Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Liu, Han; Peng, Zhang; Yu, Bin; Liu, Zhongzhong; Pan, Li; He, Xiao Shun; Fan, Xiaoli; Wang, Yanfeng

doi:10.1111/ajt.17032

Cited by 13 publications

(8 citation statements)

References 69 publications

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“…Donor infection is not always a contraindication to transplantation 18 , and machine perfusion technology itself is emerging as a mechanism to treat donor infections with targeted antibiotics before transplant. 19 However, severe sepsis in a recipient because of bacterial contamination of a graft that underwent normothermic machine perfusion has recently been reported. 3 Therefore, the significance of these microbial contaminants, and how they should be managed in organs intended for transplant, requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Lau

Dennis

et al. 2023

Transplantation

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Background. Normothermic machine perfusion permits the ex vivo preservation of human livers before transplantation. Long-term perfusion for days-to-weeks provides the opportunity for enhanced pretransplant assessment and potential regeneration of organs. However, this risks microbial contamination and infection of the recipient if the organ is transplanted. An understanding of perfusate microbial contamination is required to inform infection control procedures and antimicrobial prophylaxis for this technology. Methods. We modified a liver perfusion machine for long-term use by adding long-term oxygenators and a dialysis filter. Human livers that were not suitable for transplantation were perfused using a red-cell-based perfusate under aseptic and normothermic conditions (36 °C) with a goal of 14 d. Cephazolin was added to the perfusate for antimicrobial prophylaxis. Perfusate and bile were sampled every 72 h for microbial culture. Results. Eighteen partial human livers (9 left lateral segment grafts and 9 extended right grafts) were perfused using our perfusion system. The median survival was 7.2 d. All organs surviving longer than 7 d (9/18) had negative perfusate cultures at 24 and 48 h. Half of the grafts (9/18) became culture-positive by the end of perfusion. Microbial contaminants included Gram-negative (Pseudomonas species, Proteus mirabilis, Stenotrophomonas maltophilia) and Gram-positive bacteria (Staphylococcus epidermidis, Enterococcus faecalis, and Bacillus species) as well as yeast (Candida albicans). Conclusions. Microbial contamination of perfusate is common during long-term perfusion of human livers with both exogenous and endogenous sources. Enhanced infection control practices and review of targeted antimicrobial prophylaxis are likely to be necessary for translation into the clinical arena.

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Section: Discussionmentioning

confidence: 99%

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Lau

Dennis

et al. 2023

Transplantation

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“…The contamination phase remained unclear in the index case and may have occurred due to a breach of sterility during the rapid organ retrieval from the uDCD donor till the handing of kidney on an open kidney NMP perfusion circuit. A protocol‐driven prophylactic antibacterial cefuroxime in index NMP perfusate might have prevented the growth of commensal bacteria, as supplementation of antibiotics in both hypothermic and normothermic machine perfusate has shown to decrease the load of multidrug‐resistant bacterial in infected kidneys undergoing NMP 12 . Similarly, a standardized approach of continuous application of piperacillin‐tazobactam combined with strict aseptic contact handling, including air contamination sterility led to a sterile porcine liver NMP running for over a week 10 …”

Section: Figurementioning

confidence: 99%

“…A protocol-driven prophylactic antibacterial cefuroxime in index NMP perfusate might have prevented the growth of commensal bacteria, as supplementation of antibiotics in both hypothermic and normothermic machine perfusate has shown to decrease the load of multidrug-resistant bacterial in infected kidneys undergoing NMP. 12 Similarly, a standardized approach of continuous application of piperacillin-tazobactam combined with strict aseptic contact handling, including air contamination sterility led to a sterile porcine liver NMP running for over a week. 10 Literature regarding CPF culture preventing a clinically significant infection in SOTR is divisive.…”

mentioning

confidence: 99%

Does machine perfusion enhance graft contamination risk? Fungal graft arteritis following normothermic machine perfusion of neonatal en‐bloc kidney: A case study

Choudhary

Seth

Singh

2023

Transplant Infectious Dis

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“…Goldaracena et al [ 113 ] reported the possibility of the use, during NMP, of Miravirsen (an antisense miRNA that inactivated miRNA-122) in the induction of resistance to re-infection by hepatitis C virus in pig livers in a transplant setting. Liang et al [ 114 ] inoculated Escherichia coli or carbapenem-resistant Klebsiella pneumoniae in a rat model to investigate if antibiotics combined with static cold storage or hypothermic machine perfusion or NMP could eliminate the bacteria. The use of antibiotics significantly reduced the bacterial load in hypothermic as well as in NMP groups.…”

Section: Surgical Frontiers Of Ex Situ Liver Perfusionmentioning

confidence: 99%

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

et al. 2022

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End-stage liver disease patients undergoing liver transplantation are prone to develop numerous infectious complications because of immunosuppression, surgical interventions, and malnutrition. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80%. The challenges faced in the early post-transplant period tend to be linked to transplant procedures and nosocomial infections commonly in bloodstream, surgical, and intra-abdominal sites. Viral infections represent an additional complication of immunosuppression; they can be donor-derived, reactivated from a latent virus, nosocomial or community-acquired. Bacterial and viral infections in solid organ transplantation are managed by prophylaxis, multi-drug resistant screening, risk assessment, vaccination, infection control and antimicrobial stewardship. The aim of this review was to discuss the epidemiology of bacterial and viral infections in liver transplants, infection control issues, as well as surgical frontiers of ex situ liver perfusion.

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Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Cited by 13 publications

References 69 publications

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers

Does machine perfusion enhance graft contamination risk? Fungal graft arteritis following normothermic machine perfusion of neonatal en‐bloc kidney: A case study

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

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