IDSA and SCCM Sepsis Guidelines Controversy: An Expert Perspective

In the commentary below, Stanford T. Shulman, MD, editorial advisory board member for Infectious Disease Advisor, explains why the Infectious Diseases Society of America did not endorse the 2016 Surviving Sepsis Campaign Guidelines.

It is somewhat unusual for academic societies to disagree strongly when they author guidelines that relate to the same medical issue. Guidelines are consensus statements based upon relevant literature; thus, they are expected to review essentially the same studies and very often should reach similar or identical conclusions that lead to very similar recommendations.

Therefore, it is noteworthy that the Infectious Diseases Society of American (IDSA) very recently elected not to endorse the 2016 Surviving Sepsis Campaign Guidelines (SSCG) because of disagreements with the Society of Critical Care Medicine (SCCM) regarding the diagnosis and therapy of those with apparent or documented sepsis or septic shock.¹

The 2016 SSCG were developed by the SCCM and the European Society of Intensive Care Medicine and published in May of 2017.² The major concern of the IDSA Sepsis Task Force is the failure of the SSCG to acknowledge that it is often initially unclear whether or not a patient has sepsis; up to 40% of those admitted to intensive care with a diagnosis of sepsis are not confirmed to have an infection.³ Thus, the benefit of prompt therapy of those infected needs to be balanced by the potential harm of treatment of those initially thought to have possible infections but who do not. The SSCG do not distinguish suspected sepsis from suspected septic shock, and for those patients without shock in whom the presence of infection is unclear, time to acquire additional data often enables development of a more precise treatment plan. If such patients not in shock turn out to have no infection or an infection such as a viral illness that would not benefit from antibiotic therapy, they could suffer harm but receive no benefit from antibiotics. Additionally, it is clear that unnecessary antibiotics are detrimental to the much larger population of society.

The SSCG strongly recommend intravenous antibiotic therapy for suspected sepsis and suspected septic shock as soon as possible and specify that this should be achieved within 1 hour (without defining exactly what that means). The IDSA group agrees with therapy as soon as possible for those with severe infections (presumably with shock) but is concerned that “stipulating an aggressive, fixed time period” may lead to broad-spectrum agents frequently being given to uninfected patients in order to meet a rigid window for therapy. IDSA notes that other relevant guidelines or bundles propose a 3-hour target for therapy. All guidelines are vague regarding how “time to antibiotic “is actually measured. IDSA additionally believes that guidelines should provide clear guidance regarding removal of catheters when relevant for patients with refractory shock, difficult-to-treat organisms, or persistent bacteremia.

The IDSA Task Force also is concerned about the classification of antimicrobial therapy, in that the SSCG refer to “empiric,” “targeted/definitive,” “multidrug,” and “combination” antibiotic therapy in a confusing manner, especially the last 2 terms. Reference to combination therapy (more than 1 active agent to accelerate pathogen clearance rather than broadening the covered bacterial spectrum) and multidrug therapy (more than 1 active agent to broaden empiric coverage or to accelerate pathogen clearance) is not always clear. IDSA is also troubled by the SSCG recommendation to continue 2 active agents until clinical improvement and/or infection resolution, regardless of when susceptibility data are available. IDSA believes that there are no data to support 2 Gram-negative active agents when the organism is susceptible to both, citing a randomized trial that showed no benefit of combination therapy compared to monotherapy for sepsis or septic shock while there were more adverse reactions and a trend toward higher mortality in patients with septic shock randomly assigned to combination therapy.⁴ IDSA also criticizes the SSCG for endorsing the use of procalcitonin levels for diagnosis without providing specific and evidence-based guidance, and also for failure to provide any specifics regarding optimizing antibiotic pharmacokinetics and pharmacodynamics.

Additionally, the IDSA Sepsis Task Force believes that the SSCG suggest that more prolonged systemic prophylaxis is sanctioned for patients with “severe inflammatory states of noninfectious origin,” while IDSA’s view is that if there is no infection, antibiotics are not indicated. Finally, the IDSA group takes issue with the SSCG recommendation to treat most patients with sepsis or septic shock with 7 to 10 days of antibiotics, while many randomized controlled trials, reviews, and guidelines have shown the safety and efficiency of shorter courses of antibiotic treatment. These include 4 days for intra-abdominal infections and abscesses with source control, 5 days for community-acquired pneumonia, and 7 days or less for nosocomial pneumonia or acute pyelonephritis.

The IDSA Sepsis Task Force has expressed its disappointment that IDSA and SCCM could not resolve its areas of disagreement before the SSCG were released, and it hopes for more collaboration for future guidelines. Surely our patients will be advantaged if the relevant professional organizations of experts can reach agreement on important topics that cross specialty lines.

Stanford T. Shulman, MD, is the medical director of Infection Prevention and Control at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Virginia H. Rogers Professor of Pediatric Infectious Disease at the Northwestern University Feinberg School of Medicine​ in Illinois.

References

1. Gilbert DN, Kalil AC, Klompas M, Masur H, Winslow DL. IDSA position statement: why IDSA did not endorse the surviving sepsis campaign guidelines [published online November 22, 2017]. Clin Infect Dis. doi: 10.1093/cid/cix997
2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45:486-552.
3. 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.
4. Brunkhorst FM, Oppert M, Marx G, et al; German Study Group Competence Network Sepsis (SepNet). Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA. 2012;307:2390-2399.