{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:37:27Z","timestamp":1776926247009,"version":"3.51.2"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Despite progress in antibiotic therapy and supportive care, septic shock continues to pose a substantial mortality burden in intensive care units, highlighting persistent limitations in current pathogen-focused treatment approaches. A central issue is the heterogeneity of host immune responses to infection, manifesting as diverse clinical phenotypes\u2014such as immunosuppression and hyperinflammation\u2014that drive variability in outcomes. Thus, evolving the therapeutic paradigm from infection control alone to precise modulation of the host response represents a critical next step for improving prognosis. This perspective article scrutinizes an integrated precision medicine framework that combines multidimensional host endotyping, targeted therapeutic strategies, and real-time monitoring with dynamic feedback. We examine its scientific foundations, potential clinical applications, and implementation pathways, while addressing current challenges and future directions. The goal is to offer a structured perspective and actionable insights to advance individualized management of septic shock.<\/jats:p>","DOI":"10.3389\/fmed.2026.1811347","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:38:15Z","timestamp":1776922695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond antimicrobials: a host-directed precision pharmacotherapy framework for septic shock"],"prefix":"10.3389","volume":"13","author":[{"given":"Xian-zhi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Hongqi Hospital Affiliated to Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-shu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"An","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-kun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kong-lei","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University","place":["Mudanjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s00134-020-06151-x","article-title":"Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis","volume":"46","author":"Fleischmann-Struzek","year":"2020","journal-title":"Intensive Care Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1001\/jama.2017.17687","article-title":"Enhancing recovery from Sepsis: a review","volume":"319","author":"Prescott","year":"2018","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.3389\/fimmu.2018.01511","article-title":"Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome","volume":"9","author":"Hawkins","year":"2018","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"104363","DOI":"10.1016\/j.ebiom.2022.104363","article-title":"Immunopathophysiology of human sepsis","volume":"86","author":"Wiersinga","year":"2022","journal-title":"EBioMedicine"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ccc.2016.12.001","article-title":"Persistent inflammation, immunosuppression and catabolism syndrome","volume":"33","author":"Mira","year":"2017","journal-title":"Crit Care Clin"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1001\/jama.1995.03520360048038","article-title":"Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. 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