{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:55:36Z","timestamp":1792803336412,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T00:00:00Z","timestamp":1714262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38\/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient\u2019s immune profile to optimize outcomes in sepsis management.<\/jats:p>","DOI":"10.3390\/antibiotics13050406","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T09:50:07Z","timestamp":1714470607000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Interplay between Antibiotics and the Host Immune Response in Sepsis: From Basic Mechanisms to Clinical Considerations: A Comprehensive Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1496-020X","authenticated-orcid":false,"given":"Martina","family":"Tosi","sequence":"first","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Coloretti","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1254-9995","authenticated-orcid":false,"given":"Marianna","family":"Meschiari","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Policlinico di Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"De Biasi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children & Adults, University of Modena, and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2453-0829","authenticated-orcid":false,"given":"Massimo","family":"Girardis","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-4967","authenticated-orcid":false,"given":"Stefano","family":"Busani","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13054-019-2478-6","article-title":"Frequency and mortality of septic shock in Europe and North America: A systematic review and meta-analysis","volume":"23","author":"Vincent","year":"2019","journal-title":"Crit. 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