Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis

Abstract

Objective Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with one-year mortality in pediatric severe sepsis. Design Retrospective observational study. Setting Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013. Patients One hundred sixty patients aged ≤21 years treated for severe sepsis. Interventions None. Measurements and Main Results We tested the association of hourly delays from sepsis recognition to antimicrobial administration with one-year mortality using multivariable Cox and logistic regression. Overall one-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 hours were not associated with one-year mortality. However, increased one-year mortality was evident in patients who received antimicrobials ≤1 hour (aOR 3.8, 95% CI 1.2, 11.7) or >3 hours (aOR 3.5, 95% CI 1.3, 9.8) compared to patients who received antimicrobials within 1-3 hours from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 hour was also associated with increased one-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 hours was not associated with one-year mortality (aOR 2.2, 95% CI 0.5, 11.0). Conclusions Hourly delays to antimicrobial therapy, up to three hours, were not associated with one-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 hour from sepsis recognition was associated with increased one-year mortality should be regarded as hypothesis-generating for future studies.

ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis

“…To our knowledge, this study is the first to examine the potential impact of antibiotic timing on mortality beyond 1 month in adults with sepsis, the largest study (by a factor of 10) to examine mortality beyond hospital discharge, and the first to find a significant association of antibiotic timing and long-term mortality in patients with general sepsis (e- Table 4). 15,[35][36][37][38] Confirmatory findings using different analytic strategies, related but not identical outcomes and measures of exposure, and a dose-response effect indicate that our findings are robust. Beyond buttressing findings from studies using early mortality end points, our results also address the controversy over whether sepsis outcomes only begin to worsen after door-to-antibiotic times exceed a specified threshold.…”

Effects of Delayed Antibiotic Therapy on Outcomes in Children with Streptococcus pneumoniae Sepsis

“…Compared to other time thresholds, we identified that 13.6 h has the best predictive performance for predicting sepsis-related in-hospital mortality. Several studies have reported the relationship between different TTAT cutoffs and mortality in sepsis patients; however, the previously reported TTAT breakpoints were slightly different from that in this study (6)(7)(8)(9)(10). Three studies (6)(7)(8) in adult patients used CART analysis to determine the TTAT breakpoints.…”

“…Weiss et al found that antimicrobial therapy administered Ͼ3 h later correlated with poor outcomes in pediatric sepsis (9). Moreover, Han et al found a 1-year mortality increased in patients who received antimicrobials Յ1 or Ͼ3 h later (10). Therefore, the aim of the present study was to analyze the effects of antibiotic administration times on outcomes in children with S. pneumoniae sepsis and to evaluate an optimal time window for empirical antibiotic administration.…”

Evaluation of a digital triage platform in Uganda: A quality improvement initiative to reduce the time to antibiotic administration

“…In comparison, a recent sepsis care improvement initiative in a North American tertiary care children's hospital decreased the mean time for antibiotic administration from 154 to 114 minutes [31]. In a further study at a resource rich hospital, only 61% of children with severe sepsis or septic shock received IVA in under three hours [32]. As such, the digital triage platform is likely to have a more significant impact in low-resource facilities with less efficient treatment procedures, where chronic overcrowding due to inadequate facilities, personnel, and supplies is common [6].…”