antimicrobial stewardship
Antimicrobial
stewardship in sepsis
The set of initiatives to prescribe the best antimicrobial regime with fewer
side-effects and minimal impact on subsequent resistance is discussed
Elisabeth Esteban
MD PhD
Paediatric Intensive Care
Department, Paediatric
and Neonatal Transport
Team, Institut de Recerca
Hospital Sant Joan
de Déu de Barcelona,
University of Barcelona,
Spain
Ricard Ferrer
MD PhD
Intensive Care
Department,
Hospital Universitario
Vall d’Hebron,
Barcelona, Spain;
CIBER Enfermedades
Respiratorias, Spain;
Shock, Organ Dysfunction
and Resuscitation
Research Group (SODIR),
VHIR, Barcelona, Spain
Respiratorias, Spain;
Shock, Organ Dysfunction
and Resuscitation
Research Group (SODIR),
VHIR, Barcelona, Spain
Sepsis is a life-threatening condition that affects
more than 19 million people each year. 1 Among
the measures to address this problem, the
Surviving Sepsis Campaign (SSC) guidelines
established a set of recommendations, including
early administration of broad-spectrum
antibiotics, preferably within one hour. 2
Combination antibiotic therapy is frequently
required to ensure adequate empiric coverage.
After pathogen isolation or favourable clinical
response, even if negative cultures, empirical
antimicrobials can be narrowed to more specific
agents. The objectives of this de-escalation are
reducing antimicrobial resistance and
diminishing adverse antibiotic events. The
frequency of de-escalation varies among studies.
Mokart et al reported 40% de-escalation in septic
patients in an oncologic intensive care unit (ICU)
without any impact in outcomes. 3 An adequate
empirical antibiotic treatment and the
compliance to guidelines regarding the empirical
anti-pseudomonal antibiotics used in the ICU
were independently associated with frequency of
de-escalation. 3 A number of initiatives to promote
optimal antimicrobial therapy have been
implemented. The ABISS-Edusepsis project
(AntiBiotic Intervention in Severe Sepsis; www.
edusepsis.org), evaluated the impact of a quality
improvement intervention focused on time to
antibiotic in patients with severe sepsis. After the
intervention, time to antibiotic in children was
reduced from 60 (21.2–131.2) to 30 (21.1–60)
minutes (p<0.001). The percentage of
de-escalation was 50% and 48% before and after
the intervention, respectively. 4
The frequency of multidrug resistance is
dramatically increasing around the world. Some
estimates suggest that antimicrobial resistance
could be responsible for 10 million deaths
annually by 2050. 5 The World Health Organization
(WHO) reported more than 50% resistance of
Escherichia coli and Klebsiella pneumoniae to third-
generation cephalosporins and quinolones in
majority of world regions. 6 A distressing increase
in carbapenem-resistant microorganisms, and
extended-spectrum beta-lactamase producers
have been reported. Multidrug-resistant
microorganisms increase mortality, hospital
length of stay and associated costs. 7 This situation
is especially dramatic in sepsis where adequacy of
empirical antibiotic therapy is a determinant of
survival. Several initiatives have been adopted in
order to fight this phenomenon. Governments
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and Health Agencies have adopted policies to
stimulate new antibiotic development and
optimise the use of current agents. Judicious and
optimal use of antimicrobials is the core of these
efforts.
Antimicrobial stewardship
Antimicrobial stewardship (AS) has been defined
as “the optimal selection, dosage, and duration of
antimicrobial treatment that results in the best
clinical outcome for the treatment or prevention
of infection, with minimal toxicity to the patient
and minimal impact on subsequent resistance”. 8
The best antimicrobial was defined by Joseph et al
using the four Ds: “right drug, right dose,
de-escalation and right duration”. 9 We can also
add that the best antimicrobial must have the
minimum adverse effects to the patients and
ideally with fewer costs.
AS implies not only de-escalation (substitute
an initially broad-spectrum antibiotic therapy to
a narrower spectrum regimen) but also
discontinuation, removal of agents in case of
multidrug therapies, or shortening the duration
of treatment.
Even though AS has been recognised as good
practice for clinicians and institutions, its
implementation varies widely in hospitals.
Niederman described how de-escalation strategies
in ventilator-associated pneumonia (VAP) varies
from 23% to 74% and determined some of the
barriers against it. 10 The main obstacles to AS are:
fear that the patient will deteriorate; fear that the
patient could have other microorganisms
different to those isolated; difficulties in cases of
negative cultures; and the lack of local guides to
de-escalation. The real concern for intensivists
taking care of sepsis is whether AS is a safe
practice. This is a relevant question, considering
that curing their patients is their main goal.
There are many tools to make AS a safe practice,
including AS programmes, clinical control,
improvement in microorganism identification
and use of biomarkers to guide decisions.
AS programmes
AS programmes (ASP) have been created to
support health care practitioners in ensuring
appropriate antimicrobial use. Each hospital
should create a team according to their personnel
and budget. There is no rigid way to follow; each
hospital must adapt it to its own needs. The
Centers for Disease Control and Prevention