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

Area of Science:

• Transplantation immunology
• Infectious diseases
• Organ preservation

Background:

• Donor infections, particularly with multidrug-resistant bacteria, significantly limit organ utilization for transplantation.
• Effective strategies are needed to manage bacterial contamination in donor organs to improve transplant rates.

Purpose of the Study:

• To evaluate the efficacy of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and static cold storage (SCS), each combined with antibiotics (AB), in eliminating bacterial infections in donor rat kidneys.
• To assess the impact of these preservation methods on the viability and outcomes of transplanted infected kidneys.

Main Methods:

• A rat model was established using kidneys infected with Escherichia coli or carbapenem-resistant Klebsiella pneumoniae (CRKP).
• Infected kidneys were treated with specific antibiotics (cefoperazone-sulbactam for E. coli, tigecycline for CRKP) under HMP, NMP, or SCS conditions.
• Bacterial load was quantified, and transplanted kidneys were assessed for post-transplant outcomes.

Main Results:

• Both HMP+AB and NMP+AB treatments demonstrated significant therapeutic effects in reducing bacterial load compared to SCS+AB.
• CRKP bacterial load was significantly reduced in HMP+AB and NMP+AB groups versus SCS+AB.
• Transplantation of CRKP-infected kidneys preserved with HMP+AB resulted in good post-transplant condition of recipients, unlike the SCS+AB group which led to severe infection and euthanasia.

Conclusions:

• Hypothermic machine perfusion and normothermic machine perfusion combined with antibiotics are effective in reducing bacterial load in infected donor kidneys.
• These machine perfusion strategies hold promise for increasing the utilization of organs from donors with active infections, potentially improving transplant rates.