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.     

Toxoplasmosis in non‐cardiac solid organ transplant recipients: A case series and review of literature

The risk of toxoplasmosis in high‐risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post‐transplant chemoprophylaxis in high‐risk (D+/R?) cardiac transplant patients. In contrast, until recently, there have been neither well‐defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non‐cardiac solid organ transplant recipients. We report 3 cases of post‐transplant toxoplasmosis in non‐cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor‐derived. Not surprisingly, pre‐transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30‐120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%).     

Late primary cytomegalovirus infection presenting with acute inflammatory demyelinating polyneuropathy in a heart transplant recipient: a case report and review of the literature

Cytomegalovirus (CMV) infection is well recognized as a cause of morbidity and mortality in heart transplant recipients. Primary CMV infection can occur early post transplant in at‐risk recipients with donor‐derived infection, or any time after transplantation in community‐acquired infection. We describe a unique case of primary CMV infection occurring 14 years after cardiac transplantation. In addition to end‐organ CMV disease, this patient developed a post‐infectious neurologic phenomenon, acute inflammatory demyelinating polyneuropathy. This entity has rarely been reported in the solid organ transplant population.     

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991–92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community‐acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre‐intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high‐risk solid organ transplant patients.     

The deceased organ donor with an “open abdomen”: proceed with caution

In solid organ transplantation, the disparity between donor supply and patients awaiting transplant continues to increase. The organ shortage has led to relaxation of historic contraindications to organ donation. A large percentage of deceased organ donors have been subjected to traumatic injuries, which can often result in intervention that leads to abdominal packing and intensive care unit resuscitation. The donor with this “open abdomen” (OA) presents a situation in which the risk of organ utilization is difficult to quantify. There exists a concern for the potential of a higher risk for both bacterial and fungal infections, including multidrug‐resistant (MDR) pathogens because of the prevalence of antibiotic use and critical illness in this population. No recommendations have been established for utilization of organs from these OA donors, because data are limited. Herein, we report a case of a 21‐year‐old donor who had sustained a gunshot wound to his abdomen, resulting in a damage‐control laparotomy and abdominal packing. The donor subsequently suffered brain death, and the family consented to organ donation. A multiorgan procurement was performed with respective transplantation of the procured organs (heart, liver, and both kidneys) into 4 separate recipients. Peritoneal swab cultures performed at the time of organ recovery grew out MDR Pseudomonas aeruginosa on the day after procurement, subsequently followed by positive blood and sputum cultures as well. All 4 transplant recipients subsequently developed infections with MDR P. aeruginosa, which appeared to be donor‐derived with similar resistance patterns. Appropriate antibiotic coverage was initiated in all of the patients. Although 2 of the recipients died, mortality did not appear to be clearly associated with the donor‐derived infections. This case illustrates the potential infectious risk associated with organs from donors with an OA, and suggests that aggressive surveillance for occult infections should be pursued.     

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.     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

Anaplasma phagocytophilum presenting with orchitis in a renal transplant recipient

Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, is an emerging tick‐borne disease. It is spread by the black‐legged deer tick Ixodes scapularis that serves as the vector for six human pathogens. HGA is still rarely reported in solid organ transplant recipients. In solid organ transplant recipients, orchitis has been reported secondary to chickenpox, tuberculosis and infections due to Listeria monocytogenes and Nocardia asteroides. Orchitis as a presenting feature of HGA infection has only been reported in animals. We present a unique case of a renal transplant recipient with HGA that presented as orchitis. We also compare the clinical presentation and laboratory findings of our patient with other cases of HGA in transplant recipients. To the best of our knowledge, our patient is one of the first cases of A phagocytophilum mono‐infection causing a classical presentation of orchitis in a transplant patient.     

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.     

Therapeutic apheresis in ABO‐incompatible kidney and liver transplantation: A single‐center experience of 50 patients

ABO antigens play an important role in solid organ transplantation. Desensitization for ABO incompatibility offers patients awaiting transplant a larger donor pool. The aim of this study was to assess outcome of desensitization using the institutional preconditioning protocol in ABO‐incompatible solid organ transplants. A retrospective analysis of ABO‐incompatible solid organ transplants between October 2015 and June 2018, at a tertiary healthcare center was performed. The preconditioning regimen consisted of immunosuppression and therapeutic apheresis (TA). Pre‐ and post‐TA titers were performed, until a target titer of 8 or below was achieved, at which transplant was performed. Follow‐up data till 1 year was analyzed. A total of 50 ABO‐incompatible solid organ transplantations, including 14 liver transplants and 36 renal transplants were analyzed. The median baseline anti‐A and anti‐B titers were 192 and 256, respectively. A total of 150 therapeutic plasma exchange (TPE) procedures were performed for renal transplant recipients; 19 TPE and eight immunoadsorption procedures (five preoperative and three intraoperative) were performed for liver transplant recipients. Five (10%) patients experienced minor adverse events. Biopsy revealed antibody‐mediated rejection was observed in three cases in the immediate posttransplant phase and in three (6.67%) cases over 1 year. There was one death due to transplant‐associated thrombotic microangiopathy. Graft survival for renal transplant was 100% and death‐censored graft survival for liver transplant was 100%. Despite difficulties, ABO‐incompatible transplants can be performed without antibody‐mediated rejection with the use of an appropriate protocol.     

Early listeriosis after liver transplantation: Report of two cases

Listeria monocytogenes is a rare cause of potentially lethal infection and sepsis in transplant recipients. Listeriosis is usually described after kidney or bone marrow transplant, and has been less frequently reported after liver transplantation. Here, the authors present two cases of severe Listeria infection occurring within 4 months after complicated liver transplantation in patients still recovering on the ward. The patients were successfully treated by intravenous ampicillin. These cases should remind transplant physicians that listeriosis may develop in liver transplant recipients, that food safety advice should be provided, and that intravenous ampicillin might be an effective treatment for systemic listeriosis in solid organ recipients. It is likely that trimethoprim‐sulfamethoxazole prophylaxis might help prevent early listeriosis after solid organ transplantation.     

Very early‐onset of Cryptococcus neoformans disease following liver transplantation: Report of two cases and a review of the literature

Cryptococcosis is the third most common invasive fungal infection following solid organ transplantation, and mortality is high. Most cases occur late and are due to reactivation of latent infection; however, very early reactivation and donor‐derived transmission can occur. Routine screening pre‐transplant and antifungal prophylaxis for cryptococcosis post‐transplant in solid organ transplantation are not standard practice. We present two cases of very early‐onset Cryptococcus neoformans disease following liver transplantation to highlight the need to consider individualized pre‐transplant screening and be aware that reactivation of Cryptococcosis neoformans can occur in the immediate post‐transplant period.     

Tuberculous hepatitis in renal transplant recipients following alemtuzumab induction therapy

Mycobacterium tuberculosis infection is one of many opportunistic infections in renal transplant recipients, arising either from reactivation of latent infection or de novo infection, occasionally donor derived. M. tuberculosis hepatitis has never been reported in patients who have received alemtuzumab as part of their renal transplant management. We describe 2 patients who underwent deceased‐donor renal transplantation following alemtuzumab induction therapy and presented with a febrile syndrome, subsequently diagnosed as tuberculous hepatitis, one with disseminated disease. Both responded well to treatment without significant side effects, resulting in excellent graft function. The importance of chemoprophylaxis should be emphasized to minimize the risk of developing active tuberculosis in patients with latent tuberculosis infection undergoing solid organ transplantation.     

High clinical suspicion of donor‐derived disease leads to timely recognition and early intervention to treat solid organ transplant‐transmitted lymphocytic choriomeningitis virus

Despite careful donor screening, unexpected donor‐derived infections continue to occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus (LCMV) is one such transplant‐transmitted infection that in previous reports has resulted in a high mortality among the affected OTRs. We report a LCMV case cluster that occurred 3 weeks post‐transplant in three OTRs who received allografts from a common organ donor in March 2013. Following confirmation of LCMV infection at Centers for Disease Control and Prevention, immunosuppression was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were initiated in OTRs. The liver recipient died, but right kidney recipients survived without significant sequelae and left kidney recipient survived acute LCMV infection with residual mental status deficit. Our series highlights how early recognition led to prompt therapeutic intervention, which may have contributed to more favorable outcome in the kidney transplant recipients.     

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.     

Intrarenal abscess caused by community‐associated methicillin‐resistant Staphylococcus aureus in a transplanted kidney

Emergence of multidrug‐resistant bacteria is important in solid organ transplant recipients, because it can jeopardize patient and graft survival. Methicillin‐resistant Staphylococcus aureus (MRSA) infections are not rare in kidney transplant recipients. On the other hand, infections related to community‐associated MRSA (CA‐MRSA) strains are seldom reported in the literature. Herein, we report the first patient, to our knowledge, with CA‐MRSA renal graft abscess who was successfully treated with drainage and parenteral antibiotics.     

Fatal Fusarium infection manifesting as osteomyelitis following previous treatment with amphotericin B in a multi‐visceral transplant: Case report and review of Fusarium infections in solid organ transplantation

Invasive fusariosis in solid organ transplant is uncommon and usually presents as localized infection with favorable outcomes compared to hematologic malignancies or bone marrow transplants. We report the first case of Fusarium osteomyelitis in a patient following multi‐visceral transplant and review Fusarium in organ transplant recipients and Fusarium bone and joint infections. Our case underscores the importance of early recognition and multidisciplinary approach to treatment and highlights potential failure to eradicate with amphotericin B monotherapy.     

Tick‐borne illness after transplantation: Case and review

Tick‐borne infections in solid organ transplant recipients are an infrequent and difficult diagnostic challenge owing to multiple routes of acquisition and unusual presentations. A 67‐year‐old male recipient of a combined liver and kidney transplant presented with recurrent fevers following surgery. Standard microbiologic workup was non‐diagnostic. Shortness of breath, confusion, lethargy, and hypotension developed along with progressive anemia, requiring multiple blood transfusions. Workup suggested hemolysis and review of the peripheral smear was diagnostic for Babesia microti infection. Tick transmission, transmission via blood products, and/or the transplanted organ were all considered. More extensive questioning revealed a history of intermittent fevers for several months before transplantation. Testing of pre‐transplant blood was positive for B. microti antibodies, suggesting infection prior to transplantation. The delayed diagnosis of babesiosis in this patient highlights the need for a detailed exposure history prior to transplantation, as well as considering the potential for atypical presentations of tick‐borne infections in immune suppressed solid organ recipients. Furthermore, this case illustrates the importance of early Infectious Disease consultation to meet the challenges exhibited by febrile transplant patients. Infectious Diseases physicians are trained to consider, diagnose, and treat tick‐borne infections, contributing to improved clinical outcome.     

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients

D. Neofytos, J.A. Fishman, D. Horn, E. Anaissie, C.‐H. Chang, A. Olyaei, M. Pfaller, W.J. Steinbach, K.M. Webster, K.A. Marr. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.
Transpl Infect Dis 2010: 12: 220–229. All rights reserved Abstract: Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received ≥2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12‐week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non‐lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.     

Donor-derived organ transplant transmission of coccidioidomycosis

Coccidioidomycosis in solid organ transplant recipients most often occurs as a result of primary infection or reactivation of latent infection. Herein, we report a series of cases of transplant-related transmission of coccidioidomycosis from a single donor from a non-endemic region whose organs were transplanted to 5 different recipients. In all, 3 of the 5 recipients developed evidence of Coccidioides infection, 2 of whom had disseminated disease. The degree of T-cell immunosuppression and timing of antifungal therapy initiation likely contributed to development of disease and disease severity in these recipients. This case series highlights the importance of having a high index of suspicion for Coccidioides infection in solid organ transplant recipients, even if the donor does not have known exposure, given the difficulties of obtaining a detailed and accurate travel history from next-of-kin.