Who Benefits Most From Early Antibiotics in Sepsis?

May 16, 2024

Written by Joshua Belfer

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In a large multicenter observational cohort of patients with sepsis, the strongest mortality benefit was seen for early antibiotic administration (within 3 hours of arrival to the emergency department) in patients with metastatic cancer and with shock.

Why prove it once when you can prove it three times!
In a group of 273,255 septic patients, the authors assessed 36 patient characteristics (including age, sex, organ dysfunction, and chronic conditions) and their association with mortality benefit from shorter time-to-antibiotics. Using three analytic approaches (because why stop at one! Or two!), the authors found:

Method #1: The series of Poisson regression models showed greater mortality benefit of shorter time to antibiotics in patients with metastatic cancer (5.0% adjusted absolute mortality reduction) and shock (7.0% adjusted absolute mortality reduction).

Method #2: The causal forest model suggested these same groups as having the strongest absolute mortality benefit.

Method #3: The spline analysis showed a steeper increase in mortality in patients with metastatic cancer and shock with longer time-to-antibiotics (meaning earlier antibiotics = lower mortality!). 

Despite being an observational study, the authors used a bevy of granular data to look at factors that are most likely to be associated with early antibiotic benefit. All three methods of analysis suggested similar groups would be impacted by early antibiotics, lending strength to these findings. The mortality reductions are both statistically and clinically significant, showing that there is likely a real-life benefit that can be seen by providing antibiotics early to these specific groups. 

How will this change my practice?

There’s already a plethora of evidence showing the importance of early antibiotics in septic patients. While this article may not change my practice on a patient-to-patient basis – I am still going to give antibiotics as early as possible when I have a patient with sepsis – the results give those involved at a systems level (think quality improvement or performance measure tracking) a starting point for more focused efforts.

Source
Heterogeneity of Benefit from Earlier Time-to-Antibiotics for Sepsis. Am J Respir Crit Care Med. 2024 Apr 1;209(7):852-860. doi: 10.1164/rccm.202310-1800OC. PMID: 38261986; PMCID: PMC10995570.