Non-selective beta-blockers enhance resolution of induced infections in animals and healthcare-associated infections in humans
Healthcare-associated infections (HAIs) pose significant risks, leading to increased morbidity, mortality, and costs, exacerbated by multi-drug-resistant microorganisms. This study aimed to evaluate pharmacological prophylaxis targeting sympathetic reflex control of immunity to mitigate systemic infections, offering a novel approach to combating HAIs. The study included animal experiments and a retrospective analysis of orthopedic surgery patients in Romagna, Italy. Young female pigs were intravenously inoculated with Escherichia coli (E. coli) and divided into two groups: propranolol-treated (non-selective β-blocker; 3 mg/kg; 3x/day orally) and vehicle-treated, starting two days before infection. Parameters such as bacteraemia, serum cytokines, biochemical profile, blood count, lactate, glycemia, and flow cytometry were assessed. Additionally, a retrospective analysis of 92,649 orthopedic surgery hospitalizations (2017-2022) examined the association of non-selective and selective β1-blockers with HAI development using conditional logistic regression. Propranolol-treated pigs exhibited a disinhibited immune response to systemic infection, clearing circulating bacteria much earlier than vehicle-treated animals. The retrospective analysis showed that patients on non-selective beta-blockers had a 71.7% reduced risk of developing HAIs, while those on selective β1-blockers had an 18% higher risk. These findings suggest that targeting sympathetic reflex control of immunity via pharmacological prophylaxis may reduce HAIs in surgical patients.
Authors
- Augusta Zannoni (ORCID: https://orcid.org/0000-0002-2972-4921)
- Tiziana Lazzarotto (ORCID: https://orcid.org/0000-0003-3093-363X)
- Davide Martelli (ORCID: https://orcid.org/0000-0001-6523-9598)
- Paola Rucci (ORCID: https://orcid.org/0000-0002-7704-0831)
- Marco Luppi (ORCID: https://orcid.org/0000-0002-9462-5014)
- Yugeesh R. Lankadeva (ORCID: https://orcid.org/0000-0002-3589-9111)
- Clive Newton May (ORCID: https://orcid.org/0000-0001-8548-3846)
- Roberto Amici (ORCID: https://orcid.org/0000-0002-9692-2215)
- Stefano Ratti (ORCID: https://orcid.org/0000-0002-6258-5345)
- Alberto Elmi (ORCID: https://orcid.org/0000-0002-7827-5034)
- Robin M. McAllen (ORCID: https://orcid.org/0000-0002-7979-5656)
- Matteo Cerri (ORCID: https://orcid.org/0000-0003-3556-305X)
- Domenico Ventrella (ORCID: https://orcid.org/0000-0002-9330-979X)
- Alessandra Occhinegro (ORCID: https://orcid.org/0000-0003-2053-6008)
- Luca Alberti (ORCID: https://orcid.org/0000-0002-7819-4090)
- Maddalena Giannella (ORCID: https://orcid.org/0000-0001-8273-7601)
- Alessandra Cappellini
- Timna Hitrec (ORCID: https://orcid.org/0000-0002-9296-3482)
- Davide Golinelli (ORCID: https://orcid.org/0000-0001-7331-9520)
- Maria Laura Bacci (ORCID: https://orcid.org/0000-0001-6702-5868)
- Domenico Tupone (ORCID: https://orcid.org/0000-0002-4238-1011)
- Patrícia Passaglia (ORCID: https://orcid.org/0000-0001-7351-5222)
- Simona Rosa (ORCID: https://orcid.org/0000-0001-6139-7839)
- Silvia Felici
- Emiliana Piscitiello (ORCID: https://orcid.org/0000-0003-1601-0601)
- Ludovico Taddei (ORCID: https://orcid.org/0000-0002-6405-8119)
- Michael J. McKinley (ORCID: https://orcid.org/0000-0001-6590-8720)
- Pierluigi Viale
Institutions
- University of Pisa (IT)
- Oregon Health & Science University (US)
- The University of Melbourne (AU)
- Universidade de São Paulo (BR)
- Florey Institute of Neuroscience and Mental Health (AU)
- Azienda Unità Sanitaria Locale Della Romagna (IT)
- Azienda USL di Bologna (IT)
- Neurological Surgery (US)
- University of Bologna (IT)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1038/s41598-025-22723-7
- Primary Topic
- Surgical site infection prevention
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Health and Medical Research Council