Frequency and risks associated with Clostridium difficile-associated diarrhea after pediatric solid organ transplantation: a single-center retrospective review.

BACKGROUND: Morbidity and mortality related to Clostridium difficile infection (CDI) has increased, but epidemiology and risk factors within pediatric solid organ transplant (SOT) recipients are uncertain. METHODS: A retrospective cohort study of SOT recipients age ≤18 years at transplantation from 2010 to 2013 was performed. Patients with CDI were compared with matched CDI-negative controls with diarrhea. RESULTS: Of 202 patients, the majority were male (58%) and Caucasian (77%). Kidney (42%) was the most common organ transplanted, followed by liver (38%), heart (17%), and multivisceral/intestine (3%). Age ranged from 3 weeks to 18 years (median 4.7 years, mean 6.6; interquartile range [IQR] 1.5-11.2). In 104 SOT recipients, at least 1 unformed stool was tested; 25 patients were positive for CDI. Most testing occurred by 60 days post transplant (mean 164, median 57, IQR 14-227). First negative tests occurred concurrently (mean 153, median 54, IQR 13-214) to the 25 patients with CDI (mean 199, median 65, IQR 32-238). In univariable analyses, age, gender, ethnicity, obesity, and calcineurin inhibitor choice were not associated with CDI. Liver recipients were more likely to have CDI (18.4% liver, 4.7% kidney, 8.8% heart, P < 0.01). Twenty CDI patients were matched to 35 controls. In multivariable analyses, neither recent hospitalization nor antibiotic duration or intensity was associated with CDI. Acid-blockade appeared protective (risk ratio 0.13, 95% confidence interval 0.02-0.78). CONCLUSIONS: CDI occurs in 12% of pediatric SOT recipients, but 24% of those tested with diarrhea were positive. In patients with diarrhea, prior hospitalization and antibiotic duration or intensity were not associated with CDI.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Current prevention strategies against cytomegalovirus in the studies in pediatric liver transplantation (SPLIT) centers.

Cytomegalovirus (CMV) continues to be a significant posttransplant infectious complication after pediatric liver transplant (PLT). The optimal prevention strategy is not currently known. To assess current CMV prevention practices, a web-based survey was conducted within the North American Studies in Pediatric Liver Transplantation (SPLIT) network. Twenty-nine of the 31 centers (94%) surveyed responded. Only seven centers reported evidence-based development of protocols. For most at-risk (donor or recipient CMV seropositive) PLT recipients, a prophylactic strategy predominates current practice. For high-risk (D+/R-), only three centers used nonprophylaxis-based protocols: one preemptive and two sequential/hybrid. Duration of prophylaxis ranged from 84 to 730 days with 14 centers using around 100 days and nine centers using around 200 days. Initial therapy with ganciclovir followed by valganciclovir was the most common strategy. For lower-risk recipients (CMV D-/R-), more centers (10/29) employed a preemptive strategy while the remainder described prophylaxis (15) and sequential/hybrid (3) strategies. Prophylaxis predominates current CMV prevention strategies for at-risk recipients within SPLIT. The variation in duration of therapy provides the opportunity to perform comparative effectiveness studies within SPLIT.

Influenza vaccination in the organ transplant recipient: review and summary recommendations.

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker.

Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity. We studied 31 kidney transplant recipients treated with either antithymocyte globulin (ATG) or an IL-2 receptor blocker. We tested pre- and posttransplant peripheral blood cells by flow cytometry to characterize T-cell populations and by IFN-γ ELISPOT assays to assess the level of cellular alloreactivity. CD8(+) T cells were more resistant to depletion by ATG than CD4(+) T cells. Posttransplantation, frequencies of donor-reactive T cells were markedly decreased in the ATG-treated group but not in the IL-2 receptor blocker group, whereas the frequencies of third-party alloreactivity remained nearly equivalent. In conclusion, when ATG is used, marked and prolonged donor hyporesponsiveness with minimal effects on nondonor responses is observed. In contrast, induction with the IL-2 receptor blocker is less effective at diminishing donor T-cell reactivity.

Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group.

The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.

Clostridium difficile colitis in children following lung transplantation.

Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.

Long-term impact of respiratory viral infection after pediatric lung transplantation.

To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank-sum tests and Fisher's exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty-five subjects were followed for a mean of 674 days (range 14-1790). Twenty-eight (51%) developed 51 RVI at a median of 144 days post-transplant (mean 246; range 1-1276); 41% of infections were diagnosed within 90 days. Twenty-five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1-5.3 and 17.0; 3.0-96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.

Respiratory viral infections within one year after pediatric lung transplant.

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post-transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank-sum and chi(2) tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12-month survival (hazard ratio 2.6, 95% confidence interval 1.6-4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non-CF diagnosis. RVI is associated with decreased 1-year survival.

American Society of Transplantation executive summary on pediatric lung transplantation.

Lung transplantation in children poses distinctly different challenges from those seen in the adult population. This consensus statement reviews the experience in the field of pediatric lung transplantation and highlights areas that deserve further investigation.