New research suggests that de-escalating patients with community-onset sepsis but no indication of a multidrug-resistant organism (MDRO) from broad-spectrum antibiotic therapy is safe and appropriate.
In a study conducted at 67 hospitals in Michigan and involving nearly 37,000 patients, researchers found that sepsis patients who were de-escalated from antibiotics that provide coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PSA) on day 4 had similar rates of 90-day all-cause mortality as those who were continued on those antibiotics. De-escalation from broad-spectrum antibiotics was also associated with fewer days of antibiotics and shorter hospitalizations.
But the proportion of patients who were de-escalated varied widely across the 67 hospitals, even though the practice is recommended by sepsis management guidelines when no MDROs are identified.
The findings were published yesterday in JAMA Internal Medicine.
The authors of the study say the findings support guideline recommendations and wider use of antibiotic de-escalation when warranted.
Clinical implications of de-escalation unclear
Led by researchers with the Veterans Affairs Ann Arbor Healthcare System and the University of Michigan, the study analyzed data on patients with community-onset sepsis collected from June 2020 through September 2024 at 67 hospitals participating in the Michigan Hospital Medicine Safety Consortium.
The consortium is a statewide quality initiative that aims to improve care for hospitalized patients at risk of adverse events. Their aim was to assess the outcomes of broad-spectrum antibiotic de-escalation compared with continuation.
Early empiric broad-spectrum antibiotics are recommended by the 2021 Surviving Sepsis Campaign Guidelines and have been associated with lower mortality in sepsis patients at risk of MDRO infections. But research suggests only 10% of sepsis patients have MDRO infections, and broad-spectrum antibiotics can increase the risk of patient harms, including Clostridioides difficile infections, and promote the development of antibiotic resistance. That’s why de-escalation to narrower-spectrum antibiotics is recommended when no MDRO is identified.
But the authors note that it’s unclear how often this recommendation is followed in clinical practice and that studies comparing de-escalation with continued use of broad-spectrum antibiotics in sepsis patients have produced mixed results. Some have found de-escalation is associated with improved clinical care and survival, but others have found no impact on mortality and unintended consequences such as more secondary infections.
“As a result, the clinical implications of antibiotic de-escalation in patients with sepsis remain unclear,” they wrote.
Using a target trial emulation framework, which uses observational data to mimic the design of a randomized controlled trial, the researchers conducted two studies. One compared sepsis patients with no signs of MDRO infection who were de-escalated from anti-MRSA therapy on day 4 with those who received continued anti-MRSA therapy. The other compared sepsis patients with no signs of MDRO infection who were de-escalated from anti-PSA therapy on day 4 with those who received continued anti-PSA therapy.
The primary outcome of the study was 90-day all-cause mortality. Secondary outcomes included in-hospital mortality, 30-day mortality, length of hospitalization, and days of antibiotic therapy.
Similar 90-day mortality
Of the 36,924 patients (median age, 71; 50.3% female) hospitalized with community-onset sepsis during the study period, 6,926 (18.8%) and 11,149 30.2%), respectively, were eligible for the target trial emulations evaluating de-escalation of anti-MRSA and anti-PSA antibiotics. Of those patients, 2,993 (43.2%) and 2,493 (22.4%), respectively, were de-escalated from anti-MRSA and anti-PSA coverage on day 4.
After weighting to ensure that patients in the de-escalation and continuation groups were well-balanced, anti-MRSA and anti-PSA de-escalation were associated with similar 90-day mortality as continued broad-spectrum therapy (anti-MRSA odds ratio [OR], 100; anti-PSA OR, 0.98). Anti-MRSA and anti-PSA de-escalation were also associated with fewer days of antibiotics to day 14 (anti-MRSA risk ratio [RR], 0.91; anti-PSA de-escalation RR, 0.91) and shorter length of hospitalization (anti-MRSA RR, 0.88; anti-PSA RR, 0.91). All other secondary outcomes were similar.
“In total, our data lend further evidence suggestive that antibiotic de-escalation is both safe and appropriate in patients hospitalized with community-onset sepsis, bolstering guideline recommendations to do so in clinical practice,” the authors wrote.
Across the 67 hospitals, the proportion of eligible patients de-escalated from broad-spectrum antibiotics varied more than 2-fold (anti-MRSA de-escalation, 27.3% to 61.7%; anti-PSA de-escalation, 6.9% to 37.7%). The authors suggest that the higher proportion of patients de-escalated from anti-MRSA antibiotics could reflect both greater clinical certainty and greater ease of de-escalating from anti-MRSA therapy.
The authors add that prospective randomized studies are needed to better understand the effect of de-escalating specific antibiotic classes.
In total, our data lend further evidence suggestive that antibiotic de-escalation is both safe and appropriate in patients hospitalized with community-onset sepsis, bolstering guideline recommendations to do so in clinical practice.
