Ex vivo normothermic perfusion (EVNP) of deceased donor kidneys is being used in a growing number of UK centers,1 because there is emerging evidence for its use in organ resuscitation,2 viability assessment,3 and reduction of delayed graft function.4 Although no infectious complications attributable to EVNP have been reported thus far,4 it is possible that the warm perfusate may enhance microbial growth. We sought to determine whether organs become microbiologically contaminated during EVNP. To the best of our knowledge, this is the first report to address contamination during normothermic organ perfusion.
Deceased donor kidneys undergoing EVNP between July 2016 and June 2017 at our unit were included. The perfusion technique has been described previously4 and is performed using strict sterile technique. No antibiotics were given during EVNP. After the kidney had undergone EVNP for 40 minutes, 20 mL of warm perfusate was sampled under aseptic technique and placed in aerobic and anaerobic blood culture bottles containing soybean-casein digest broth 3%. Cold preservation fluid from the organ transport bag was also cultured before kidney EVNP. All recipients received a single dose of intravenous amikacin of 7 mg/kg at induction of anesthesia. Posttransplant infections were prospectively recorded. All positive warm and cold fluid cultures were discussed with microbiology colleagues (C.H., C.v.N.t.P.) and were treated if advised.
Twelve kidneys underwent EVNP and were transplanted into 10 recipients (2 dual transplants). Warm perfusate cultures were not taken from 3 kidneys. Five of the 9 EVNP perfusate cultures (56%) had positive bacterial growth (Table 1). In 4 cases, the organisms were coagulase-negative Staphylococcus species and were not treated. Methicillin-sensitive Staphylococcus aureus was cultured once, and the asymptomatic recipient was treated with intravenous flucloxacillin for 7 days from day 1 postoperatively. Two cold transport fluid cultures had positive growth, but with no consistency with the organisms grown from the EVNP perfusates. None of the EVNP perfusate-cultured organisms were implicated in episodes of recipient infection during the early posttransplant period (Table 1). All 10 patients remain well, with no incidences of infected perinephric collections or early sepsis at follow-up (6-15 months post-EVNP).
These results suggest that there is a high rate of contamination with skin commensals during warm organ perfusion, though this does not appear to be the case in hypothermic machine perfusion.5 The source of these organisms remains largely unknown. Discrepant warm and cold fluid culture results suggest that these organisms do not originate from the retrieval process, but that the organisms are introduced either during EVNP or the culture-taking process.
We acknowledge that the study size is small, making it difficult to be certain of the clinical relevance of skin commensals grown from EVNP cultures. However, the absence of infections with these organisms in recipients during the follow-up period (and in those patients where EVNP cultures were not taken4) is reassuring. This lack of skin commensal-related infection in our recipients may be due to the routine use of antibiotics at the time of organ retrieval and implantation, and the relatively high rate of antibiotic use for other infections posttransplant. The use of antibiotics during EVNP would be an attractive option; however, the pharmacology of antibiotics on EVNP is currently unknown, and this therefore raises the risk of nephrotoxicity. Centers should consider the abovementioned when deciding whether to use antibiotics during EVNP or not. At present, UK centers do not give antibiotics to the kidney during warm perfusion. An ongoing randomized controlled trial of EVNP will provide further safety information on this approach.1
Given the issues raised above, the microbiological safety of other warm organ perfusion techniques should also be investigated. This is particularly important if the duration of warm perfusion is prolonged, because microbial growth may be enhanced.6
1. Hosgood SA, Saeb-Parsy K, Wilson C, et al. Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation. BMJ Open
2. Hosgood SA, Saeb-Parsy K, Hamed MO, et al. Successful transplantation of human kidneys deemed untransplantable but resuscitated by ex vivo normothermic machine perfusion. Am J Transplant
3. Hosgood SA, Barlow AD, Hunter JP, et al. Ex vivo normothermic perfusion for quality assessment of marginal donor kidney transplants. Br J Surg
4. Nicholson ML, Hosgood SA. Renal transplantation after ex vivo normothermic perfusion: the first clinical study. Am J Transplant
5. Jomaa A, Gurusamy K, Siriwardana PN, et al. Does hypothermic machine perfusion of human donor livers affect risks of sinusoidal endothelial injury and microbial infection? A feasibility study assessing flow parameters, sterility, and sinusoidal endothelial ultrastructure. Transplant Proc
6. Kaths JM, Cen JY, Chun YM, et al. Continuous normothermic ex vivo kidney perfusion is superior to brief normothermic perfusion following static cold storage in donation after circulatory death pig kidney transplantation. Am J Transplant