Meenakshi Rana

Donor-derived Strongyloides stercoralis infection in solid organ transplant recipients in the United States, 2009-2013.

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Preventions experience with seven clusters of donor‐derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor‐derived infection can be averted in recipients.

Transmission of Methicillin-Resistant Staphylococcus aureus via Deceased Donor Liver Transplantation Confirmed by Whole Genome Sequencing

Donor‐derived bacterial infection is a recognized complication of solid organ transplantation (SOT). The present report describes the clinical details and successful outcome in a liver transplant recipient despite transmission of methicillin‐resistant Staphylococcus aureus (MRSA) from a deceased donor with MRSA endocarditis and bacteremia. We further describe whole genome sequencing (WGS) and complete de novo assembly of the donor and recipient MRSA isolate genomes, which confirms that both isolates are genetically 100% identical. We propose that similar application of WGS techniques to future investigations of donor bacterial transmission would strengthen the definition of proven bacterial transmission in SOT, particularly in the presence of highly clonal bacteria such as MRSA. WGS will further improve our understanding of the epidemiology of bacterial transmission in SOT and the risk of adverse patient outcomes when it occurs.

Klebsiella necrotizing soft tissue infections in liver transplant recipients: a case series

Necrotizing soft tissue infections (NSTI) are rare but carry high mortality rates. NSTI with Klebsiella species have been previously described as associated with Klebsiella liver abscesses and endophthalmitis. Here, we describe 6 cases of NSTI in liver transplant recipients associated with Klebsiella pneumoniae, 4 of which were K. pneumoniae carbapenemase (KPC)‐producing K. pneumoniae (CRKP). Increased awareness of this emerging pathogen and its association with necrotizing skin and soft tissue infection is critical, as early recognition and debridement may improve survival. Antimicrobial treatment of CRKP infections remains an ongoing challenge and implementation of enhanced infection control measures is essential.

Belatacept Conversion in an HIV‐Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function

We report an HIV‐positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow‐up. To our knowledge, this is the first report of belatacept use in a patient with HIV.

Multidrug-Resistant Bacteria in Organ Transplantation: An Emerging Threat with Limited Therapeutic Options

Multidrug-resistant organisms (MDROs) are an emerging threat in solid organ transplantation (SOT). The changing epidemiology of these MDROs is reviewed along with the growing evidence regarding risk factors and outcomes associated with both colonization and infection in SOT. The management of these infections is complicated by the lack of antimicrobial agents available to treat these infections, and only a handful of new agents, especially for the treatment of MDR GNR infections, are being evaluated in clinical trials. Due to the increased prevalence of MDROs and limited treatment options, as well as organ shortages, transplant candidacy and use of organs from donors with evidence of MDRO colonization and/or infection remain controversial. Increasing collaboration between transplant programs, individual practitioners, infection control programs, and researchers in antimicrobial development will be needed to face this challenge.

The Epidemiology and Clinical Features of Clostridium difficile Infection in Liver Transplant Recipients.

Background Clostridium difficile infection (CDI) is common after liver transplantation (LT); however, few studies have examined the risk factors, clinical manifestations, and outcomes of CDI in this population. Methods A retrospective study of adults who underwent LT between January 1, 2011, and April 4, 2013, at The Mount Sinai Hospital was conducted. Potential risk factors were evaluated via univariate and multivariable analysis to determine predictors of CDI in this population. The clinical manifestations of CDI and patient outcomes were also reviewed. Results Clostridium difficile infection occurred in 27 (14%) of 192 patients after LT. In multivariable analysis, CDI was associated with having a model for end-stage liver disease score of 20 or greater (hazards ratio, 2.90; 95% confidence interval, 1.29-6.52; P = 0.010), and receiving a LT from a living donor (hazards ratio, 3.77; 95% confidence interval, 1.47-9.67; P = 0.006). Forty-one percent of CDI cases occurred within 1 week of LT. Seven percent of patients with CDI had a serum white blood cell count greater than 12 000 cells per &mgr;L, and 26% had a temperature greater than 38.0°C. After treatment 6 (22%) patients developed CDI relapse, and all were successfully treated. No patients died of CDI after a mean follow-up time of 1.8 years; however, overall survival was significantly lower among those with CDI (78% vs 92%; P = 0.033). Conclusions Clostridium difficile infection after LT was associated with higher model for end-stage liver disease scores and receiving a LT from a living donor. Clostridium difficile infection often occurred soon after LT and was infrequently associated with leukocytosis or fever. Clostridium difficile infection in LT recipients was associated with lower overall survival.

Screening recipients of increased risk donor organs: A multicenter retrospective study

Organ Procurement & Transplantation Network policy requires post‐transplant screening of recipients of organs from donors at increased risk for transmission of HIV, hepatitis B virus, and hepatitis C virus. Available data suggest that follow‐up testing of recipients is not routinely conducted. Data on increased risk donors and recipients of their organs from 2008 to 2012 were retrospectively collected from 6 transplant centers after IRB approval. Descriptive statistics were performed. About 363 (60%) recipients were screened for transmission of HIV, HBV, and/or HCV at some time point; 257 (70.8%) within 90 days of transplant. The type of test used to screen for infection was variable with many recipients (25%‐43%) screened with serology alone. Our results reveal that post‐transplant screening for HIV, HBV, and HCV in recipients of increased risk donor organs did not universally occur and testing methods were variable.

A case of Strongyloides hyperinfection syndrome in the setting of persistent eosinophilia but negative serology

Strongyloides stercoralis is a unique intestinal nematode with the ability to replicate and complete its life cycle without leaving the host. We report a fatal case of Strongyloides hyperinfection syndrome in a patient who had persistent eosinophilia for several years but negative Strongyloides serology. Our case suggests that ELISA serologies cannot solely be relied upon to diagnose Strongyloides stercoralis infection; history and clinical judgment remain crucial to this diagnosis.

Higher Rates of Rejection in HIV-infected Kidney Transplant Recipients on Ritonavir-Boosted Protease Inhibitors-Three-Year Follow Up

Background One-year rejection rates in HIV-infected kidney transplant recipients range from 15-40%, compared to overall rejection rates of 10% in HIV-negative patients. Protocols for immunosuppression and highly active antiretroviral therapy (HAART) vary substantially and there is potential for significant drug-drug interactions, specifically between ritonavir-boosted protease inhibitors (rtv+ PI) and calcineurin inhibitors. Methods This is an IRB-approved, single center, retrospective study of adult HIV-infected patients who underwent a kidney transplantation between 5/2009 to 12/2014 with a three-year follow up for each patient. Results Forty-two patients were identified with a median age of 52 (47, 57) years. Of these, 81% were male and 50% were African American, 29% were Hispanic, and 17% were Caucasian. The most common cause of renal failure was hypertensive nephrosclerosis (50%) followed by HIV-associated nephropathy (14%), and the median duration of pre-transplant dialysis was 5.8 (2.8, 8.7) years. All patients were induced with IL-2 receptor antagonist (IL-2 RA): 83% with basiliximab and 17% with daclizumab induction. Calcineurin inhibitor therapy included tacrolimus (76%), cyclosporine (17%), or transitions between these two (7%). 40% of patients received a rtv+ PI-based HAART regimen. At 30 days, patient and graft survival were 100%. Patient and graft survival were consistent at 93% and 90%, respectively, at years one, two, and three. Overall treated biopsy-proven rejection rates at one, two, and three years were 38%, 38%, and 41%, respectively, and 92% of these episodes were acute rejection. At one, two, and three years, rejection rates were significantly higher for recipients on rtv+PI compared to those on other HAART regimens as 59% vs 24% (p=0.029), 59% vs 24% (p=0.029), and 68% vs 24% (p=0.01), respectively. Conclusion HIV-infected kidney transplant recipients maintain excellent outcomes despite higher rates of acute rejection relative to HIV negative recipients. Given the significantly higher rates of rejection at one, two, and three years in the rtv + PI group, alternative HAART regimens should be considered prior to transplant when possible.

Successful heart transplantation in patients with active Staphylococcus bloodstream infection and suspected mechanical circulatory support device infection

An active bloodstream infection (BSI) is typically considered a contraindication to heart transplantation (HT). However, in some patients with Staphylococcus bacteremia and mechanical circulatory support device infection, positive blood cultures may persist until removal of the infected device, and eradicating the infection prior to HT may not be possible. We report the outcomes of six patients with active Staphylococcus BSI at the time of HT.