Risk Classification for Respiratory Viral Infections in Adult Solid Organ Transplantation Recipients

IntroductionMolecular testing such as nasopharyngeal viral polymerase chain reaction (PCR) (NVP) is available now in most hospitals and widely used to identify respiratory viral infections (RVIs) in solid organ transplantation (SOT) recipients.Materials and MethodsA retrospective multicenter study at 8 hospitals from March 1, 2016, to April 30, 2019. We included all adult SOT recipients who were admitted to the hospitals and had their first NVP post transplantation.ResultsA total of 102 adult SOT recipients were enrolled. NVP test was positive in 33 (32.4%) SOT recipients and negative in 69 (67.6%). Median age was more than 60 years old with female predominance in both groups. The majority of patients who had positive NVP were hospitalized either in fall or winter seasons (91%). RVI symptoms were documented in about 73% of the positive NVP group. Rhinovirus was the most common identified virus (48.4%). On logistic regression analysis, clinical presentation in fall or winter seasons, presenting with upper respiratory infection (URI) symptoms and taking prednisone ≥10 mg/d were significantly associated with positive NVP. This model classified patients into 3 categories of risk for RVIs—low (none of the variables), 0%; intermediate (1 variable), 6.5%; and high (≥2 variables), 55.4% with P < .001 for all predictors.ConclusionSOT recipients who are taking prednisone (≥10 mg) and have URI symptoms in fall or winter seasons are more likely to have RVIs     

Risk Factors for Hepatotoxicity in Solid Organ Transplants Recipients Being Treated for Tuberculosis

BackgroundTuberculosis (TB) is associated with high morbidity and mortality in solid organ transplant (SOT) recipients. Also, SOT patients have a 20- to 74-fold increase in the chance of developing TB compared to the general population. Here we evaluated the incidence of hepatotoxicity in SOT recipients on treatment for TB and determined risk factors for liver toxicity in these patients.Patients and MethodsRetrospective cohort conducted in a reference hospital for SOT in Southern Brazil. All SOT recipients who underwent TB treatment during the years 2000–2012 were considered for the study.ResultsA total of 69 patients were included in the study and 23 had liver toxicity (incidence 33.3%). Independent risk factors for hepatotoxicity were rifampin use at doses of ≥600 mg daily (P = .016; OR 2.47; 95% CI, 1.18–5.15) and lung transplantation (P = .017; OR 2.05; 95% CI, 1.14–3.70). Kidney transplantation appeared as a protective factor (P = .036; OR 0.50; 95% CI, 0.26–0.96). Mortality was higher in the patients who had hepatotoxicity (43.5%), compared with those who did not (19.6%).ConclusionIn this study, the use of rifampin at doses of 600 mg daily or higher was found to be an independent risk factor for liver toxicity in SOT recipients. The importance of additional risk factors for hepatotoxicity, such as lung transplantation as well as the protective role of kidney transplantation, should be better investigated in SOT recipients being treated for TB.     

Risk of Thyroid Cancer Among Solid Organ Transplant Recipients

Solid organ transplant recipients have an elevated incidence of thyroid cancer. We evaluated a wide range of potential risk factors in a cohort of 229 300 U.S. solid organ transplant recipients linked with 15 stage/regional cancer registries (1987–2012). Incidence rate ratios (IRRs) were adjusted for age, sex, race/ethnicity, transplanted organ, year of transplantation, and time since transplantation. Hazard ratios (HRs) for death and/or graft failure were adjusted for age, sex, race/ethnicity, transplanted organ, and year of transplantation. After transplantation, 356 thyroid cancers were diagnosed. Thyroid cancer incidence was 2.50‐fold higher in transplant recipients than the general population (95% confidence interval [CI] 2.25–2.77). Among recipients of different organs, kidney recipients had the highest incidence of thyroid cancer (IRR = 1.26, 95% CI 1.03–1.53). Elevated thyroid cancer incidence was associated with cholestatic liver disease/cirrhosis as an indication for liver transplantation (IRR = 1.69, 95% CI 1.09–2.63), hypertensive nephrosclerosis as an indication for kidney transplantation (IRR = 1.41, 95% CI 1.03–1.94), and longer prior dialysis among kidney recipients (5+ vs. <1 year, IRR = 1.92, 95% CI 1.32–2.80; p‐trend <0.01). Posttransplantation diagnosis of thyroid cancer was associated with modestly increased risk of death (HR = 1.33, 95% CI 1.02–1.73). Overall, our results suggest that end‐stage organ disease and longer duration of dialysis may contribute to higher thyroid cancer incidence in transplant recipients.     

Uptake of Cancer Screening Tests Among Recipients of Solid Organ Transplantation

Population‐based cancer screening recommendations are also suggested for solid organ transplant recipients (SOTR); however, recommendation adherence is unknown. In a population‐based cohort of SOTR in Ontario between 1997 and 2010, we determined the uptake of breast, cervical, and colorectal cancer screening tests and identified factors associated with up‐to‐date screening using recurrent event analysis. We identified 4436 SOTR eligible for colorectal, 2252 for cervical, and 1551 for breast cancer screening. Of those, 3437 (77.5%), 1572 (69.8%), and 1417 (91.4%), respectively, were not up‐to‐date for cancer screening tests during the observation period. However, these rates are likely an overestimate due to the inability to differentiate between tests done for screening or for diagnosis. SOTR with fewer comorbidities had higher rates of becoming screen up‐to‐date. Assessment by a primary care provider (PCP) was associated with becoming up‐to‐date with cancer screening (breast relative risk [RR] = 1.40, 95% confidence interval [CI]: 1.12–1.76, cervical RR = 1.29, 95% CI: 1.06–1.57, colorectal RR = 1.30, 95% CI: 1.15–1.48). Similar results were observed for continuity of care by transplant specialist at a transplant center. In conclusion, cancer screening for most SOTR does not adhere to standard recommendations. Involvement of PCPs in posttransplant care and continuity of care at a transplant center may improve the uptake of screening.     

Antibiotic Stewardship and Inpatient Clostridioides difficile Testing in Solid Organ Transplant Recipients: The Need for Multilevel Checks and Balances

BackgroundDiarrhea among recipients of solid organ transplants is a commonly encountered problem and is often multifactorial in etiology. Owing to the combination of perioperative antibiotic administration and the immunosuppressed status of transplant recipients, a high degree of suspicion for Clostridioides difficile (C. difficile) colitis is prudent. The purpose of this study is to demonstrate the association of an institutional integrated stewardship program with C. difficile testing practices after abdominal solid organ transplantation.MethodsStarting in July 2017, a diagnostic stewardship was enacted in our institution requiring the ordering provider to answer a series of questions within the electronic medical record before ordering a C. difficile toxin test. The charts were reviewed for all solid organ transplant recipients on whom a test was ordered between January 2016 and September 2019.ResultsOrders for C. difficile toxin per quarter significantly decreased in the postintervention era (18 vs 8.5, P = .038). Median cost of inpatient treatment and days of therapy per thousand patient days was significantly lower in the postintervention era (median cost, $2,944.55 vs $416.92; P = .01) (days of therapy per thousand patient days, 521.9 vs 300.5; P < .01). Quarterly rates of negative tests were similar between the pre- and postintervention eras (65% vs 73%, P = .38).ConclusionsAlthough no orders were blocked based on the responses, this multilevel intervention was associated with a 47% decrease in C. difficile testing without effecting the rate of negative testing. These results suggest that we have achieved significant cost savings, in testing and isolation, without sacrificing critical aspects of clinical care.     

Remdesivir in Solid Organ Recipients for COVID-19 Pneumonia

Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters.     

Chikungunya Infection in Solid Organ Transplant Recipients

Background

Chikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients.

Management of Epstein–Barr Virus-induced Post-transplant Lymphoproliferative Disease in Recipients of Solid Organ Transplantation

The optimal management of Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative diseases (PTLD) remains controversial. While withdrawal or reduction of immunosuppression is widely accepted as the strategy for the treatment of EBV/PTLD, the role of additional therapeutic interventions remains less clear. Newer strategies, including anti-B-cell monoclonal antibodies and adoptive immunotherapy offer the promise of impaired efficacy and outcome against EBV disease, but lack data demonstrating how and when to use these approaches. The current review provides an overview of potential strategies and presents guidelines for the management of EBV/PTLD in solid-organ transplant recipients.     

Solid Organ Transplantation in AL Amyloidosis

Vital organ failure remains common in AL amyloidosis. Solid organ transplantation is contentious because of the multisystem nature of this disease and risk of recurrence in the graft. We report outcome among all AL patients evaluated at the UK National Amyloidosis Centre who received solid organ transplants between 1984 and 2009. Renal, cardiac and liver transplants were performed in 22, 14 and 9 patients respectively, representing <2% of all AL patients assessed during the period. One and 5‐year patient survival was 95% and 67% among kidney recipients, 86% and 45% among heart recipients and 33% and 22% among liver recipients. No renal graft failed due to recurrent amyloid during median (range) follow up of 4.8 (0.2–13.3) years. Median patient survival was 9.7 years among 8/14 cardiac transplant recipients who underwent subsequent stem cell transplantation (SCT) and 3.4 years in six patients who did not undergo SCT (p = 0.01). Amyloid was widespread in all liver transplant recipients. Solid organ transplantation has rarely been performed in AL amyloidosis, but these findings demonstrate feasibility and support a role in selected patients.     

Early Bacteremia After Solid Organ Transplantation

Objective

Bloodstream infections (BSI) are a major cause of morbidity and mortality after solid organ transplantation. Our aim was to analyze early BSI after solid organ transplantation.

Materials and Methods

A prospective cohort study included patients undergoing a kidney, simultaneous kidney-pancreas (SPK), or orthotopic liver transplantation (OLT) from 2003-2007. We prospectively collected demographic variables, underlying chronic diseases, transplantation procedures, and posttransplant complications. Recorded cases of BSI were defined as significant according to CDC criteria. Early BSIs were considered to be those appearing within 30 days posttransplantation.

Results

During the study period, we performed 902 transplantations: 474 renal, 340 liver, and 88 pancreas. Seventy episodes of early BSI were diagnosed in 67 patients (7.4%). The incidences of BSI according to the type of transplantation were: 4.8% in renal, 4.5% in SPK, and 12% in OLT (P < .001). Sixty-three percent of the bacteria isolated were gram-negative, the most frequent being Escherichia coli, of which 18 (54%) were extended-spectrum beta-lactamase-producing (ESBL), and Pseudomonas aeruginosa, of which 18 (31%) were multidrug-resistant. The most frequent gram-positive bacteria were coagulase-negative staphylococci (20%). The urinary tract was a frequent source of BSI (27%), followed by a catheter (18%). Two patients (3%) died, both liver recipients, but neither death was related to the BSI.

Conclusions

In our setting, the incidence of early BSI among solid organ transplant recipients was high, especially liver recipients, but with low associated mortality. The most frequent sources of infection were urinary tract and catheter. Gram-negative BSI showed a high rate of multidrug resistance.     

Risk of Colorectal Cancer After Solid Organ Transplantation in the United States

Solid organ transplant recipients have increased colorectal cancer (CRC) risk. We assessed CRC risk among transplant recipients and identified factors contributing to this association. The US transplant registry was linked to 15 population‐based cancer registries (1987–2010). We compared CRC risk in recipients to the general population by using standardized incidence ratios (SIRs) and identified CRC risk factors by using Poisson regression. Based on 790 cases of CRC among 224 098 transplant recipients, the recipients had elevated CRC risk (SIR 1.12, 95% confidence interval [CI] 1.04 to 1.20). The increase was driven by an excess of proximal colon cancer (SIR 1.69, 95% CI 1.53 to 1.87), while distal colon cancer was not increased (SIR 0.93, 95% CI 0.80 to 1.07), and rectal cancer was reduced (SIR 0.64, 95% CI 0.54 to 0.76). In multivariate analyses, CRC was increased markedly in lung recipients with cystic fibrosis (incidence rate ratio [IRR] 12.3, 95% CI 6.94 to 21.9, vs. kidney recipients). Liver recipients with primary sclerosing cholangitis and inflammatory bowel disease also had elevated CRC risk (IRR 5.32, 95% CI 3.73 to 7.58). Maintenance therapy with cyclosporine and azathioprine was associated with proximal colon cancer (IRR 1.53, 95% CI 1.05 to 2.23). Incidence was not elevated in a subgroup of kidney recipients treated with tacrolimus and mycophenolate mofetil, pointing to the relevance of the identified risk factors. Transplant recipients have increased proximal colon cancer risk, likely related to underlying medical conditions (cystic fibrosis and primary sclerosing cholangitis) and specific immunosuppressive regimens.