Ignacio A. Echenique

Diagnostic Yields in Solid Organ Transplant Recipients Admitted With Diarrhea

BACKGROUND Although diarrhea is a frequent complaint among solid organ transplant recipients, the contribution of infectious etiologies remains incompletely defined. We sought to define the etiologies of diarrhea and the yields of testing at our institution. METHODS We performed a retrospective analysis over an 18-month period of hospitalized solid organ transplant recipients. We stratified diarrhea by community onset vs hospital onset of diarrhea. RESULTS We identified 422 admissions (representing 314 unique patients) with community-onset diarrhea, and 112 admissions (representing 102 unique patients) with hospital-onset diarrhea. The majority of community- and hospital-onset diarrheal episodes had no identified etiology (60.9% and 75.9%, respectively; P = .03), yet were also self-limited (91% and 91%, respectively; P = .894). Thereafter, the most frequently encountered infectious etiologies were Clostridium difficile infection (13.3% and 11.8%, respectively), norovirus enteritis (8.2% and 3%), cytomegalovirus disease or colitis (6.3% and 2.7%), and bacterial enterocolitis (0.9% and 0%) (P = .03). In aggregate, these entities represented 93.7% and 90.5% of the identified infectious etiologies, respectively. Protozoan causes were rarely seen. Coinfection, or the simultaneous detection of ≥2 pathogens, occurred in 8 (1.9%) and 2 (1.8%) community- and hospital-onset diarrheal admissions, respectively (P = .99). CONCLUSIONS In solid organ transplant recipients who presented at our institution with diarrhea, approximately one-third had infectious etiologies identified, consisting predominantly of C. difficile, norovirus, cytomegalovirus, and bacterial enterocolitis. Other infectious etiologies were rare.

Considerations for Screening Live Kidney Donors for Endemic Infections: A Viewpoint on the UNOS Policy

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease‐specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at‐risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus

Norovirus is a major cause of self‐limited gastroenteritis worldwide. Prevention and treatment are thwarted by rapid viral evolution, and thus supportive care remains the mainstay of therapy. Chronic infection in immunocompromised hosts is increasingly described. We report a case of norovirus infection lasting 2543 days in a pancreas transplant recipient. Serial fecal specimens were obtained, from which a map of genetic relatedness was derived. The clinical course was complicated by renal failure that progressed to end‐stage renal disease. Minimization of immunosuppression was associated with resolution of the infection. Subsequently, the patient experienced a suspected allograft rejection that did not compromise pancreas function. The patient later underwent living‐related renal transplantation without recurrence of enteritis.

Impact of repeat testing of living kidney donors within 14 days of the transplant procedure: a multicenter retrospective survey

A transmission of human immunodeficiency virus (HIV) from a live kidney donor prompted recommendations by the New York State Department of Health and the US Centers for Disease Control and Prevention that all live donors undergo additional screening for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) within 7–14 days of the donation procedure. There are concerns that re‐screening will result in delays and cancelled transplants.

HIV and Stem Cell Transplantation

In human immunodeficiency virus (HIV)-infected persons, the incidence of hematologic malignancies, including leukemia and lymphoma, is increased despite the use of successful antiretroviral therapy. Hematopoietic stem cell transplantation (SCT) is emerging as a safe and effective therapy for HIV-infected persons with hematologic malignancies. Management of these patients is complicated by drug–drug interactions involving antiretroviral therapy (ART) that may impact conditioning agent efficacy and metabolism of immunosuppressive medications and potentiate drug toxicities. As such, optimal strategies for ART remain controversial. We discuss recent advances, controversies, and future directions related to SCT in HIV-infected persons, including the investigation of allogeneic SCT as a strategy for HIV cure.

Update on donor-derived infections in liver transplantation

Advances in surgical techniques, immunosuppressive medications, and robust infectious disease prophylaxis have resulted in liver transplantation becoming the treatment of choice for patients with end‐stage liver disease and unresectable hepatocellular carcinoma. Nonetheless, organ transplantation is not without risk. Unexpected donor‐derived disease transmission is a newly recognized risk that complicates approximately 0.2% of all organ transplants. We review the epidemiology of donor‐derived infectious diseases and methods of risk mitigation with a focus on liver transplantation. Liver Transpl 19:575–585, 2013.

Variability in assessing for BK viremia: whole blood is not reliable and plasma is not above reproach – a retrospective analysis

Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy‐proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high‐level BK viruria. All biopsies showed polyoma virus large T‐antigen expression in tubular epithelium using immunohistochemistry. All had viruria preceding or at the time of biopsy (range, 5.2 × 104 to >25 × 106 BKV DNA copies/ml). Twenty (69%) had viremia ranging from 2.5 × 103 to 4.3 × 106 copies/ml at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed positive detection of viremia. A comparative analysis of assays from two centres was performed with spiked samples. BK DNA may not be detected in the blood of some kidney transplant recipients with histologically confirmed PVN. This may reflect limitation of whole blood as opposed to plasma‐based BK DNA assessment.

Invasive fungal infection after heart transplantation: A 7-year, single-center experience

Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution.

A bridge too far

To the Editor We read the recent article by Bert et al. (1) with great interest. Retrospectively they identified liver transplant recipients screened for extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae at their institution. From patient characteristics, a univariate analysis was performed to determine risk factors for ESBL carriage. They concluded “[t]hese high-risk patients should receive [ESBL-Enterobacteriaceae]targeted intraoperative prophylaxis and, when appropriate, empiric postoperative antimicrobial treatment.” We were surprised to see a recommendation of tremendous consequence relegated to a brief remark, and we disagree that the presented findings support empiric, broader peri-operative coverage during liver transplantation. The risk factors identified may not effectively identify patients for ESBL carriage at other centers, given variation in local epidemiology both in the surrounding communities and the center itself (2–4). A multitude of factors impact a patient’s normal flora. Such factors, not included in the current study, may include preand post-transplant lengths of stay, timing of infection, travel history, outpatient care setting, history of spontaneous bacterial peritonitis (SBP), type of SBP prophylaxis, presence and duration of critical illness, history of previous antimicrobial therapy, history and type of any multidrug-resistant organism, and type of peri-operative antibiotic therapy (5). Thus, a univariate assessment of limited factors is insufficient. A more measured approach would have each institution perform their own risk factor analysis and establish prophylaxis thresholds. Another, possibly superior, strategy might be to target prophylaxis based on known colonization with an ESBL. The authors outline their opposition to this approach, including a concern regarding the sensitivity of a pre-operative peri-rectal swab. Nonetheless, they cite a comparative phenotypic analysis where two-step testing approached 100% sensitivity (6). Knowledge of the intervening events including time between swabs, antibiotic exposure, and so on is essential to revealing the natural history of ESBL acquisition. Further, the consequences of these recommendations must be considered. Altering prophylaxis-based risk factors, rather than ESBL colonization status itself, would unnecessarily expose more individuals to broader agents (as per their Table 3, all patients with 1 or more risk factors, or 119 versus the estimated

Cytomegalovirus infection in heart transplantation: A single center experience

Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation.