Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines
IDSA and Surviving Sepsis Guideline • CID
Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines
IDSA Sepsis Task Force
IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from the IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommendations. Our societies had different perspectives, however, regarding the interpretation of the major studies that informed the guidelines' recommendations, thus leading us to different conclusions and different perspectives on the recommendations. IDSA consequently elected not to endorse the guidelines. IDSA nonetheless hopes to be able to continue collaborating with the Surviving Sepsis Campaign and the Society of Critical Care Medicine to resolve our differences and to develop further strategies together to prevent sepsis and septic shock as well as reduce death and disability from these conditions both nationally and globally.
The 2016 Surviving Sepsis Campaign Guidelines were published
under the auspices of the Society of Critical Care Medicine
(SCCM) and the European Society of Intensive Care Medicine
]. After a great deal of deliberation and discussion
with SCCM, the Infectious Diseases Society of America (IDSA)
reluctantly elected not to endorse these guidelines.
IDSA admires the formidable work the Surviving Sepsis
Campaign has done to improve care and outcomes for patients
with sepsis and septic shock. The Surviving Sepsis Campaign
has raised awareness about sepsis, emphasized the
importance of early recognition, and focused attention on the need
to treat septic patients aggressively and expeditiously with
evidence-based interventions. Nonetheless, IDSA did not agree
with many important aspects of the Surviving Sepsis Campaign
The IDSA’s delegate to the Surviving Sepsis Campaign’s
writing committee discussed these differences of opinion with the
writing committee, the Surviving Sepsis Campaign leadership,
and with the leaders of IDSA and SCCM. Unfortunately, our 2
societies were unable to reach consensus on some of the
guidelines’ pivotal recommendations and their associated explanatory
text within the publication deadline set by the Surviving Sepsis
Campaign and SCCM. Thus, the IDSA decided to withhold its
DISTINGUISHING SEPSIS FROM NONINFECTIOUS
IDSA’s major concern with the guidelines is its failure to
acknowledge the practical difficulties clinicians often face
when trying to diagnose sepsis. It is often unclear whether or
not infection is present and whether or not organ dysfunction
is due to infection. Studies suggest that up to 40% of patients
admitted to intensive care units with a diagnosis of sepsis do
not have an infection and thus do not actually have sepsis [
Hence, the benefits of treating patients who are infected need to
be balanced against the harms of treating patients who at first
appear as if they might have infections but in fact do not.
The Surviving Sepsis Campaign Guidelines do not
differentiate between patients with suspected sepsis and suspected septic
shock. The definitions of sepsis and septic shock have
undergone evolution over the past 15 years, and different documents
continue to use different versions of the definitions, which
can lead to confusion [
]. Unfortunately, none of the
iterations of definitions provides optimal sensitivity or specificity.
However, regardless of which definitions are used for sepsis and
septic shock, conflating suspected sepsis with suspected septic
shock leads to one-size-fits-all recommendations. If there is a
possibility that a patient with shock might have an infection,
it is understandable and appropriate to administer broad
spectrum antibiotics and fluids immediately. Clearly, if the patient
is infected, there is little margin for error. For patients with less
severe disease and in whom the presence of infection is
uncertain, there is often more time to gather additional diagnostic
IDSA and Surviving Sepsis Guideline • CID 2018:66 (15 May) • 1631
data to generate a more informed and precise therapeutic plan.
If the clinician decides that infection is plausible, antibiotics
can and should be administered promptly [
]. In many
cases, however, patients that initially seemed as if they might be
infected turn out to have noninfectious conditions, or infections
that do not benefit from antibacterial agents, for example, viral
infections. Such patients stand only to suffer potential harm
from antibiotics. Moreover, overuse of antibiotics has negative
consequences for hospital populations in general in addition to
the specific patient receiving treatment. This risk is worth
taking for a patient in shock, but we do not believe the risk should
be entered lightly in patients with less severe illness where there
is often time to gather more data before committing the patient
TIME TO INITIATION OF EMPIRIC ANTIBIOTIC
Employers and health plans rightfully turn to professional
guidelines when developing quality measures. Unfortunately
this can become problematic when guideline recommendations
are overly rigid [
]. The Surviving Sepsis Campaign Guidelines
recommend “that administration of IV antimicrobials be
initiated as soon as possible after recognition and within 1 hour for
both sepsis and septic shock (strong recommendation,
moderate quality of evidence; grade applies to both conditions).”
IDSA agrees that antimicrobials should be initiated as soon
as possible to patients with severe infections. We are fearful,
however, that stipulating an aggressive, fixed time period "from
the time of recognition" may lead to unintended consequences,
namely, an increased likelihood that broad-spectrum
antibiotics will be given more frequently to uninfected patients with
syndromes that look like infections in the rush to meet the fixed
frame stipulated for infected patients.
Several of the senior authors of Surviving Sepsis Campaign
Guidelines published an explanatory article regarding the 2016
Surviving Sepsis Campaign Guidelines that states: “First, the
recommendation for antibiotic administration within an hour of
diagnosis of sepsis is a lofty goal of care, judged to be ideal for
the patient but not yet standard care … This is one among
several ‘aspirational recommendations’ considered by the experts to
represent best practice that individual practitioners and healthcare
teams should strive to operationalize” [
]. Of note, other
guidelines or bundles from CMS [
] and Institute for Healthcare Quality
] propose that 3 hours is a reasonable target.
None of these organizations, however, including the
Surviving Sepsis Campaign Guidelines, provide clear guidance
on precisely how to measure adherence. To adhere to best
practices recommended by the guidelines, providers need specific
directions. The guidelines do not define how “time to
antibiotics” is measured in terms of either a starting point or the
endpoint. There are several possible starting points such as time of
first fever documented by vital signs, time of first health care
1632 • CID 2018:66 (15 May) • IDSA Sepsis Task Force
provider contact, time of emergency room admission, time to
positive sepsis screening, time of first documentation of organ
dysfunction, or time of first antibiotic order. Similarly, there are
many possible measured endpoints such as time to initiation
of first antibiotic, time to initiation of all antibiotics, or time to
initiation of appropriate antibiotics. Regulatory agencies might
thus make their own definitions. Individual hospitals might
advertise their quality by making their own easily attained
parameters and showing better performance than comparator
organizations that use more stringent definitions.
We agree in principle with the desirability of “prompt”
administration of antibiotics for documented or suspected
infection. Analogous to hypertension, one might consider sepsis
to be a medical urgency, and septic shock to be a medical
emergency. Unfortunately, however, unlike severe hypertension,
myocardial infarct, or stroke, there is no objective event,
electrocardiogram, or vital sign that would define sepsis or septic
shock with any specificity.
We do think it is feasible and constructive to propose a
recommendation that is easily measured and likely to improve
care, that is, a recommendation that encourages acceleration
of antibiotic delivery. Thus the emphasis would be on
accelerating drug delivery once the clinician makes the decision that
antibiotics are appropriate and writes a stat order and removes
emphasis on recognition that might be interpreted as time of
emergency room registration, time of first fever, etc. Such a
recommendation is supported by observational data: “For patients
with presumed sepsis or septic shock, the administration of each
antibiotic ordered should be initiated promptly, with health care
systems working to reduce that time to as short a duration as
]. We currently would not define whether
“promptly” should be interpreted as 1 hour, 2 hours, 3 hours,
or something else until a comprehensive review by
stakeholders to assess the feasibility of implementation [
]. Thus, for
patients who appear to be in septic shock, the provider would
optimally make a rapid assessment, recognize that starting
antibiotics is an emergency, and signal the healthcare team of this
need by entering a stat order. Pharmacy and nursing in turn
would collaborate to assure that antibiotics are immediately
available and immediately administered, working to reduce the
measured time from order placement to initiation of
administration for each and every antibiotic. For a patient who appeared
to be septic but was not in shock, the provider might choose to
obtain additional or even sequential data to determine if
infection were in fact the inciting cause. If the assessment was that
antibiotics were needed for this medical urgency, the
healthcare team would then ensure that each and every stat antibiotic
ordered was promptly administered.
BLOOD CULTURES AND IV ACCESS CATHETERS
The identification of the organism causing sepsis or septic
shock is obviously an important part of any set of guidelines for
clinicians because such identification is pivotal for
administering optimal therapeutic interventions. For diagnostic tests that
have been in use for many years, a standard approach to
documenting the cause of sepsis or septic shock has been to draw
blood cultures, as well as to perform diagnostic studies on other
appropriate fluids and tissues. The guidelines endorse drawing
at least two blood cultures before starting antimicrobial therapy,
including one blood culture drawn peripherally and one drawn
through an intravenous catheter. This seems eminently
reasonable. However, the information recommending two cultures is
relegated to a bolded “Remark” that is not rated, and
information about drawing blood cultures from a peripheral site plus
one (or all) catheters is buried in subsequent text. The
guidelines do not address whether to draw blood cultures from all
catheters and all lumens, or how to prioritize catheters if there
are multiple catheters and lumens in place. Later in the
document the guidelines provide advice about removing catheters
if such devices are “a possible” source of infection. However, in
a septic patient with a catheter, especially a catheter that has
been in place for several days and used multiple times, isn’t the
catheter always a “possible” source? In addition, clinicians are
given little guidance about tunnel infection, exit infection, or
strategies for removal of implanted or temporary devices. We
think the guidelines should have clearly recommended
removing catheters in patients with refractory shock, hard to treat
organisms, or persistent bacteremia. Readers could be referred
to other sources, but experience suggests that having pivotal
information in one place maximizes the likelihood that such
information will be accessed [
COMBINATION AND MULTIDRUG THERAPY
A major contribution of these guidelines should be advice
on which antimicrobial agents to choose for empiric and for
targeted therapy. The classification and terminology of
antimicrobial therapy (Table 6) in the document is confusing. The
distinction between multidrug and combination therapy is
probably not obvious to either casual readers of the document
or even to those who carefully read Table 6. This table provides
definitions for “empiric,” “targeted/definitive,” “multi-drug,”
and “combination” therapy. These are not widely held
definitions, and their distinction between combination therapy (2 or
more active agents prescribed to accelerate pathogen clearance
rather than to broaden antimicrobial coverage), and
multidrug therapy (therapy with multiple antimicrobials to broaden
coverage for empiric therapy or to accelerate pathogen
clearance, includes combination therapy) would not be obvious to
many readers or even to some experts in the field. In many
sentences that discuss therapy, the term “combination” therapy is
used when, in fact, with their definitions, they should be using
the term “multidrug” therapy.
The guidelines suggest that treating septic shock with 2
antibiotics, both active against a patient’s known pathogens,
for “several days” is likely to be clinically useful. They
recommend continuing combination therapy with 2 active agents
until there is clinical improvement and/or evidence of
infection resolution, regardless of when susceptibility results
return. We do not believe that there are robust data to
support these recommendations [
]. We believe the
available data support the empiric use of 2 agents active against
gram-negative bacilli for empiric treatment of septic shock
in order to increase the chance of having at least one active
agent administered. Once susceptibilities return, however,
and demonstrate that there is at least one active agent with
published evidence for clinical benefit, we believe the
available data suggest there is no evidence to support continuing
2 gram-negative agents as opposed to using one active agent.
Indeed one section of the guidelines advocates “that empiric
antimicrobial therapy be narrowed once pathogen
identification and sensitivities are established and/or adequate clinical
improvement is noted…” only to apparently be contradicted
subsequently: “several days of combination therapy is
biologically plausible and is likely to be clinically useful.”
Indeed, the concept of “combination therapy” as defined in
this document is troubling. The guidelines define
“combination therapy” as multidrug regimens that accelerate pathogen
clearance, inhibit toxin production, or provide
immunomodulatory effects. The evidence for the hypothesis that
“combination therapy” accelerates pathogen clearance is controversial
in situations where a highly susceptible pathogen can be
treated with a single highly active agent. The guidelines cite
an observational propensity-matched analysis and
meta-analysis/meta-regression analyses to support this approach [
], but there were substantial limitations to these 2 studies as
described in details elsewhere . A randomized controlled
] of this strategy, however, showed no benefit of
combination therapy versus monotherapy for patients with sepsis
or septic shock (indeed, there were significantly more adverse
effects and a trend toward higher mortality rates in patients
with septic shock randomized to combination vs
]. From a process perspective, it is also less than
optimal that a rated statement is placed in the text rather than as
a bolded recommendation, even if the recommendation for
combination therapy against a sensitive organism is “a weak
recommendation based on low quality of evidence.”
Multiple statements within the guidelines imply that most
patients with sepsis or septic shock often harbor
antimicrobial resistant pathogens. This is not consistent with the
available evidence and could encourage clinicians to use more
antimicrobial agents than would otherwise be indicated.
Multidrug empiric antibiotic therapy is appropriate for
patients with risk factors for multidrug-resistant organisms
but is not necessarily required upfront for all patients with
sepsis, particularly in hospitals with low levels of
IDSA and Surviving Sepsis Guideline • CID 2018:66 (15 May) • 1633
Biomarkers and molecular tests could be very useful to
establish quickly and accurately whether syndromes are caused by
infection and, in the case of molecular tests, what the causative
organism is and what resistance genes it harbors. The Surviving
Sepsis Campaign Guidelines endorses the use of procalcitonin,
in accordance with other guidelines [
]. Procalcitonin levels
have been shown to rise within 4–6 hours in response to invasive
bacterial infection. However, the Surviving Sepsis Campaign
Guidelines do not provide specific and evidence-based
recommendations that providers can follow. The failure to provide
specific guidance leaves readers with the task of finding another
source to operationalize the recommendation.
The guidelines indicate that procalcitonin “can be used” in
septic patients, but what do the words “can be used” indicate to
the clinician because many tests “can be used.” The issue rather
is “should they be used?” The guidelines also specifically suggest
that procalcitonin is a biomarker that is useful for determining
when to stop antibiotics in patients who have “limited evidence
of sepsis,” a patient population that is not defined. Our
interpretation of the literature is that randomized controlled trials
demonstrate that procalcitonin guidance for duration of antibiotic
therapy is feasible and safe in critically ill patients with infections
]. We are unaware of data supporting the guidelines’
recommendation to use procalcitonin in patients with “limited
evidence of sepsis” even if it were clear what population this refers to.
The recommendations for optimizing pharmacokinetics and
pharmacodynamics are also lacking in specifics. If the Surviving
Sepsis Campaign Guidelines deem that there is evidence that
prolonged dosing administration of certain antimicrobial
agents, for instance, is beneficial, they should indicate to
clinicians how to operationalize such an approach, and they should
distinguish how to administer stat antibiotics (in some cases a
rapid bolus) and how to administer subsequent doses.
The Surviving Sepsis Campaign Guidelines recommend against
“sustained systemic antimicrobial prophylaxis in patients with
severe inflammatory states of noninfectious origin.” This
suggests that “nonsustained” antibiotic courses are indicated. IDSA
recognizes that there are many situations when empiric therapy
is reasonable. However, IDSA believes that if there is no infection,
there is no indication for antibiotic therapy. The Surviving Sepsis
Campaign’s subsequent text suggests that the authors may
actually be referring to infection prevention rather than treatment.
Indeed, elsewhere the guidelines suggest “brief antibiotic
prophylaxis for specific invasive procedures may be appropriate.” We
obviously believe that infection prevention is a critical priority
1634 • CID 2018:66 (15 May) • IDSA Sepsis Task Force
for all hospitals, but it is a large and complex topic that is already
well covered by other dedicated guidelines. The Surviving Sepsis
Campaign Guidelines should either refer to these other Guidelines
or provide a better description of what aspects of infection
prevention and prophylaxis they are referring to.
DURATION OF THERAPY
Lastly, the Surviving Sepsis Campaign recommends treating
most patients with sepsis or septic shock with 7–10 days of
antibiotics. IDSA believes that is an oversimplified approach
and risks treating some infections inadequately and others
excessively. This recommendation contradicts the
preponderance of evidence from randomized controlled trials, systematic
reviews, and guidelines that have shown the safety and efficacy
of shorter therapeutic courses for certain infections: 4 days for
intra-abdominal infections and abscesses with source control
]; 5 days for community-acquired pneumonia [
days or less for nosocomial pneumonia [
35, 42, 43
]; and 7 days
or less for acute pyelonephritis [
]. It is difficult for a
guideline document to give specific advice on duration of therapy
given the complex host and microbial interactions unique to
each patient. We would suggest summarizing treatment
duration considerations and recommendations per condition
rather than trying to establish general recommendations for all
In conclusion, IDSA had multiple substantial disagreements
with the Surviving Sepsis Campaign’s recommendations. We are
disappointed that IDSA and SCCM were unable to resolve these
issues before the Surviving Sepsis Campaign Guidelines were
released. We hope we will be able to collaborate with SCCM
and the Surviving Sepsis Campaign to find common ground for
future guidelines. The IDSA strongly believes that patients and
healthcare providers are best served if professional societies can
speak with one voice on topics that are shared across specialties.
Acknowledgments. Members of IDSA Sepsis Task Force include Andre
C. Kalil, MD, University of Nebraska Medical Center, Omaha, Nebraska;
David N. Gilbert, MD, Providence Portland Medical Center, Portland,
Oregon; Dean L. Winslow, MD, Stanford University Medical Center,
Palo Alto, California; Henry Masur, MD, NiH Clinical Center, Bethesda,
Maryland; Michael Klompas, MD, Harvard Medical School, Boston,
Massachusetts. Dr. Masur represented IDSA on the writing committee for
the Surviving Sepsis Campaign Guidelines section on the diagnosis and
therapy of microbial infections.
Financial support. This research was supported in part by the Intramural
Research Program of the National Institutes of Health Clinical Center.
Potential conflict of interest. No author has a conflict of interest
related to this submission. All authors have submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest. Conflicts that the editors
consider relevant to the content of the manuscript have been disclosed.
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