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.

Keywords: Antibiotic; Antimicrobial; Antimicrobial resistance; Antimicrobial stewardship; De-escalation; Sepsis.

Fig. 1

Schematic overview of the timeline of antimicrobial therapy including antimicrobial de-escalation, with the pivotal and companion antimicrobial components of the empirical regimen and most common changes within a short antibiotic course for critically ill patients with an infection. ‘Antifungals’ refer to  antimicrobials targeting fungal pathogens, ‘anti-MRSA’ to antimicrobials targeting methicillin-resistant Staphylococcus aureus, ‘anti-difficult to treat pathogens’ to antimicrobials targeting resistance in Gram-negative pathogens, ‘atypical/intracellular targeted’ refers to a second antibiotic commonly prescribed for community-acquired pneumonia, ‘antitoxin effect’ to antimicrobials administered for the suppression of toxin and cytokine production, and ‘synergistic effect’ to  most commonly an aminoglycoside given as combination therapy in patients with septic shock

Fig. 2

Antimicrobial management strategies integrating antimicrobial de-escalation in clinical practice