Antimicrobial de-escalation as part of antimicrobial stewardship in intensive care: no simple answers to simple questions—a viewpoint of experts

Abstract

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more components of combination empirical therapy, and/or the change from a broad-spectrum to a narrower spectrum antimicrobial. It is most commonly recommended in the intensive care unit (ICU) patient who is treated with broad-spectrum antibiotics as a strategy to reduce antimicrobial pressure of empirical broad-spectrum therapy and prevent antimicrobial resistance, yet this has not been convincingly demonstrated in a clinical setting. Even if it appears beneficial, ADE may have some unwanted side effects: it has been associated with prolongation of antimicrobial therapy and could inappropriately be used as a justification for unrestricted broadness of empirical therapy. Also, exposing a patient to multiple, sequential antimicrobials could have unwanted effects on the microbiome. For these reasons, ADE has important shortcomings to be promoted as a quality indicator for appropriate antimicrobial use in the ICU. Despite this, ADE clearly has a role in the management of infections in the ICU. The most appropriate use of ADE is in patients with microbiologically confirmed infections requiring longer antimicrobial therapy. ADE should be used as an integral part of an ICU antimicrobial stewardship approach in which it is guided by optimal specimen quality and relevance. Rapid diagnostics may further assist in avoiding unnecessary initiation of broad-spectrum therapy, which in turn will decrease the need for subsequent ADE.

Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics

“…In addition to AMT timing [17], its adequacy is equally important. Patients with septic shock, for example, exhibit higher mortality rates with inadequate empirical regimens [18][19][20][21][22].…”

“…ADE remains a controversial topic, with available literature comprised essentially of observational studies and one small randomized controlled trial (RCT) [18,33]. Although probably safe, selection bias prevails as clinicians apparently resort more to ADE in patients with favorable clinical progress [29].…”

“…Although probably safe, selection bias prevails as clinicians apparently resort more to ADE in patients with favorable clinical progress [29]. Moreover, even the definition of ADE remains unclear and its impact on AMR poorly established [18,33].…”

“…ADE can provide an unjustified sense of security with the assumption that short courses of empirical AMT do not impact AMR [18]. However, the ecological consequences of broadspectrum AMT start within days of first therapeutic courses [36].…”

Antimicrobial de-escalation is part of appropriate antibiotic usage in ICU

“…In an opinion paper, de Waele and coworkers [5] questioned the role of antimicrobial de-escalation (ADE) as one of the important components of antimicrobial stewardship in critically ill patients.…”