Delayed Antibiotic Therapy and Organ Dysfunction in Critically Ill Septic Patients in the Emergency Department

Abstract

Background: We investigated the effect of antibiotic timing on outcomes based on changes in surrogate markers of organ failure, including platelet, serum bilirubin, serum creatinine levels, and the PaO₂/FiO₂ (P/F) ratio.

Methods: This was a single-center, retrospective observational study of critically ill septic patients who presented to the emergency department (ED). The study period extended from August 2008 to September 2016. The primary outcomes included changes in platelet, serum bilirubin, serum creatinine levels, and the P/F ratio (δ-platelet, δ-serum bilirubin, δ-serum creatinine, and δ-P/F ratio were calculated as values measured on Day 3; values measured at ED enrollment). A multivariable linear regression model was developed to assess variables related to outcomes (δ-platelet, δ-serum bilirubin, δ-serum creatinine, and δ-P/F ratio).

Results: We analyzed 1784 patients who met the inclusion criteria. The overall 28-day mortality was 14% (n = 256/1784). On multivariable linear regression analysis, the hourly delay in antibiotic therapy was significantly associated with a decrease in δ-platelet count (coefficient, -1.741; standard error, 0.740; p = 0.019), and an increase in δ-serum bilirubin (coefficient, 0.054; standard error, 0.021; p = 0.009). In contrast, it was not associated with δ-creatinine (coefficient, 0.008; standard error, 0.010; p = 0.434) or the δ-P/F ratio (coefficient, -0.797; standard error, 1.858; p = 0.668).

Conclusion: The hourly delay of antibiotic therapy was associated with decreased platelet count and increased serum bilirubin concentration in critically ill septic patients during the first three days of ED admission.

Keywords: antibacterial agents; multiple organ failure; sepsis; septic shock; timing.

Figure 1

Crude 28-day mortality according to the timing of first antibiotic therapy. A total of 1784 patients were analyzed the crude mortality was 14%. The bars represent the proportions of patients who received their first antibiotic therapy within the indicated time period and died within 28 days after presentation to the emergency department. The number represents % (no./total no. of each group).

Figure 2

Kernel density plot of the time to first antibiotic therapy after triage in the emergency department. Overall, the median time to first antibiotic therapy was 2.2 h (interquartile range, 1.5, 3.3).

Figure 3

Changes in the measured parameters according to the timing of first antibiotic therapy. (a) δ-Platelet count, (b) δ-serum bilirubin level, (c) δ-serum creatinine level, and (d) δ- PaO₂/FiO₂ ratio. The δ-platelet count tended to decrease with increasing delays in the first antibiotic treatment after triage in the emergency department. In other words, a longer delay in the first antibiotic therapy led to a greater decrease in the platelet count on day 3. On the other hand, the δ-serum bilirubin and δ-serum creatinine levels on day 3 tended to increase with increasing delays in the first antibiotic therapy. The δ-PaO₂/FiO₂ ratio relatively remained constant. The total number of patients were 1525 for δ-platelet analysis, 1784 for δ-bilirubin, 1604 for δ-creatinine and 1780 for δ-PaO₂/FiO₂ ratio. CI, confidence interval.