Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics
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REVIEW
Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics Patrı´cia Moniz . Luı´s Coelho . Pedro Po´voa
Received: September 22, 2020 / Accepted: October 31, 2020 Ó The Author(s) 2020
ABSTRACT The high prevalence of infectious diseases in the intensive care unit (ICU) and consequently elevated pressure for immediate and effective treatment have led to increased antimicrobial therapy consumption and misuse. Moreover, the emerging global threat of antimicrobial resistance and lack of novel antimicrobials justify the implementation of judicious antimicrobial stewardship programs (ASP) in the ICU. However, even though the importance of ASP is generally accepted, its implementation in the ICU is far from optimal and current evidence regarding strategies such as de-escalation remains controversial. The limitations of
clinical guidance for antimicrobial therapy initiation and discontinuation have led to multiple studies for the evaluation of more objective tools, such as biomarkers as adjuncts for ASP. C-reactive protein and procalcitonin can be adequate for clinical use in acute infectious diseases, the latter being the most studied for ASP purposes. Although promising, current evidence highlights challenges in biomarker application and interpretation. Furthermore, the physiological alterations in the critically ill render pharmacokinetics and pharmacodynamics crucial parameters for adequate antimicrobial therapy use. Individual pharmacokinetic and pharmacodynamic targets can reduce antimicrobial therapy misuse and risk of antimicrobial resistance.
Keywords: Antimicrobial stewardship; Biomarkers; De-escalation; Pharmacodynamics; Pharmacokinetics P. Moniz L. Coelho P. Po´voa (&) Polyvalent Intensive Care Unit, Sao Francisco Xavier Hospital, CHLO, Lisbon, Portugal e-mail: [email protected] L. Coelho P. Po´voa Nova Medical School, CHRC, New University of Lisbon, Lisbon, Portugal P. Po´voa Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Odense, Denmark
Adv Ther
Key Summary Points Antimicrobial stewardship program implementation remains suboptimal in the intensive care setting, where frequent prescription of broad-spectrum antimicrobial therapy and its misuse pose significant risk of antimicrobial resistance, adverse effects, and economic burden. Biomarkers can be considered promising adjuncts for antimicrobial stewardship but knowledge of their strengths and limitations is key to avoiding misinterpretation and misuse. Procalcitonin-guided therapeutic decisions have been linked to decrease in antimicrobial therapy duration; however, no clear mortality benefit has been found. Procalcitonin study limitations such as low protocol adherence, high risk of bias, and longer antimicrobial therapy duration in non-procalcitonin groups call for future well-structured trials. Modified pharmacokinetics in the critically ill, such as augmented renal clearance and increased volume of distribution, p
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