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1) Determine frequency and magnitude of delays in second antibiotic administration among patients admitted with sepsis; 2) Identify risk factors for these delays; and 3) Exploratory: determine association between delays and patient-centered outcomes (mortality and mechanical ventilation after second dose).Retrospective, consecutive sample sepsis cohort over 10 months.Single, tertiary, academic medical center.All patients admitted from the emergency department with sepsis or septic shock (defined: infection, ≥ 2 systemic inflammatory response syndrome criteria, hypoperfusion/organ dysfunction) identified by a prospective quality initiative. Exclusions: less than 18 years old, not receiving initial antibiotics in the emergency department, death before antibiotic redosing, and patient refusing antibiotics.We determined first-to-second antibiotic time and delay frequency. We considered delay major for first-to-second dose time greater than or equal to 25% of the recommended interval. Factors of interest were demographics, recommended interval length, comorbidities, clinical presentation, location at second dose, initial resuscitative care, and antimicrobial activity mechanism.Of 828 sepsis cases, 272 (33%) had delay greater than or equal to 25%. Delay frequency increased dose dependently with shorter recommended interval: 11 (4%) delays for 24-hour intervals (median time, 18.52 hr); 31 (26%) for 12-hour intervals (median, 10.58 hr); 117 (47%) for 8-hour intervals (median, 9.60 hr); and 113 (72%) for 6-hour intervals (median, 9.55 hr). In multivariable regression, interval length significantly predicted major delay (12 hr: odds ratio, 6.98; CI, 2.33–20.89; 8 hr: odds ratio, 23.70; CI, 8.13–69.11; 6 hr: odds ratio, 71.95; CI, 25.13–206.0). Additional independent risk factors were inpatient boarding in the emergency department (odds ratio, 2.67; CI, 1.74–4.09), initial 3-hour sepsis bundle compliance (odds ratio, 1.57; CI, 1.07–2.30), and older age (odds ratio, 1.16 per 10 yr, CI, 1.01–1.34). In the exploratory multivariable analysis, major delay was associated with increased hospital mortality (odds ratio, 1.61; CI, 1.01–2.57) and mechanical ventilation (odds ratio, 2.44; CI, 1.27–4.69).Major second dose delays were common, especially for patients given shorter half-life pharmacotherapies and who boarded in the emergency department. They were paradoxically more frequent for patients receiving compliant initial care. We observed association between major second dose delay and increased mortality, length of stay, and mechanical ventilation requirement.