Medico Pediatra

Antibiotic De-Escalation
Robert G. Masterton,
KEYWORDS  De-escalation  Antimicrobial streamlining  Antimicrobial stewardship
FRCPath, FRCP [Edin & Glas]

The present topography of clinical sepsis is a landscape populated by increasing and developing antimicrobial resistance, with a future where ever fewer new antibiotics, particularly innovative classes,1 are becoming available to meetthese challenges. This prospect has resulted in a new focus on making the best use of the antibiotics available to maximize their clinical impact and longevity. Such initiatives have become condensed into 2 main themes that are integrated, with the new treatment paradigm that deals with serious sepsis, of “hit it hard and hit early”2 being embedded within the overall encompassing concept ofantimicrobial stewardship.3 De-escalation forms one of the key features of the new treatment paradigm (Box 1). Within this paradigm de-escalation presents probably the most challenging element. Notwithstanding this, the literature shows that de-escalation has received widespread support in various review and recommendation documents4–6 over the last decade, but in a manner that perhaps does not reflectits true standing against the difficulties attendant to its implementation. Whereas its step-down concept of changing to a more targeted antibiotic is intrinsically logical, in clinical practice it faces the natural instinct of the clinician to continue with a treatment that is proving to be effective in managing the often life-threatening infection affecting a patient. This remains true,notwithstanding the positive conclusion reached within the recently released guidelines on antimicrobial stewardship3 stating that: “Streamlining or de-escalation of empirical antimicrobial therapy on the basis of culture results and elimination of redundant combination therapy can more effectively target the causative pathogen, resulting in decreased antimicrobial exposure and substantial cost savings.”Crucially, whereas the strength of this recommendation was assigned the top rating of an “A”, it was acknowledged that the quality of the clinical evidence underpinning this was only in the middle band. This article therefore reviews the issue of de-escalation to present the current position.

Financial disclosures and/or conflicts of interest: The author has nothing to disclose against thesubject matter and materials discussed in this article. Funding support: None. Department of Microbiology, Ayrshire & Arran NHS Board, The Ayr Hospital, Dalmellington Road, Ayr KA6 6DX, UK E-mail address: robert.masterton@aaaht.scot.nhs.uk Crit Care Clin 27 (2011) 149–162 doi:10.1016/j.ccc.2010.09.009 criticalcare.theclinics.com 0749-0704/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved.150

Masterton

Box 1 Key principles of the new treatment paradigm  Get effective antibiotic selection right first time  Base antimicrobial selection, both empiric and targeted, on knowledge of local susceptibility patterns  Use broad-spectrum antibiotics early  Optimize the antibiotic dose and route of administration  Administer antibiotics for the shortest possible duration AND Adjust or stop antibiotic therapy as early as possible to best target the pathogen(s) and remove pressure for resistance development (ie, de-escalation)

DEFINITION OF DE-ESCALATION

The definition of antimicrobial de-escalation is that it is a mechanism whereby the provision of effective initial antibiotic treatment, particularly in cases of severe sepsis, is achieved while avoidingunnecessary antibiotic use that would promote the development of resistance. This definition therefore encompasses 2 key features. First, there is the intent to narrow the spectrum of antimicrobial coverage depending on clinical response, culture results, and susceptibilities of the pathogens identified, and second, there is the commitment to stop antimicrobial treatment if no infection is established.7...