{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:05:46Z","timestamp":1792263946119,"version":"4.4.0"},"reference-count":62,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Intensive Care Med"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute liver failure (ALF) is a life-threatening syndrome characterized by abrupt hepatic dysfunction accompanied by systemic inflammatory response and immune dysregulation, resulting in a high susceptibility to infectious complications. In the intensive care unit (ICU) setting, bacterial sepsis and invasive fungal infections represent critical determinants of multiorgan failure, liver transplant eligibility, and patient survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>This narrative review synthesizes current evidence on infectious risk, diagnostic challenges, and antimicrobial management in ALF. The immune response to massive hepatocellular necrosis is initially driven by damage-associated and pathogen-associated molecular patterns, resulting in a sepsis-like hyperinflammatory state. This phase is followed by profound immunoparesis, characterized by impaired innate and adaptive immune responses, which facilitates fbacterial translocation, increases susceptibility to nosocomial infections, and promotes colonization and infection with multidrug-resistant (MDR) pathogens. Infections occur in most ALF patients, yet differentiation between sterile systemic inflammatory response and sepsis remains challenging as fever, leukocytosis, and hemodynamic instability are nonspecific and microbiological cultures frequently yield negative results. Conventional biomarkers primarily reflect hepatocellular injury rather than bacterial infection. Antimicrobial therapy should be individualized based on clinical severity, local epidemiology, and MDR colonization, while accounting for profound pharmacokinetic alterations associated with hepatic failure. In liver transplant candidates and recipients, short-course perioperative prophylaxis and judicious interpretation of MDR screening are pivotal to prevent early postoperative infections without promoting antimicrobial resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Optimizing infection diagnosis, biomarker-guided decision-making, and individualized antimicrobial dosing in ALF, particularly in the peri-transplant ICU setting, is critical for improving patient outcomes and limiting the emergence of MDR pathogens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/08850666261459066","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T13:31:37Z","timestamp":1781098297000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Infections and Antimicrobial Management in Patients With Acute Liver Failure"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-9551","authenticated-orcid":false,"given":"Luca","family":"Cremascoli","sequence":"first","affiliation":[{"name":"Citt\u00e0 della Salute e della Scienza"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-5949","authenticated-orcid":false,"given":"Mattia","family":"Puppo","sequence":"additional","affiliation":[{"name":"Citt\u00e0 della Salute e della Scienza"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-5538","authenticated-orcid":false,"given":"Silvia","family":"Martini","sequence":"additional","affiliation":[{"name":"AOU Citt\u00e0 della Salute e della Scienza"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Toscano","sequence":"additional","affiliation":[{"name":"Ivrea Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Girombelli","sequence":"additional","affiliation":[{"name":"Ospedale SS. Annunziata"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-6577","authenticated-orcid":false,"given":"Francesco","family":"Saglietti","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera S. Croce e Carle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Voza","sequence":"additional","affiliation":[{"name":"Humanitas University-Research Hospital"},{"name":"Department of Biomedical Sciences, Emergency Medicine Residency Program, Humanitas University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Zanza","sequence":"additional","affiliation":[{"name":"University of Rome \u201cTor Vergata\u201d"},{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslava","family":"Longhitano","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00693-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002340"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122632"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0103"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14100718"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000458"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25551"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208937"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.01.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.05.005"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.06.016"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.17687"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02278.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2009.127"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-009-1440-6"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2542-5196(21)00280-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30753-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00652-2"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12324"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.09.006"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.815-823.2004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138566"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191223"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2015.09.025"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4848-3"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-1171-2"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.01.002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181ca4b5b"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.03.011"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0553-z"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/533452"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2011.02.005"},{"issue":"10","key":"e_1_3_3_37_2","first-page":"836","article-title":"Absorption of oral amoxicillin and amoxicillin-clavulanate in patients with short-bowel syndrome","volume":"14","author":"Lomaestro BM","year":"1995","unstructured":"Lomaestro BM, Bailie GR. Absorption of oral amoxicillin and amoxicillin-clavulanate in patients with short-bowel syndrome. Clin Pharm. 1995;14(10):836\u2010842.","journal-title":"Clin Pharm"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh519"},{"issue":"4","key":"e_1_3_3_39_2","first-page":"203","article-title":"Pharmacodynamics of fluoroquinolones in experimental models of infection","volume":"22","author":"Andes D","year":"2003","unstructured":"Andes D, Craig WA. Pharmacodynamics of fluoroquinolones in experimental models of infection. Eur J Clin Microbiol Infect Dis. 2003;22(4):203\u2010211.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"8","key":"e_1_3_3_40_2","first-page":"1136","article-title":"Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [14C]linezolid to healthy human subjects","volume":"29","author":"Slatter JG","year":"2001","unstructured":"Slatter JG, Stalker DJ, Feenstra KL, et al. Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [14C]linezolid to healthy human subjects. Drug Metab Dispos. 2001;29(8):1136\u20101145.","journal-title":"Drug Metab Dispos"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq308"},{"issue":"8","key":"e_1_3_3_42_2","first-page":"333","article-title":"Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects","volume":"48","author":"Dvorchik BH","year":"2004","unstructured":"Dvorchik BH, Arbeit RD, Chung J, et al. Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects. Antimicrob Agents Chemother. 2004;48(8):333\u2010340.","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2005.06.008"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010393342"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv192"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70850-3"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199733010-00005"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis437"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1086\/598327"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.363"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01948-17"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn144"},{"issue":"2","key":"e_1_3_3_53_2","first-page":"575","article-title":"Population pharmacokinetic analysis of anidulafungin in patients with and without hepatic insufficiency","volume":"48","author":"Dowell JA","year":"2004","unstructured":"Dowell JA, Knebel W, Ludden TM, et al. Population pharmacokinetic analysis of anidulafungin in patients with and without hepatic insufficiency. Antimicrob Agents Chemother. 2004;48(2):575\u2010582.","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005276697"},{"issue":"2","key":"e_1_3_3_55_2","first-page":"197","article-title":"Safety, tolerance and pharmacokinetics of amphotericin B lipid complex in healthy men","volume":"36","author":"Bekersky I","year":"2002","unstructured":"Bekersky I, Boswell GW, Hiles R, Fielding RM. Safety, tolerance and pharmacokinetics of amphotericin B lipid complex in healthy men. Ann Pharmacother. 2002;36(2):197\u2010203.","journal-title":"Ann Pharmacother"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ933"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i20.6211"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25532"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.030"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2014.01.012"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12868"},{"issue":"1","key":"e_1_3_3_62_2","article-title":"ESCMID\/EUCIC clinical practice guidelines for perioperative antibiotic prophylaxis in abdominal surgery","volume":"29","author":"European Society of Clinical Microbiology and Infectious Diseases (ESCMID) \/ European Committee on Infection Control (EUCIC)","year":"2023","unstructured":"European Society of Clinical Microbiology and Infectious Diseases (ESCMID) \/ European Committee on Infection Control (EUCIC). ESCMID\/EUCIC clinical practice guidelines for perioperative antibiotic prophylaxis in abdominal surgery. Clin Microbiol Infect. 2023;29(Suppl 1):S1\u2010S71.","journal-title":"Clin Microbiol Infect"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-015-0061-0"}],"container-title":["Journal of Intensive Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08850666261459066","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08850666261459066","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08850666261459066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T07:07:04Z","timestamp":1782371224000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08850666261459066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":62,"alternative-id":["10.1177\/08850666261459066"],"URL":"https:\/\/doi.org\/10.1177\/08850666261459066","relation":{},"ISSN":["0885-0666","1525-1489"],"issn-type":[{"value":"0885-0666","type":"print"},{"value":"1525-1489","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"article-number":"08850666261459066"}}