Plasma Pharmacokinetics of Antimicrobial Agents in Critically Ill Patients

Abstract

Prompt optimal antimicrobial treatment in critically ill patients is mandatory and must be achieved not only in terms of spectrum of activity, but also in terms of exposure at the infection site. Plasma profile of antimicrobial agents may represent a valid surrogate marker of drug exposure and allow to identify the correct dosage for a given drug. However, in the critically ill patients the pharmacokinetic behavior of antimicrobials may be altered by some very peculiar pathophysiological conditions, so that dosages significantly different from those used in clinically stable patients or from those originally studied in healthy volunteers for regulatory purposes may often be needed in order to ensure optimal plasma drug exposure in such population. This is especially true for hydrophilic antimicrobials (aminoglycosides, beta-lactams, glycopeptides, lipopeptides, echinocandins, fluconazole, acyclovir, ganciclovir) whose volume of distribution and clearance may be significantly altered by these conditions. These aspects are particularly relevant in patients with severe sepsis or with septic shock for whom the time for being considered as a special population to be studied apart from the general population has probably come. From the healthcare system perspective, this means that individualization of antimicrobial therapy by means of a real time therapeutic drug monitoring coupled with clinical pharmacological advice should be considered an invaluable tool for optimizing antimicrobial therapy and for the containment of microbial resistance in this setting.

Pharmacokinetics of Caspofungin in Critically Ill Patients on Continuous Renal Replacement Therapy

“…The different extracorporeal clearances that we obtained by estimation from C in Ϫ C out and from S c suggest some absorption of caspofungin by the hemofilter membrane, which, however, had no detectable effect on caspofungin plasma pharmacokinetics. Altered hydration state, hemodynamics, and perfusion during critical illness can affect pharmacokinetics (11,12). Low plasma albumin levels were associated with low caspofungin trough concentrations in patients at a surgical ICU (13).…”

Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis – A randomised placebo-controlled pilot trial

“…In terms of volume of distribution (Vd) and clearance (Cl), remarkable alterations in the pharmacokinetics of antimicrobial agents occur in septic conditions [42]. The capillary leakage and concomitant fluid resuscitation in sepsis lead to expansion of extracellular fluid space, consequently increasing the Vd of hydrophilic antimicrobials [43].…”

“…The capillary leakage and concomitant fluid resuscitation in sepsis lead to expansion of extracellular fluid space, consequently increasing the Vd of hydrophilic antimicrobials [43]. Doxycycline is a highly lipophilic tetracycline antibiotic drug which implies a large Vd for the drug [42,44]. In severe sepsis the expansion of Vd might be of less importance for lipophilic antimicrobials due to rapid redistribution of the drugs from intracellular compartments to the interstitium [43].…”

Personalisierte Pharmakotherapie beim Intensivpatienten

“…Bei hoher Plasmaeiweißbindung kann allerdings eine Hypoalbuminämie die Elimination beschleunigen [21]. Wenn die Leberfunktion beeinträchtigt ist, muss die Dosis hepatisch metabolisierter und eliminierter Substanzen reduziert werden [6-8, 14, 28] [3].…”