Long delays in antibiotic therapy associated with increased risk of mortality among children with sepsis: JAMA

Researchers have found in a new study that long delays in antibiotic therapy was associated with increased risk of mortality among children with sepsis. The findings of the study have been published in the Journal of American Medical Association.

Pediatric consensus guidelines recommend administering antibiotics within 1 hour for septic shock and within 3 hours for sepsis without shock. However, there is limited evidence pinpointing the exact time delays that worsen outcomes. This study aimed to determine the specific time point at which delays in antibiotic administration are associated with increased risk of mortality among pediatric sepsis patients.

This retrospective cohort study analyzed data from 51 US children's hospitals participating in the Improving Pediatric Sepsis Outcomes collaborative. The study included patients aged 29 days to less than 18 years who presented with sepsis recognized within 1 hour of ED arrival between January 1, 2017, and December 31, 2021. Researchers used piecewise regression to identify the inflection point for sepsis-attributable 3-day mortality and logistic regression to assess the odds of mortality after adjusting for potential confounders. Data analysis occurred from March 2022 to February 2024.

The study included 19,515 cases with a median age of 6 years (IQR 2-12 years). The median time to antibiotic administration was 69 minutes (IQR 47-116 minutes).

The analysis revealed that the time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes.

Patients who received antibiotics within 330 minutes (19,164 patients) had a 3-day sepsis-attributable mortality rate of 0.5% (93 patients) and a 30-day mortality rate of 0.9% (163 patients).

In contrast, patients who received antibiotics after 330 minutes (351 patients) had a 3-day mortality rate of 1.2% (4 patients) and a 30-day mortality rate of 2.0% (7 patients).

The adjusted odds of mortality were significantly higher for those receiving antibiotics later than 330 minutes, with an odds ratio of 3.44 (95% CI, 1.20-9.93; P = .02) for 3-day mortality and 3.63 (95% CI, 1.59-8.30; P = .002) for 30-day mortality.The study confirms that delays in antibiotic administration beyond 330 minutes are associated with increased mortality in pediatric sepsis patients. These findings align with existing literature indicating the importance of early antibiotic treatment in improving sepsis outcomes. The results underscore the need for prompt recognition and treatment of sepsis in the pediatric population.The study concludes that timely antibiotic administration is crucial for reducing sepsis-attributable mortality in pediatric patients. Delays beyond 330 minutes significantly increase the risk of both 3-day and 30-day mortality. These findings support the urgent need for strategies to ensure rapid antibiotic delivery in pediatric sepsis cases. Further research is necessary to explore whether certain subpopulations, such as those with septic shock or bacteremia, might benefit from even earlier antibiotic administration.

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Lane, R. D., Richardson, T., Scott, H. F., Paul, R. M., Balamuth, F., Eisenberg, M. A., Riggs, R., Huskins, W. C., Horvat, C. M., Keeney, G. E., Hueschen, L. A., Lockwood, J. M., Gunnala, V., McKee, B. P., Patankar, N., Pinto, V. L., Sebring, A. M., Sharron, M. P., Treseler, J., … Workman, J. K. (2024). Delays to antibiotics in the emergency department and risk of mortality in children with sepsis. JAMA Network Open, 7(6), e2413955. https://doi.org/10.1001/jamanetworkopen.2024.13955