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Increased Time to Initial Antimicrobial Administration Is Associated with Progression to Septic Shock in Severe Sepsis Patients
Whiles BB, Deis AS, Simpson SQ. Crit Care Med. 2017; 45: 623-9.
Study Question: Does administration of antimicrobial earlier in patient presentation decrease progression to septic shock?
Study Description: A retrospective cohort of patients with severe sepsis and/or septic shock (identified by ICD-9 diagnosis code) analyzed time to first broad spectrum antimicrobial, defined as an antimicrobial with a broad range of gram-positive and negative coverage as recommended by the surviving sepsis campaign. Patients were excluded if the initial antibiotic administration was greater than 24 hours after emergency department (ED) triage, a hospital-acquired infection developed or required vasopressors within 3 hours of presentation. The primary endpoint was development of shock, defined as requiring vasopressors at 3 or more hours after ED triage.
Results: A final cohort of 3,929 patient encounters were included. Respiratory and genitourinary accounted for the two most common sources of infection. Piperacillin/tazobactam was the most common broad spectrum antimicrobial administered. The median time to initial antimicrobial was 2.76 hours in patients not progressing to shock vs. 3.77 hours in patients progressing to shock (p < 0.001). Every hour delay in antimicrobial administration was associated with an 8.0% increase in progression to shock. Increased time to antimicrobial administration, Charlson comorbidity index, and increased number of infection diagnosis codes were identified on regression analysis as predictors of progression to shock. Increased time to antimicrobial administration was associated with a higher rate of shock development and increased in-hospital mortality (OR 1.05; 95% CI 1.03-1.07). Factors associated with increased time to antimicrobials included Charlson comorbidity index and intra-abdominal infections.
Conclusion(s): Early and broad spectrum antimicrobial administration in patients with sepsis may decrease the progression to shock. Progression to shock was associated with a longer ICU and hospital length of stay and increased mortality.
Perspective: This research highlights the importance of identifying patients with sepsis earlier and timely administration of broad spectrum antimicrobials. The study is limited by lack of data on the appropriateness of the initial antibiotic regimen and serum lactate for application of the Sepsis-3 criteria.