Delayed time-to-antibiotics may increase 28-day mortality in sepsis patients with respiratory or CV dysfunction

It is already known that sepsis is the leading cause of mortality and morbidity among patients admitted to the ICU. Early antibiotic treatment is recommended to control infection.

The current guideline recommends antimicrobials administrated within 1–3 hours of sepsis recognition, but it remains controversial.

The controversy exists between time-to-antibiotics and clinical outcomes in patients with ICU onset sepsis.

Considering the above background, Wenhan Hu and colleagues from the Department of Critical Care Medicine did a study to determine the questions given below:

What is the association between time-to-antibiotics and the prognosis of patients with ICU onset sepsis?

Which sepsis phenotype poses a high death risk associated with delayed time-to-antibiotics?

The study points include the following:

• The MIMIC-IV database was used to identify patients who had ICU onset sepsis.
• The primary exposure was measured from recognition of sepsis to the first antibiotic administered: time-to-antibiotics.
• Latent profile analysis (LPA) identified phenotypes of sepsis based on individual organ failure scores derived from SOFA (Sequential Organ Failure Assessment).
• Interactions between phenotypes and time-to-antibiotics on 28-day mortality were explored.
• The final analysis had 6246 patients.
• The overall 28-day mortality was 12.7%.
• Delayed time-to-antibiotics increased 28-day mortality with HR 1.12.
• The researchers identified four phenotypes of sepsis:

Phenotype 1: Respiratory dysfunction

phenotype 2: Cardiovascular dysfunction

phenotype 3: Multiple organ dysfunction

phenotype 4: Neurological dysfunction.

• The adjusted HR of 28-day mortality in phenotypes 1 and 2 was 1.16 and 1.06, respectively.

To conclude, Septic patients with respiratory or cardiovascular dysfunction were associated with the harms of delayed time-to-antibiotics.

The phenotypes showed different patterns of organ failure and responded differently to delayed time-to-antibiotics.

The researchers said that our study’s findings indicate that identifying and targeting specific phenotypes of sepsis may be fundamentally crucial for the design of future clinical trials.

Further reading:

Hu, Wenhan, et al. “Identifying High-risk Phenotypes and Associated Harms of Delayed Time-to-antibiotics in Patients With ICU Onset Sepsis: A Retrospective Cohort Study.” Journal of Critical Care, vol. 74, Elsevier BV, Apr. 2023, p. 154221. Crossref,

https://doi.org/10.1016/j.jcrc.2022.154221.