Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia

Objectives: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia. Design: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database. Settings: One-hundred twenty-two hospitals in the Veterans Affairs Health System. Patients: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated. Interventions: Time to appropriate antibiotic administration and 30-day mortality. Measurements and Main Results: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02–1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4–2.2%) for every hour that passes before antibiotics are administered. Conclusions: The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock

Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial

Background: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome. Research Question: Will resuscitation guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes? Study Design and Methods: Prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to Emergency Rooms with sepsis associated hypotension and anticipated Intensive Care Unit (ICU) admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors. The protocol included reassessment and therapy as indicated by the PLR result. The control arm received Usual Care. Primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first. Results: In modified-ITT (mITT) analysis including 83 Intervention and 41 Usual Care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37L favoring Intervention arm, 0.65 ± 2.85L Intervention arm vs. 2.02 ± 3.44L Usual Care arm, p=0.021. Fewer patients required renal replacement therapy (5.1% vs 17.5%, p=0.04) or mechanical ventilation (17.7% vs 34.1%, p=0.04) in the Intervention arm compared to Usual Care. In the allrandomized Intent to Treat (ITT) population (102 Intervention, 48 Usual Care) there were no significant differences in safety signals. Interpretation: Physiologically informed fluid and vasopressor resuscitation using passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for septic shock patients compared with Usual Care. Trial Registration clinicaltrials.gov identifier: NCT0283773