Impact of Time to Antibiotics on Mortality in Immunocompromised Patients With Sepsis Syndromes

Introduction: Timely antibiotic administration is a key determinant of sepsis survival and is presumed to be critical in immunocompromised host (ICH) patients. However, robust evidence supporting this assumption is limited.


Methods: We evaluated time-to-antibiotics and inpatient mortality in ICH vs. non-ICH adult patients admitted to 9 US hospitals from 2015-2024 with suspected sepsis, defined by a blood culture order, IV antibiotic, and acute organ dysfunction (initiation of non-invasive or invasive ventilation, lactate >2 and < 4 mmol/L, elevated creatinine or bilirubin, or decreased platelets) or shock (hypotension or lactate ≥4.0 mmol/L). ICH status was defined using diagnosis codes, supplemented with clinical data to define a severe ICH group. We used multivariable logistic regression with administrative and clinical covariates to assess the association between antibiotics administered at 1-3h after ED arrival vs 0-1h after ED arrival on in-hospital mortality, stratified by immune status and sepsis severity.


Results: Among 39,845 adults admitted with suspected sepsis (13,989 with septic shock), 20,721 (52%) were non-ICH and 19,124 (48%) ICH, of whom 3,574 (9.0%) were severe ICH. Crude in-hospital mortality was higher in ICH versus non-ICH patients (11.6% vs 7.7%), including in those with septic shock (18.0% vs 13.1%). Delayed antibiotics (1-3h vs 0-1h) were associated with increased mortality in non-ICH patients with sepsis (OR 1.29, 95% CI 1.08-1.54) but demonstrated a weaker association in mild-moderate ICH (OR 1.13, 95% CI 0.96-1.33) and no association in the severe ICH subgroup (OR 0.97, 95% CI 0.67-1.40). Among patients with shock, delays were associated with increased mortality in non-ICH (OR 1.38, 95% CI 1.1-1.75) and mild-moderate ICH (OR 1.27, 95% CI 1.02-1.57) but not in severe ICH (OR 0.95, 95% CI 0.51-1.78).


Conclusions: We observed a stepwise reduction in the mortality risk associated with delayed antibiotics across non-ICH, mild-moderate ICH, and severe ICH patients with sepsis and septic shock. These findings challenge the assumption that timely antibiotics are universally more critical in ICH patients and support a more nuanced approach that balances treatment urgency with diagnostic accuracy in this complex population.