Infection and Prophylaxis During Normothermic Liver Perfusion: Audit of Incidence and Pharmacokinetics of Antimicrobial Therapy.


Type
Article
Change log
Authors
Qureshi, Saeed 
Elliott, Heather 
Noel, Alan 
Swift, Lisa 
Fear, Corrina 
Abstract

BACKGROUND: 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. METHODS: Fluconazole and meropenem (100 mg 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. RESULTS: Following administration of 100 mg fluconazole, levels fell slightly from a median of 24.9 mg/L at 1 h to 22.6 mg/L at 10 h. In contrast, meropenem concentrations fell over time, from a median of 21.8 mg/L at 1 h to 9.4 mg/L at 10 h. There were 4 significant microorganisms grown in the perfusions, including 3 Candida species and an Enterococcus faecium. All the Candida-infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the Enterococcus-infected liver was not transplanted. CONCLUSIONS: 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.

Description
Keywords
32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Digestive Diseases, Prevention, Infectious Diseases, Antimicrobial Resistance, Vaccine Related, Emerging Infectious Diseases, Infection
Journal Title
Transplantation
Conference Name
Journal ISSN
0041-1337
1534-6080
Volume Title
Publisher
Ovid Technologies (Wolters Kluwer Health)
Sponsorship
Blood and Transplant Research Unit in Organ Donation and Transplantation (NIHR203332); NIHR Cambridge Biomedical Research Centre (NIHR203312); Organox Ltd