Antibiotic stewardship in the intensive care unit

Abstract

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.

Figure 1

Pathophysiological changes commonly observed in critically ill patients and their effects on drug concentrations. Reproduced with permission from Elsevier Limited [75]. ECMO, extracorporeal membrane oxygenation; RRT, renal replacement therapy.

Figure 2

Achievement of pharmacokinetic/pharmacodynamic targets in intensive care unit patients according to antibiotics used. Data are expressed as percentage of patients achieving target. Doses for each antibiotic are given as a median. This figure was drawn from data in Table 3 of [5] with permission from Oxford Journals. 50% fT > MIC, free drug concentration maintained above minimum inhibitory concentration of the known or suspected pathogen for at least 50% of dosing interval; 50% fT > 4 × MIC, free drug concentration maintained above a concentration fourfold higher than the minimum inhibitory concentration of the known or suspected pathogen for at least 50% of dosing interval; 100% fT > MIC, free drug concentration maintained above minimum inhibitory concentration of the known or suspected pathogen throughout the entire dosing interval; 100% fT > 4 × MIC, free drug concentration maintained above a concentration fourfold higher than the minimum inhibitory concentration of the known or suspected pathogen throughout the entire dosing interval.

Figure 3

Duration of antibiotic treatment of the first episode in the PRORATA trial, according to infection site. White bars indicate patients included in the control group. Hatched bars indicate patients included in the procalcitonin-guided group. This figure was drawn from data in Table 2 of [37] with permission from Elsevier Limited. CAP, community-acquired pneumonia; PRORATA, Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units; UTI, urinary tract infection; VAP, ventilator-associated pneumonia.