Delays to Antibiotics and Mortality Risk in Children With Sepsis

Source: Lane RD , Richardson T , Scott HF , et al . Delays to antibiotics in the emergency department and risk of mortality in children with sepsis. JAMA Netw Open. 2024;7(6):e2413955; doi: 10.1001/jamanetworkopen.2024.13955.Investigators from multiple institutions conducted a retrospective study to identify a time point in delay of antibiotic administration for children with sepsis that was associated with an increased risk for mortality. For the study, they reviewed data collected by the Children’s Hospital Association’s Improving Sepsis Outcomes (IPSO) quality improvement collaborative. The IPSO database includes information on pediatric patients treated for sepsis at 57 children’s hospitals in the US. For the current study, data on children 29 days to <18 years old who presented to a participating hospital between 2017 and 2021, met predetermined criteria for sepsis, and in whom sepsis was recognized within 1 hour after presentation to the emergency department (ED) were included in the analyses. The time of sepsis recognition was included in the database and based on initiation of specific processes of care. Data abstracted from the IPSO database included demographic and clinical information, time of recognition of sepsis, time of first administration of antibiotics, and outcome. For patients in the database who died, standardized procedures were used to determine whether the death was related to the index sepsis event. The primary study outcome was sepsis attributable 3-day mortality, and the main secondary outcome was sepsis-attributable 30-day mortality. The main exposure was delay in antibiotic administration, defined as the duration between time of sepsis recognition and time of antibiotic administration. Nonlinear piecemeal logistic regression was used to identify the time point at which delay in antibiotic administration was associated with a significant increase in risk of sepsis-attributable 3-day mortality. Regression analyses also were used to evaluate risk of sepsis-attributable 3- and 30-day mortality associated with antibiotic administration delay beyond the identified time point, after adjusting for confounders.Data on 19,515 cases of sepsis from 51 hospitals were included in the analysis. The median age of study patients was 6 years, and median delay in antibiotic administration was 69 minutes. Overall sepsis attributable 3-day mortality was 0.5% (97 children) and 30-day mortality was 0.9% (170 children). The risk of sepsis-attributable 3-day mortality increased after a delay in antibiotic administration of 330 minutes (P = 0.01). Among 351 patients with a delay of ≥330 minutes, the sepsis-attributable 3-day mortality was 1.2%, compared to 0.5% in 19,164 children in whom the delay was <330 minutes (adjusted odds ratio [aOR], 3.44; 95% confidence interval [CI], 1.20, 9.93). Sepsis-attributable 30-day mortality also was significantly increased for those with a delay ≥330 minutes (2.0% vs 0.9% for those with delays <330 minutes; aOR, 3.63; 95% CI, 1.59, 8.30).The authors conclude that a delay in administration of antibiotics of ≥330 minutes in children with sepsis was associated with an increased risk of death at 3 and 30 days.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Sepsis is a leading cause of death in children worldwide.1 The first step in the management of a child with sepsis is recognition of the condition. The US children’s hospitals participating in the current study were part of a quality improvement learning collaborative that focused on improving the recognition, diagnosis, and treatment of sepsis.2 They included screening, a structured clinical assessment, and a team-based discussion to identify cases of possible sepsis. Next, they used continuous cardio-respiratory monitoring, ongoing assessments, and specific order sets. These measures all contributed to the median time to antibiotic administration of 69 minutes. They intentionally limited the cohort to children who were recognized to have sepsis within the first hour of arrival to the ED to minimize confounding by delayed recognition.3 These characteristics of the study need to be considered in generalizing results.The time of 330 minutes at which mortality increased is longer than current recommendations4 and differs from the results of previous studies5 (see AAP Grand Rounds. 2021:45[4]:41)6 that reported higher odds of mortality when antibiotics were administered beyond 1 hour from sepsis recognition. This difference may be explained by the investigators’ use of broad IPSO sepsis definitions,2 which likely included children who were less severely ill, and the limitation to children whose sepsis was recognized early, and therefore, often prior to clinical deterioration.3In the subgroup analysis of children who received antibiotics within the first 29 minutes, mortality was higher compared with those who received antibiotics at 30 to 329 minutes. This result may seem paradoxical. However, the likely explanation is that children receiving antibiotics earlier were more critically ill, and despite prompt antibiotics, they still manifested higher mortality rates.3Among pediatric patients, prompt recognition of sepsis and initiation of antibiotics reduce the risk of mortality.2