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Background: Central line-associated bloodstream infections (CLABSIs) are a potential complication for home parenteral nutrition (HPN) patients., Aim: We sought to analyse risk factors of developing HPN-related CLABSI and assess CLABSI management in the Australian context., Methods: A retrospective observational cohort study was conducted on 34 adult patients receiving HPN via a central venous catheter (CVC) at a Queensland tertiary referral centre between 2016 and 2023. Patient charts were reviewed, and Kaplan-Meier analysis was employed to determine associations between characteristics and time to CLABSI in the first CVC using Peto-Peto Prentice test., Results: A total of 39 CLABSI episodes occurred in 19 patients. Patients with ≥1 CLABSI used regular opioids more than those without CLABSI (P = 0.016). Fourteen (41%, n = 14/34) patients developed a CLABSI in their first CVC. No patient or line characteristics were found to be predictive of CLABSI in their first CVC. The CLABSI rate was 1.02/1000 catheter days. Most CLABSIs were caused by Enterobacterales (22%, n = 12/55) and Candida sp. (22%, n = 12/55). Empiric antimicrobial therapy was adequate in only 25% (n = 7/28), and the median time to effective antibiotic therapy was 22.7 h (interquartile range 4.8-29.8). There were three successful CVC salvages (8%, n = 3/39)., Conclusions: In this cohort of patients, regular opioid use was associated with increased risk of developing CLABSI. Based on our findings, an empiric antimicrobial regime of vancomycin, cefepime and caspofungin will provide adequate coverage for most HPN-related CLABSIs in Australian IF units with a similar antimicrobial distribution and resistance pattern., (© 2024 Royal Australasian College of Physicians.)