By Dean L. Winslow, MD, FACP, FIDSA

Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University

Dr. Winslow reports no financial relationships relevant to this field of study.

SYNOPSIS: The Infectious Diseases Society of America withheld its support for the Surviving Sepsis guidelines. The general concerns included vagueness and inconsistency in definition of sepsis, “one size fits all” prescription of time to administer antibiotics, lack of clarity around drawing blood cultures through IV catheters, recommendation of combination antibiotics, lack of definition around when to use procalcitonin levels, when and how to use pharmacokinetic and pharmacodynamic data effectively, prolonged antibiotic “prophylaxis,” and duration of therapy.

SOURCE: IDSA Sepsis Task Force. Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA did not endorse the Surviving Sepsis Campaign Guidelines. Clin Infect Dis 2018;66:1631-1635.

An Infectious Diseases Society of America (IDSA) delegate (trained in both infectious disease and critical care medicine) served on the Surviving Sepsis Campaign writing team. Differences of opinion expressed by the IDSA delegate and the IDSA Standards and Practice Guideline Committee ultimately were not accepted by the writing committee and campaign leadership; therefore, the IDSA reluctantly withdrew its support of the new guidelines. Major areas of concern identified by IDSA in the 2016 Surviving Sepsis Campaign guidelines are summarized in the synopsis above.

COMMENTARY

It is clear that the Surviving Sepsis Campaign has done much to raise awareness and improve care and outcomes in patients with sepsis and septic shock. In general, the IDSA representatives (and indeed most of us practicing ID specialists) appreciate the overall goals of these guidelines to recognize sepsis promptly and to treat septic patients aggressively and rapidly with evidence-based interventions. The main points of contention between IDSA and Society of Critical Care Medicine centered on specific recommendations and the interpretation of the studies used to support these recommendations.

Since up to 40% of patients admitted to ICUs with a diagnosis of sepsis do not have an infection,1 the benefits of treating infected patients need to be balanced against the harms of treating patients who are not infected. The new guidelines generally failed to define “sepsis,” “septic shock,” and “suspected sepsis/septic shock” with any degree of sensitivity or specificity. While “septic” patients with likely bacterial infection should receive antibiotics promptly, those patients with likely viral infections or noninfectious causes potentially could be harmed by administration of antibiotics. While the risk of giving antibiotics is worth taking in a patient in shock, patients with less severe illness probably should be evaluated more carefully before being given antibiotics. Our group thought that a good analogy would be to consider “sepsis” like a hypertensive urgency, and “septic shock” like a medical emergency. Similarly, prescribing an exact time interval from initial contact to administration of antibiotics is not strictly evidence-based but should be individualized. It also is not clear from the guidelines at what point the clock starts (first detection of fever, time patient arrived in ED, time of documentation of organ dysfunction, time antibiotic is ordered, etc.).

The guidelines also are vague about recommendations on drawing blood cultures from IV lines what type of line, how to do so without contamination, etc. The guidelines do not provide guidance on management of tunnel tract and exit site infections or infected ports, and do not specifically recommend removal of lines in patients with refractory shock, hard-to-treat organisms, or persistent bacteremia — which we recommended.

The big area we objected to was the guidelines’ unsupported recommendation for “combination antibiotic therapy” in patients with both sepsis and septic shock. The guidelines jumble a lot of terms (empiric, targeted/definitive, multidrug, combination) and do not define them adequately. Particularly troublesome was their definition of “combination therapy” as multidrug regimens, which accelerate pathogen clearance, inhibit toxin production, or produce immunomodulatory effects. For this recommendation to administer combination therapy, the authors of the guidelines cited a largely discredited retrospective propensity-matched analysis. However, randomized controlled trials (including those conducted in patients with neutropenic sepsis) never have shown any benefit of combination therapy. Many of us from IDSA were very concerned that this poorly supported recommendation could lead to excessive use of toxic regimens such as β-lactams + aminoglycosides or regimens likely to lead to Clostridium difficile infection, such as β-lactams + fluoroquinolones.

The new guidelines mention that procalcitonin “could be used” to guide duration of therapy in patients who have “limited evidence of infection.” In reality, there exists robust literature supporting the use of procalcitonin to guide duration of antibiotic therapy in patients both with and without documented infection.

The new guidelines mention using pharmacokinetic and pharmacodynamic data to optimize dosing of antibiotics, yet they provide no specific guidance on how to operationalize pharmacokinetic and pharmacodynamic data.

Although the Surviving Sepsis Campaign guidelines recommend against using “sustained systemic antimicrobial prophylaxis in patients with SIRS of noninfectious origin,” it concerned us that they were recommending “non-sustained antimicrobial prophylaxis” in such patients. We were concerned that this vague and unsupported guidance actually would encourage doctors to use systemic antibiotics to “prevent infection” in ICU patients.

The new guidelines recommend that patients with sepsis or septic shock receive 7-10 days of antibiotics. We were concerned that this blanket recommendation would lead to overtreatment in many cases and undertreatment in others. For example, community-acquired pneumonia can be treated adequately in five days, intra-abdominal infections in four days with source control, yet Staph. aureus bacteremia often will require longer courses.

Finally, although we ultimately did not include this in our article, many of us in IDSA have serious concerns about the Surviving Sepsis Campaign’s “one size fits all” guidance for IV fluid administration in patients with sepsis (not those with true septic shock). Many of us as clinicians have seen first hand the adverse effects of over-resuscitation of non-hypotensive elderly patients, often with impaired diastolic function or renal insufficiency, which has resulted in patients needing BiPap or even intubation because of iatrogenic pulmonary edema.

REFERENCE

  1. Klein Klouwenberg PM, Cremer OL, van Vught LA, et al. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: A cohort study. Crit Care 2015;19:319.