Delayed Antimicrobial Therapy Increases Mortality and Organ Dysfunction Duration in Pediatric Sepsis*

Abstract

Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

“…Moreover, hospital mortality, often considered to be too low to practically study in pediatric severe sepsis, was 25% and exceeded prior epidemiological estimates that relied on retrospective administrative data (1,4,43). As in other studies, comorbid conditions were common (1,5,6,18,(44)(45)(46), and children with immunosuppressive conditions and preexisting renal disease exhibited the highest mortality. However, we could not determine whether death was attributable to sepsis or to an underlying comorbid Definition of abbreviations: ECMO = extracorporeal membrane oxygenation; G/GM-CSF = granulocyte/granulocyte-monocyte colony-stimulating factor; IVIG = intravenous immunoglobulin; RRT = renal replacement therapy.…”

“…This finding suggests that sepsis improvement efforts, which have overwhelmingly focused on the ED setting, may need to be expanded in scope (12,13,45). For example, a prior study demonstrated that antimicrobial administration took .1 hour longer for pediatric patients receiving initial sepsis therapy on a hospital ward than in the ED, with delayed antimicrobial administration independently associated with mortality (46). Our data support the need to better attend to patients with severe sepsis that develops during hospitalization, as this population represents a large proportion of critically ill children with severe sepsis who are more likely to have comorbidities and may face barriers to sepsis recognition and management distinct from those of ED patients.…”

“…However, these studies used International Classification of Diseases, Ninth Revision (ICD-9), codes, which have been shown to capture a lower severity of illness and thereby underestimate mortality (5,7). In a recent database study using expanded ICD-9 coding, researchers reported a PICU mortality of 26.4% (6), and authors of prospective studies have reported short-term mortality rates up to 24% (2,5,19,46,47). The mortality in the present study also reflects the high rate of multiorgan dysfunction.…”

Dose optimization of piperacillin/tazobactam in critically ill children

“…33 Based on these simulations, fT>MIC and fT>CT were calculated for the first 48 hours of treatment, as early and appropriate therapy is most critical. 34 The target efficacy exposure for piperacillin was defined as 60% fT>MIC and PTA was calculated for MICs between 1 to 64 mg/L. 16 (Figure 1A-B).…”

Rapid Detection of Vancomycin-Intermediate Staphylococcus aureus by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

“…elayed initiation of appropriate antibiotic therapy results in increased mortality rates for patients with sepsis (1)(2)(3)(4)(5)(6). Staphylococcus aureus is a pathogen frequently isolated from patients with sepsis, with worse clinical outcomes noted for patients with methicillin-resistant S. aureus (MRSA) (7).…”