Successful multiple organ donation after donor brain death due to Actinomyces israelii meningitis

The increasing gap between availability of solid organs for transplantation and the demand has led to the inclusion of donor organs that, according to current guidelines, may be discarded, some of them because of the possibility for transmission of infection to the recipients. We present the first report, to the best of our knowledge, of a case of a brain‐dead donor with a localized and treated Actinomyces israelii central nervous system infection who, after a thorough evaluation, provided organs for successful transplant procedures in four recipients. There was no evidence of transmission of infection within a 6‐month follow‐up. Relative contraindications must be individualized in order to expand the number of real organ donors, emphasizing caution in rare causes for brain death in which patients should be thoroughly evaluated for possible donation.     

Transmission of infection to liver transplant recipients from donors with infective endocarditis: lessons learned

Donors not meeting standard criteria, such as those with bacteremia, are now being used in response to the increasing need for organs for transplantation. Recommended strategies to prevent the occurrence of donor‐derived bacteremia include the use of directed antibiotic prophylaxis. However, this approach does not eliminate the risk of infection transmission. Similarly, the management of organ recipients from donors with infective endocarditis (IE) remains uncharacterized. We report 2 cases of donor‐derived bacterial infections in liver transplant recipients despite pathogen‐specific antibiotic prophylaxis. In both instances, the donors had documented IE treated with appropriate antimicrobial therapy and clearance of bacteremia. Recipients had very distinctive clinical outcomes likely related to pathogen virulence and the extent of donor infection. Persistent infection in the transplanted liver should be suspected in organ recipients of a liver from donors with IE, despite the absence of bacteremia at the time of death and organ procurement. For eradication, recipients may require prolonged pathogen‐directed antimicrobial therapy, such as is used for endovascular infections. Prompt recognition of donors with IE, appropriate notification, and prolonged antibiotic prophylaxis are key to reducing the risk of such donor‐derived infections.     

A cluster of donor‐derived Cryptococcus neoformans infection affecting lung,liver, and kidney transplant recipients: Case report and review of literature

Donor‐derived infections (DDIs) are a very rare but potentially devastating complication of solid organ transplantation. Here we present a cluster of proven donor‐derived cryptococcal infection in the kidney, liver, and lung recipients from a single donor. Remarkably, the onset of illness in the kidney and liver recipients occurred more than 8‐12 weeks after transplantation, which is beyond the incubation period previously reported for donor‐derived cryptococcosis. DDI should always be considered in the differential diagnosis of transplant recipients admitted with febrile illness, even when presenting beyond the first month post‐transplant. Communication between reference laboratories, transplant centers, and organ procurement organizations is critical to improve outcomes.     

Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC‐producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC‐producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC‐producing K. pneumoniae. All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.     

Multidrug‐resistant Enterobacteriaceae,Pseudomonas aeruginosa,and vancomycin‐resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients

Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug‐resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended‐spectrum β‐lactamase (ESBL)‐producing and carbapenem‐resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin‐resistant Enterococcus (VRE). These bacteria are common causes of infection in this population and bacteremias caused by these organisms are associated with high mortality rates. Carbapenems remain the treatments of choice for serious infections due to ESBL‐producing Enterobacteriaceae in HSCT recipients. Administration of β‐lactam agents as an extended infusion is associated with improved outcomes in patients with severe infections caused by P. aeruginosa. Older agents used for the treatment of CRE and MDR P. aeruginosa infections, such as polymyxins and aminoglycosides, have major limitations. Newer agents, such as ceftazidime‐avibactam and ceftolozane‐tazobactam have great potential for the treatment of Klebsiella pneumoniae carbapemenase‐producing CRE and MDR P. aeruginosa, respectively, but more pre‐clinical and clinical data are needed to better evaluate their efficacy. Daptomycin dosages ≥8 mg/kg/day are recommended to treat VRE infections in this population, particularly in the setting of increasing daptomycin resistance. Strategies to prevent these infections include strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship. Last, gastrointestinal screening to guide empirical therapy and the use of polymerase chain reaction‐based rapid diagnostics may decrease the time to administration of appropriate therapy for these infections, thereby leading to improved outcomes.     

Donor‐derived strongyloidiasis after organ transplantation in Norway

Strongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto‐infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre‐transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor‐derived Strongyloides infection.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Transmission of viral hepatitis by kidney transplantation: donor evaluation and transplant policies (Part 1: hepatitis B virus)

Abstract: This two-part article discusses serologic testing of prospective donors for viral hepatitis B and C as part of the comprehensive donor evaluation and reviews of the current policies and practices aimed at preventing donor-to-recipient transmission of hepatitis B and C viruses (HBV, HBC). This second part of the review discusses HCV. Organs procured from HCV-infected donors can transmit the virus to their recipients. Because a number of studies have associated infections with HCV with increased morbidity and mortality among renal transplant recipients, it is important to prevent HCV transmission with renal transplantation. The majority of organ procurement organizations (OPOs) perform routine screening of organ donors for antibodies to HCV (anti-HCV). The prevalence of HCV infection among cadaver organ donors, ascertained based on a positive anti-HCV test by ELISA2, varies worldwide between 1.08% and 11.8%. The use of kidneys from donors negative for anti-HCV by ELISA2 carries negligible or no risk of transmitting HCV infection. The use of organs from anti-HCV-positive donors has been restricted to life-saving transplants (heart, liver or lung) by the majority of OPOs worldwide. However, discarding kidneys from all anti-HCV positive donors would lead to unnecessary waste of organs because not all anti-HCV positive donors are infectious. Recently, the policy of unconditional restriction on the use of kidneys from anti-HCV positive donors has been challenged, and transplantation of organs from anti-HCV-positive donors into anti-HCV-positive recipients has been found to be safe. An even better alternative might be a policy of transplanting kidneys from anti-HCV-positive donors only in HCV RNA-positive recipients. However, until more data become available, these two strategies remain experimental treatments.     

Asymptomatic transmission of Treponema pallidum (syphilis) through deceased donor liver transplantation

A 55‐year‐old woman underwent liver transplantation (LT) with a graft from a deceased donor. Mandatory pre‐donation investigations showed positive syphilis serology that was available only after the transplant, with high Treponema pallidum particle agglutination assay titer compatible with donor syphilis infection. Despite the institution of appropriate post‐exposure prophylaxis, the recipient demonstrated latent seroconversion; however, liver graft function improved without evidence of syphilitic hepatitis or other manifestations of the disease. Through this first reported case of asymptomatic transmission of syphilis following LT, we highlight the investigations and treatment strategies for donor‐derived syphilis in liver transplant recipients. This report supplements the existing limited evidence on safe use of infected grafts from syphilitic donors through appropriate post‐exposure prophylaxis.     

Solid organ donation after death from listeria encephalitis: A case report

Despite organ shortage, organs from donors with listeria infections have been discarded for transplantation. We present the first‐reported case of liver transplantation following listeria encephalitis. The patient was admitted with progressing neurological symptoms after an episode of gastroenteritis. Rhombo‐encephalitis was diagnosed, and Listeria monocytogenes was found to be the causative pathogen. Despite proper antibiotic treatment and rapid clearance of bacteremia, he continued to deteriorate and became brain dead, after which organ donation was performed. At procurement, he had been treated with amoxicillin for 9 days. The recipient was treated with pipercillin/tazobactam for 21 days. Besides an anastomotic biliary stricture, necessitating endoscopic dilatation and stenting, further clinical course was uneventful and she is doing well eleven months post‐transplant. Our case suggests that listeria encephalitis is not an absolute contra‐indication to solid organ donation. We suggest that donors should be treated with adequate antibiotics for at least 48h prior to procurement and advocate confirmation of sterile blood cultures as a prerequisite for donation. According to listeriosis guidelines, we suggest that the recipient should be treated with targeted antibiotics for at least 2 weeks. The risk of transmission should, however, always be balanced carefully against the suspected waiting list mortality.     

Organ transplantation from a donor colonized with a multidrug-resistant organism: a case report

The number of intensive care unit patients with infections caused by multidrug-resistant organisms is increasing in most developed countries. We report the case of a deceased multiorgan donor, who was an asymptomatic carrier of carbapenem-resistant Klebsiella pneumoniae (CR-KP) in the respiratory tract, a condition that was not diagnosed before organ harvesting and transplantation. The outcome of the 2 kidney recipients, the liver recipient, and 1 of the lung recipients was uneventful; in particular, no evidence of infection transmission or adverse graft outcomes was noted. The other lung recipient had a complicated postoperative course and, 4 weeks post transplantation, he developed a bacteremic pneumonia with CR-KP from which he subsequently died. These results suggest that, in well defined conditions, organs from donors who are CR-KP positive may be considered for transplantation.     

Cadaveric donor selection and management

The current availability of lung donors is far exceeded by the number of potential transplant recipients who are waiting for an organ. This disparity results in significant morbidity and mortality for those on the waiting list. Although it is desirable to increase overall consent rates for organ donation, doing so requires an intervention to affect societal response. In contrast, increased procurement of organs from marginal donors and improved donor management may be realized through increased study and practice changes within the transplant community. Transplantation of organs from marginal or extended-criteria donors may result in some increase in complications or mortality, but this possibility must be weighed against the morbidity and risk of death risk faced by individuals on the waiting list. The effects of this trade-off are currently being studied in kidney transplantation, and perhaps in the near future lung transplantation may benefit from a similar analysis. Until that time, the limited data regarding criteria for donor acceptability must be incorporated into practice to maximize the overall benefits of lung transplantation.     

The path not taken: social and cultural barriers to thoracic transplantation

Religious beliefs, misperceptions, and distrust of the health care system have been cited as barriers to organ donation or transplantation in minorities. Improved training of hospital staff on donation protocols has been demonstrated to increase consent rates for or-gan donation. Increased interaction of minorities with ethnically appropriate transplant candidates, recipients, and donation or procurement personnel has a positive effect on donor rates. Programs using such practices must be expanded to overcome significant barriers to the transplantation of solid organs. Research into additional ways to improve acceptance of organ transplantation by minorities is needed to increase participation rates.     

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.     

Liver‐specific deceased donor risk indices

In order to assess the quality of the donor liver, procuring surgeons should accurately evaluate not only general donor risk indices, such as donor age, causes of brain death and cold ischemic time, but also consider the specific donor risk indices. In this review, we focus on liver‐specific deceased donor risk indices, including liver steatosis, anti‐hepatitis B core (HBc) positive or hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations. Liver steatosis is strongly associated with poor graft function after liver transplantation. Liver with more than 40–50% macrosteatosis should not be used. However, at present the quantity of fatty livers lack accepted standards. The computerized image analysis programs should be used to automate the determination of fat content in liver biopsy specimens. Liver grafts from anti‐HBc positive donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg) positive or anti‐HBc/anti‐HBs positive recipients. HCV positive allografts free from fibrosis or severe inflammation are a safe option for HCV positive recipients. The procurement team should consider liver biopsy to evaluate these HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate of graft primary non‐functions. Recently, however, some investigators reported the sodium level likely has little clinical impact on post‐transplant liver function. The incidence of hepatic artery variations has been reported to be approximately 30%. To avoid injuries, it is very important to know and identify these variations with precision at the time of organ procurement.     

Organ and tissue procurement in the acute care setting: principles and practice--Part 1

The specialty of organ transplantation has grown tremendously during the past decade. With the advent of cyclosporine, artificial organs, and organ-assist devices, the possibility of suitable patients with end-stage organ disease becoming successful transplant recipients has increased dramatically. Consequently, the need for donor organs has risen. The greatest source of potential organ-tissue donors exists in the acute care setting (ie, emergency departments and intensive care units). To meet the need for this increasing demand, emergency physicians must become familiar with the techniques of procurement. Part 1 defines the problem of procurement and presents financial, historic, organizational, legal, and psychosocial aspects of organ-tissue procurement. A synopsis of brain death concludes the discussion. Part 2 (February 1990) presents aspects of the evaluation, selection, maintenance, and management of the organ-tissue donor. Disease transmission and controversial issues in organ-tissue procurement also are discussed.     

Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety

The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at “high risk” (Centers for Disease Control and Prevention, CDC 1994) or “increased risk” (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single‐center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased‐risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post‐transplant HBV core serologies reverted to negative on re‐testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre‐ and post‐transplant microbiological testing.     

Hepatitis B core antibody‐positive donors in cardiac transplantation: a single‐center experience

Hepatitis B virus (HBV) core antibody (HBcAb)‐positive donors are increasingly utilized in solid organ transplantation. We report a single center's experience in cardiac transplantation with 18 HBcAb‐positive donors. Available follow‐up on recipients of cardiac allografts from HBcAb‐positive donors, including 2 donors with low‐level serum HBV DNA at the time of transplantation, demonstrated no documented donor‐derived HBV transmission.     

Ischemic cholangiopathy after liver transplantation

Orthotopic liver transplantation (OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastomotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or "ischemic cholangiopathy" in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.     

Liver fluke‐infested graft used for living‐donor liver transplantation: case report and review of the literature

Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke‐infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living‐donor liver transplantation (LDLT) with an Opisthorchis felineus‐infested graft, and present a review of the literature. A 6‐month‐old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long‐term follow‐up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.