Denise Schain

Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients.

ABSTRACT We review the experience at our institution with galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16), there were five cases of proven or probable IPA. All five patients had BAL GM of ≥2.1 and survived following antifungal therapy. The sensitivity, specificity, and positive and negative predictive values for BAL GM testing at a cutoff of ≥1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The sensitivity of BAL GM testing was better than that of conventional tests such as serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed IPA several days to 4 weeks before other methods for three patients. Twelve patients had BAL GM of ≥0.5 but no evidence of IPA. Among these, lung transplant recipients accounted for 41.7% (5/12) of the false-positive results, reflecting frequent colonization of airways in this population. Excluding lung transplants, the specificity and positive predictive value for other solid-organ transplants increased to 92.9% and 62.5%, respectively (cutoff, ≥1.0). In conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the institution of antifungal therapy among non-lung solid-organ transplant recipients and helped to rule out IPA.

Transmission of Cryptococcus neoformans by Organ Transplantation

BACKGROUND This article describes transmission of Cryptococcus neoformans by solid organ transplantation. METHODS We reviewed medical records and performed molecular genotyping of isolates to determine potential for donor transmission of Cryptococcus. RESULTS Cryptococcosis was diagnosed in 3 recipients of organs from a common donor with an undifferentiated neurologic condition at the time of death. Cryptococcal meningoencephalitis was later diagnosed in the donor at autopsy. The liver and 1 kidney recipient developed cryptococcemia and pneumonia and the other kidney recipient developed cryptococcemia and meningitis; 2 patients recovered with prolonged antifungal therapy. We tested 4 recipient isolates with multilocus sequence typing and found they had identical alleles. CONCLUSIONS Our investigation documents the transmission of Cryptococcus neoformans by organ transplantation. Evaluation for cryptococcosis in donors with unexplained neurologic symptoms should be strongly considered.

Case of emphysematous pyelonephritis in a renal allograft

Abstract:  Emphysematous pyelonephritis is a rare, but serious complication after renal transplantation. This is a case report of a 49‐yr‐old female who had a renal transplant for diabetic nephropathy. She presented to ER with about 1 wk history of right lower abdominal pain and fever 15 months after the transplant. She had gross hematuria and mental status changes just prior to presentation. A computed tomography (CT) scan of the abdomen showed extensive retroperitoneal and extraperitoneal air dissecting from the transplanted kidney in the right lower quadrant to the level of the mediastinum. There was air in the urinary bladder. These findings were highly suggestive of extensive emphysematous pyelonephritis. The patient was taken to the operating room emergently and underwent a transplant nephrectomy. Blood culture and urine culture were subsequently positive for Salmonella (serogroup O 6, 8 or C2). Initial blood culture also yielded Enterobacter cloacae. The patient was treated with imipenem, cefepime, flagyl, and diflucan empirically: this was later changed to complete a 6‐wk course of ciprofloxacin upon discharge. Her hospital course was complicated by a urinary leak; she was discharged to home on day 21. This is the 12th reported case of emphysematous pyelonephritis occurred in a renal transplant recipient.

The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States

Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.

Effect of prophylaxis on fungal infection and costs for high‐risk liver transplant recipients

We sought to determine whether the prophylactic use of amphotericin B products (conventional amphotericin B and liposomal amphotericin B) reduces the incidence of fungal infections in high‐risk liver transplant recipients, and if so, whether this lowers the cost of care. The study sample comprised 232 adult orthotopic liver transplants performed from 1994 to 2005 at a single center for patients classified as being at high risk for fungal infections. High‐risk patients who received transplants with a prophylaxis regimen of amphotericin B (n = 58 transplants) were compared with high‐risk patients who received no prophylaxis (n = 174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those who received amphotericin B and 28 transplants (16.09%) in those without prophylaxis (P = 0.0432). Regression models were used to analyze fungal infection and costs for the 232 high‐risk transplants. Failure to offer prophylaxis conferred a 4‐fold greater risk of fungal infection (P = 0.046) compared with those who received amphotericin B. A fungal infection in a high‐risk recipient increased mean costs by 46.48%. The indirect effect of prophylaxis (operating through infection reduction) is estimated to reduce overall costs in high‐risk patients by 8.73%. Liver Transpl 13: 1743–1750, 2007.

Ureteral stent placement and BK viremia in kidney transplant recipients

BK virus (BKV) infection is an important cause of kidney transplant dysfunction. A possible association of double‐J ureteral stent placement and BK viremia has been suggested in previous studies; however, risk factors for BK are incompletely understood. We aimed to determine if stent placement is an independent risk factor for BK viremia.

Strongyloides hyperinfection syndrome following simultaneous heart and kidney transplantation

We report a case of Strongyloides hyperinfection syndrome (SHS) causing death in a patient approximately 1 month following simultaneous heart and kidney transplantation (HKTx). The patient was a 61-year-old Caucasian male who had lived in Florida. He underwent four-vessel coronary artery bypass grafting for coronary artery disease in 1992 with myocardial infarctions and percutaneous coronary interventions. He also had insulin-dependent diabetes mellitus with retinopathy and nephropathy, requiring hemodialysis. His preoperative status was NYHA IV with an ejection fraction of 30–35% and pulmonary hypertension (85/30 mmHg). He underwent HKTx for ischemic cardiomyopathy and end-stage renal disease. His immunosuppressive protocol consisted of antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. Acyclovir and trimethoprim/sulfamethoxazole were given as prophylaxis per transplant protocol. Postoperatively the patient developed delayed kidney allograft function and required hemodialysis. His respiratory condition gradually deteriorated with worsening pulmonary edema despite adequate hemodialysis and right ventricular biopsy negative for rejection. Severe leukocytosis (WBC 12 100–45 300) persisted after the operation despite various therapies. On postoperative day (POD) 27 the patient developed dehiscence at the kidney transplant incision site because of a noninfectious wound seroma and underwent primary surgical repair. In addition, at that time, it was noted that a CMV DNA-PCR performed on the patient was positive for 3700 copies/ml. Acyclovir was discontinued and the patient was started on ganciclovir intravenously. Subsequently, CMV DNA-PCR was decreased to 1000 copies/ml on POD 32, and 375 copies/ ml on POD 35. On POD 28, a chest CT was obtained because of worsening oxygenation, which showed extensive infiltrates consistent with acute respiratory distress syndrome (ARDS). The patient was intubated and underwent bronchoscopy with bronchoalveolar lavage and transbronchial biopsies, which were nonrevealing. In addition, transthoracic echocardiogram was performed on POD 28, which demonstrated preserved left ventricular ejection fraction of 60–65%, moderate right ventricular systolic dysfunction, severe right atrial enlargement and severe tricuspid regurgitation. Three days later, on POD 31, the patient was noted to have hemoptysis and repeat bronchoscopy revealed diffuse hemorrhage. High dose corticosteroids were begun for worsening ARDS and the patient received CMV hyperimmune globulin because of concerns for possible CMV pneumonia. Despite high level mechanical ventilation, the patient’s oxygenation worsened necessitating the addition of nitric oxide. The patient progressively deteriorated with hypotension refractory to pressor support and increasing difficulty with oxygenation. On POD 36, the patient died. Throughout the clinical course, he never developed acute rejection of the transplanted organs as evidenced by multiple biopsies (heart biopsies on POD 6, 13, 20, 28, renal biopsy on POD 8). The postmortem examination revealed Strongyloides stercoralis larvae in the alveoli with accompanying severe bilateral lobar pneumonia and diffuse intra-alveolar hemorrhage (Fig. 1a). Autopsy specimens also revealed numerous S. stercoralis larvae in the transplanted heart and kidney, esophagus, stomach, and small and large bowel, many of them infiltrating through the mucosa and sub-mucosa and some reaching the lymphatic and blood vessels. Strongyloides hyperinfection syndrome is an augmentation of the life cycle, which is medically important because it can lead to overwhelming and disseminated infection in immunocompromised patients including solid organ transplant recipients and carries the potential for high mortality rates (about 70%) [1,2]. In solid organ transplant patients increased corticosteroid dosages is the most frequent risk factor for development of SHS [3,4] and have been associated with the development of the hyperinfection syndrome and dissemination of the organism [5,6]. Meanwhile, not only the reactivation and dissemination of S. stercoralis in recipients but also transmissions of S. stercoralis from deceased donors may be serious problems [7]. There were some reports regarding SHS acquired from the donor in kidney[8], intestinal [7], pancreatic transplantation [9]. Donors and recipients in endemic areas, a history of other helminthic infections,

Invasive Fungal Infections in Lung Transplant Recipients Not Receiving Routine Systemic Antifungal Prophylaxis: 12‐Year Experience at a University Lung Transplant Center

Study Objective. To determine the rate of invasive fungal infection among the lung transplant population at a center that does not provide routine systemic antifungal prophylaxis, and to compare that rate with rates currently reported in the literature.

Majocchi's granuloma after antithymocyte globulin therapy in a liver transplant patient.

A. Gega, G. Ketsela, F.L. Glavin, C. Soldevilla‐Pico, D. Schain. Majocchis granuloma after antithymocyte globulin therapy in a liver transplant patient.
Transpl Infect Dis 2010: 12: 143–145. All rights reserved

Histopathologic resolution of adult liver transplantation adenovirus hepatitis with cidofovir and intravenous immunoglobulin: a case report.

Adenovirus (ADV) infections in adult solid organ transplant recipients, although rare, are associated with high mortality. There are no randomized controlled trials establishing the efficacy of specific treatment modalities. To our knowledge apparent response to treatment with combination therapy with intravenous cidofovir (CDV) and immunoglobulin (IVIG) has only been demonstrated in 2 adult renal transplant recipients in whom ADV was documented in body fluids only. We describe an adult liver transplant recipient diagnosed with ADV hepatitis based on positive immunohistochemical staining of a liver biopsy specimen, positive blood ADV DNA polymerase chain reaction (PCR), and treated with the combination of CDV and IVIG. We demonstrated both clearance of viremia and histopathologic resolution of the hepatitis despite the patients fatal outcome. To our knowledge this is the only case documenting eradication of tissue-invasive ADV disease in any solid organ transplant recipient using CDV and IVIG. This case provides evidence to support the use of this drug combination, which has many potential toxicities that might discourage its use otherwise.