Sepsis occurs when the immune system overreacts to an infection, triggering a chain of events that can lead to tissue damage, organ failure, and death. More than 1.7 million American are treated for sepsis each year, and an estimated 250,000 die from it.
The Centers for Medicare and Medicaid Services (CMS) introduced the Severe Sepsis and Septic Shock Management Bundle (SEP-1) in 2015. SEP-1 is a bundle of measures that includes administration of broad-spectrum antibiotics to all patients with possible sepsis within 3 hours of recognition. Other elements of SEP-1 include rapid infusion of fluid, blood cultures, lactate measurement, vasopressors for fluid-refractory hypotension, and re-evaluation of volume status.
SEP-1 was adopted based on evidence that bundle compliance was associated with lower mortality rates. In 2023, CMS announced it would include SEP-1 as a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing (VBP) program. It based its decision on data that indicated that antibiotic and fluid-focused sepsis bundles were associated with improved patient outcomes. For hospitals to get credit, all elements of the bundle must be implemented.
However, a systematic review and meta-analysis published in February, 2025 in Annals of Internal Medicine, found no evidence that SEP-1 compliance was associated with improved mortality.
Another study published in March 2025 in JAMA Network Open, found that sepsis patients who received care that was noncompliant with the Centers for Medicare and Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) tended to be older, have more comorbidities, and have more complex clinical presentation than those who received compliant care. When those factors were accounted for, SEP-1 compliance was no longer associated with improved mortality.
The JAMA article reported on a retrospective study of adult sepsis patients treated at four academic teaching hospitals in Massachusetts, Iowa, and California from January 2019 through December 2022. The aim of the study was to identify the clinical characteristics of patients who received SEP-1–compliant care versus those who received noncompliant care and to assess the association between SEP-1 compliance and hospital mortality.
The study included 590 patients of whom 335 (56.8%) received SEP-1–compliant care and 255 (43.2%) received noncompliant care. In terms of baseline clinical characteristics, patients in the noncompliant group were more likely to be 65 years and older, to have diabetes, and to have multiple comorbidities than those in the compliant group.
On presentation, patients in the noncompliant group had a higher incidence of septic shock, kidney dysfunction, and thrombocytopenia compared with patients in the compliant group. They also had more nonfebrile presentations, impaired mental status, need for bedside procedures, acute concurrent noninfectious illnesses, and noninfectious illness as the primary factor associated with their presentation.
In the unadjusted mortality analysis, SEP-1 compliance was associated with lower crude mortality rates compared with noncompliance. But there was no statistically significant difference between groups after successively adjusting for demographics and comorbidities, infection source, severity of illness, and clinical markers of complexity.
Adjusting for these confounders, many obtainable only through detailed medical record review, shifted the effect estimate for the association between SEP-1 compliance and mortality from protective to null.
These studies cast serious doubt on the mortality benefit of SEP-1 compliance. They also raise the question of whether hospitals should be penalized for not complying with a one-size-fits-all approach that may not improve outcomes and doesn't account for the complexity of sepsis patients.
Since 2023, The Infectious Diseases Society of American has urged CMS to retire SEP-1 and shift focus to risk-adjusted outcome metrics.
References
Ford JS, etal. The The Effect of Severe Sepsis and Septic Shock Management Bundle (SEP-1) Compliance and Implementation on Mortality Among Patients With Sepsis: A Systematic Review, Annals Intern Med, 2025; https://doi.org/10.7326/ANNALS-24-02426
Rhee C, etal. Complex Sepsis Presentations, SEP-1 Compliance, and Outcomes, JAMA Network Open, March 19, 2025; doi:10.1001/jamanetworkopen.2025.1100