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.

Highlights

  • 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

  • We investigated the effect of antibiotic timing on the outcomes of sepsis based on changes in surrogate markers of organ failure, including the Sequential Organ Failure Assessment (SOFA) score components of platelet count, serum bilirubin and creatinine levels, and PaO2/FiO2 (P/F) ratio

  • We investigated the impact of antibiotic timing on outcomes assessed based on changes in surrogate markers of organ failure

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Summary

Introduction

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. 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). 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. The Surviving Sepsis Campaign guidelines recommend broad-spectrum antibiotic therapy be initiated as soon as possible, but at least within one hour after the recognition of sepsis or septic shock [4,5]

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