{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:51:41Z","timestamp":1762509101490,"version":"3.41.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>Background.<\/jats:title>\n            <jats:p>Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis. Antibiotics are widely used, but the pharmacokinetics of these agents are unknown as is their efficacy. We wished to assess the perfusate concentrations of the meropenem and fluconazole that we use and to audit the incidence of infection with this antimicrobial therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods.<\/jats:title>\n            <jats:p>Fluconazole and meropenem (100\u2009mg each) were added to the perfusate before NMP began, and serial samples were taken and assayed for drug concentrations. Perfusate cultures were available from 210 of the 242 perfusions performed between February 1, 2018, and April 6, 2023; these were reviewed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results.<\/jats:title>\n            <jats:p>Following administration of 100\u2009mg fluconazole, levels fell slightly from a median of 24.9\u2009mg\/L at 1\u2009h to 22.6\u2009mg\/L at 10\u2009h. In contrast, meropenem concentrations fell over time, from a median of 21.8\u2009mg\/L at 1\u2009h to 9.4\u2009mg\/L at 10\u2009h. There were 4 significant microorganisms grown in the perfusions, including 3 <jats:italic toggle=\"yes\">Candida<\/jats:italic> species and an <jats:italic toggle=\"yes\">Enterococcus faecium<\/jats:italic>. All the <jats:italic toggle=\"yes\">Candida<\/jats:italic>-infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>-infected liver was not transplanted.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions.<\/jats:title>\n            <jats:p>Serious infection is a risk with NMP but appears to be mitigated with a protocol combining fluconazole and meropenem. This combination may not be appropriate in areas where resistance is prevalent. Routine culture of NMP perfusate is essential to identify breakthrough organisms early and enable recipient treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/tp.0000000000004897","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T05:00:32Z","timestamp":1704862832000},"page":"1376-1382","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Infection and Prophylaxis During Normothermic Liver Perfusion: Audit of Incidence and Pharmacokinetics of Antimicrobial Therapy"],"prefix":"10.1097","volume":"108","author":[{"given":"Saeed","family":"Qureshi","sequence":"first","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Elliott","sequence":"additional","affiliation":[{"name":"Antimicrobial Reference Laboratory, Pathology Sciences Building, North Bristol NHS Trust, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Noel","sequence":"additional","affiliation":[{"name":"Antimicrobial Reference Laboratory, Pathology Sciences Building, North Bristol NHS Trust, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Swift","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrina","family":"Fear","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Webster","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Gaurav","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Butler","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."},{"name":"The Cambridge NIHR Biomedical Research Centre and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J. E.","family":"Watson","sequence":"additional","affiliation":[{"name":"The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, United Kingdom."},{"name":"The Cambridge NIHR Biomedical Research Centre and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"R1-20250604","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1097\/TP.0000000000003296","article-title":"Clinical implementation of prolonged liver preservation and monitoring through normothermic machine perfusion in liver transplantation.","volume":"104","author":"Cardini","year":"2020","journal-title":"Transplantation"},{"key":"R2-20250604","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s40472-018-0178-9","article-title":"From \u201cgut feeling\u201d 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