dealing with this problem.

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