Antibiotic stewardship in the intensive care unit.
Bottom Line: The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions.The root causes of this problem are multifactorial, but the core issues are clear.Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens.
The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial infections in these critically ill patients, based on pharmacokinetic-pharmacodynamic characteristics, but also improving our ability to avoid administering unnecessary broad-spectrum antibiotics, shortening the duration of their administration, and reducing the numbers of patients receiving undue antibiotic therapy. Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens.
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Mentions: ICU patients’ altered PK secondary to increased volume of distribution and decreased elimination can result in insufficient serum aminoglycosides or β-lactam concentrations (or both) when standard doses are administered, emphasizing the need to carefully monitor peak and trough antibiotic levels when treating resistant pathogens, respectively [5,78,79]. Antibiotic doses for ICU patients derived from other patient groups are likely to be suboptimal because of significant antibiotic PK changes, particularly volume of distribution and clearance. Organ support techniques, including renal replacement therapy and extracorporeal membrane oxygenation, increase PK variability (Figure 1) [80-82]. In a recent prospective study conducted at 64 hospitals worldwide, 20% and 40% of 248 ICU patients receiving β-lactams for infection did not achieve free antibiotic concentrations above their pathogens’ MICs during 50% and 100% (50% and 100% fT > MIC, respectively) of the dosing interval (Figure 2) . Frequently, higher than usually recommended antibiotic doses or continuous or extended infusions (or a combination of these) are needed [5,70,71,73,79,83-85]. Interestingly, use of prolonged infusion appeared to be associated with a significant reduction in mortality and improvement in clinical success when compared with intermittent boluses in a recent meta-analysis of 29 studies (18 randomized controlled trials and 11 observational studies) with a total of 2,206 patients .Figure 1