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Objective: To compare clinician documentation of sepsis for infective presentations in the ED against a formal sepsis pathway in the ED and to assess appropriateness of the initial parenteral antibiotic prescription for adult patients in ED. Methods: A retrospective, clinical audit of adult patients who received at least one parenteral antibiotic in ED over a 10‐week period in 2018. Documented initial clinical impression was compared with an approved sepsis pathway. Antibiotic appropriateness was assessed using National Antimicrobial Prescribing Survey definitions. Assessment was carried out by an infectious diseases pharmacist, with input from an infectious diseases physician. Results: Two hundred and nineteen infective presentations were included in the analysis. There was a discordance between the initial documented clinical impression compared with the classification when a sepsis pathway was applied. An initial documented clinical impression of sepsis and septic shock was present in 38 (60.3%) of the presentations compared to 63 presentations when a formal sepsis pathway was applied as a screening tool. There was a significant difference in the proportion of patients in each diagnostic group (infection, sepsis and septic shock) according to documented clinical impression versus sepsis pathway classification (P = 0.0002). There were 386 prescriptions for antibiotics as part of the initial management. Antibiotic appropriateness for the initial prescription was assessed as 63.7% appropriate, 27.2% inappropriate and 9.1% not assessable. Conclusion: Our observations demonstrate that use of a formal sepsis pathway may improve the screening and early diagnosis of sepsis and septic shock and that there is a need for antibiotic prescribing guidance in the ED. [ABSTRACT FROM AUTHOR]