Sepsis severity, rather than underlying immunocompromise, dictates the clinical urgency of antibiotic administration, highlighting the potential need to prioritize rapid administration based on the presence of septic shock.
In adults receiving emergency care for suspected sepsis, modest antibiotic administration delays increase in-hospital mortality only among those with septic shock. Immune status does not appear to alter this risk. These study findings were published in Clinical Infectious Diseases
Clinicians frequently prioritize rapid antibiotic administration in immunocompromised patients as they often experience more severe infections and poorer clinical outcomes. However, evidence supporting a greater urgency based solely on immune status has remained limited.
Researchers conducted a retrospective cohort study of adults admitted through the emergency departments (EDs) of 9 hospitals within the Mass General Brigham health system between May 2015 and February 2024. They aimed to examine whether the association between time to antibiotic administration and mortality differed according to immune status and the presence of septic shock. Eligible patients had suspected sepsis, defined by blood culture collection, receipt of at least 1 intravenous (IV) antibiotic within 6 hours of ED arrival, and evidence of acute organ dysfunction or septic shock.
These findings suggest antibiotic urgency should be guided primarily by sepsis severity rather than immune competence
The primary endpoint was in-hospital mortality. Primary analyses compared antibiotic administration within 1 to 3 hours vs within the first hour after ED arrival, while secondary analyses evaluated administration within 3 to 6 hours vs within 3 hours among patients without septic shock
The analysis included 39,842 hospitalizations for suspected sepsis, including 20,721 (52.0%) among immunocompetent patients and 19,121 (48.0%) among immunocompromised patients, of whom 2283 (11.9%) were classified as severely immunocompromised. Septic shock was present in 35.1% of hospitalizations. Immunocompromised patients had a greater comorbidity burden than immunocompetent patients, with a median Elixhauser mortality index of 20 vs 6, despite having similar median ages (68 vs 69 years)
The most common immunocompromising conditions were solid malignancies (39.5%), rheumatologic inflammatory diseases (34.7%), hematologic malignancies (17.0%), and transplant-related conditions (11.2%). Median time to IV antibiotic administration was slightly shorter among immunocompromised patients than immunocompetent patients (2.17 [IQR, 1.33-3.35] vs 2.27 [IQR, 1.42-3.37] hours), with the shortest median time observed among patients with severe immunocompromise (1.95 [IQR, 1.25-3.00] hours)
In the overall cohort, receiving antibiotics within 1 to 3 hours rather than within the first hour was associated with increased odds of in-hospital mortality among immunocompetent patients (odds ratio [OR], 1.34; 95% CI, 1.12-1.59). A similar association was not observed among immunocompromised patients overall (OR, 1.08; 95% CI, 0.94-1.25)
When outcomes were analyzed according to sepsis severity, the association between delayed antibiotic administration and mortality was confined to patients with septic shock. Among these patients, antibiotic administration within 1 to 3 hours compared with within the first hour was associated with increased mortality among both immunocompetent (OR, 1.41; 95% CI, 1.12-1.76) and immunocompromised (OR, 1.21; 95% CI, 1.002-1.47) patients
The researchers noted comparable effect estimates among patients with mild to moderate and severe immunocompromise, although the estimates for the severe subgroup were not statistically significant
The researchers found no association between antibiotic timing and mortality among patients with sepsis without shock. Receiving antibiotics within 1 to 3 hours rather than within the first hour was not associated with increased mortality among either immunocompetent (OR, 1.22; 95% CI, 0.93-1.60) or immunocompromised (OR, 0.94; 95% CI, 0.76-1.16) patients. Similarly, delaying antibiotics to 3 to 6 hours compared with administration within 3 hours was not associated with higher mortality among patients without septic shock, regardless of immune status.
Interaction analyses further demonstrated that immune status did not significantly modify the relationship between antibiotic timing and mortality. Instead, sepsis severity emerged as the primary factor influencing the association, with delayed antibiotic administration carrying a higher mortality risk only among patients with septic shock
Sensitivity analyses restricted to patients with microbiologically confirmed or otherwise highly probable infections yielded findings consistent with the primary analyses. When the researchers evaluated the composite outcome of in-hospital mortality or discharge to hospice, however, the associations between delayed antibiotic administration and adverse outcomes were attenuated and no longer statistically significant
Study limitations include the single-health-system design, the heterogeneous immunocompromised cohort, the small number of severely immunocompromised patients, potential misclassification of immune status, residual confounding, and findings that may not apply to hospital-acquired sepsis
“These findings suggest antibiotic urgency should be guided primarily by sepsis severity rather than immune competence,” the researchers concluded
Disclosure: This research was supported by The Agency for Healthcare Research and Quality. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures
Gupta S, Klompas M, McKenna CS, et al.Time to antibiotics and mortality in immunocompromised versus non-immunocompromised patients with suspected sepsis.Clin Infect Dis. Published online July 15, 2026. doi:10.1093/cid/ciag401
