Evaluating the Role of Antibiotics in Patients Admitted to Hospital With Decompensated Cirrhosis: Lessons From the ATTIRE Trial.

"CONFLICTS OF INTEREST Guarantor of the article: Alastair O'Brien, MD, PhD. Specific author contributions: Databases were created by L.C., R.K., and T.T. and verified by A.O.'B. R.K., T.T., and N.F. performed statistical analyses. A.O.'B. wrote manuscript first draft, with contributions from all authors. Financial support: Funded by the Health Innovation Challenge fund awarded to A.O.'B. (Wellcome Trust and Department of Health and Social Care) HICF reference HICF-R8-439, WT grant number WT102568. Potential competing interests: None to report. Trial registration numbers: ATTIRE trial EudraCT number: 2014-002300-24 and International Standard RCT Number: 14174793. Research Ethics Committee Number: 15/LO/0104.Study HighlightsWHAT IS KNOWN✓ Patients with decompensated cirrhosis are at high risk of hospital-acquired infection (HAI) and in certain circumstances, such as acute variceal hemorrhage, antibiotic prescribing in the absence of an active infection diagnosis is beneficial.✓ However, we face a global crisis of antimicrobial resistance, driven in part by antibiotic overprescribing and reducing unnecessary use is a global priority.WHAT IS NEW HERE✓ Nearly half of the antibiotics prescribed at study entry to the large-scale ATTIRE trial were given to hospitalized patients without a clinical diagnosis of infection.✓ We found no evidence that this approach prevented development of HAI, nor mortality overall, although there may be a benefit in those with a serum white cell count >11.✓ Other analyses found no evidence to support the use of rifaximin to prevent HAI.✓ These data demonstrate an overall lack of efficacy for antibiotic prescribing in the absence of infection to prevent HAI in decompensated cirrhosis, despite this being common practice in the United Kingdom.✓ Considering these data, we suggest that infection guidelines and care bundles should include: (i) Prompt de-escalation or discontinuation of empirically prescribed antibiotics guided by culture sensitivities at 24–48 hours after commencement if no infection and an improving patient. (ii) Restricting prophylaxis use to evidence-based indications. (iii) Greater evidence is needed to recommend rifaximin use to prevent HAI.✓ Finally, our real-world data demonstrate the continued uncertainty around management of infection in decompensated cirrhosis emphasizing the need for further clinical research to identify who might benefit from empirical/prophylactic antibiotic use and improved molecular diagnostic approaches to infection diagnosis."

"Financial support: Funded by the Health Innovation Challenge fund awarded to A.O.'B. (Wellcome Trust and Department of Health and Social Care) HICF reference HICF-R8-439, WT grant number WT102568."