Aspergillosis In Transplant Recipients Research Articles

Pathogenesis of Invasive Pulmonary Aspergillosis in Transplant Recipients

Transplant patients are at high risk for invasive pulmonary aspergillosis, and the associated mortality is high. The purpose of this study is to review the pathogenesis of invasive pulmonary aspergillosis (IPA) in transplant patients. The pathogenesis of aspergillosis is multifactorial and results from a complex interplay between the pathogen and host. It is well recognized that Aspergillus causes IPA in immunocompromised patients. Recent studies have shown that Aspergillus might also cause diseases likely attributed to an unmodulated immune response in certain transplant recipients such as bronchopulmonary aspergillosis or bronchiolitis obliterans syndrome in lung transplant recipients. This review focuses on two crucial axes of the damage response framework applicable to aspergillosis: (1) Aspergillus virulence attributes that enable it to survive and proliferate in the host (thermotolerance, stress and hypoxic response, secretion of secondary metabolites) and (2) host response with specific focus on innate immunity and angiogenesis.

AspergillusTracheobronchitis Causing Subtotal Tracheal Stenosis in a Liver Transplant Recipient

Invasive aspergillosis is recognized as one of the most significant opportunistic infections after liver transplantation. Diagnosis of invasive aspergillosis in transplant recipients has been proven to be challenging, and optimal approach to the treatment of invasive aspergillosis is still controversial. We here present an unusual case of Aspergillus tracheobronchitis in the setting of liver transplantation. A 47-year-old female patient with persistent dry cough after liver transplantation developed respiratory insufficiency and was readmitted to the intensive care unit 55 days after liver transplantation. A CT scan revealed subtotal tracheal stenosis; bronchoscopy was performed, and extended white mucus coverings causative of the tracheal stenosis were removed. Microbiological assessment isolated Aspergillus fumigatus. The diagnosis was obstructive Aspergillus tracheobronchitis. The patient was started on a treatment of voriconazole 200 mg orally twice daily, adjusted to a trough level of 1–4 mg/L. For further airway management, a tracheal stent had to be implanted. The patient is alive and well 28 months after liver transplantation. Invasive aspergillosis should be considered a possible etiology in liver transplant patients presenting with unspecific symptoms such as persistent dry cough. Optimal strategies for improved and early diagnosis as well as prophylaxis need to be defined.

A systematic review of validated methods for identifying infection related to blood products, tissue grafts, or organ transplants using administrative data

To systematically review algorithms to identify infections related to blood products, tissue grafts, or organ transplants in administrative and claims data, focusing on studies that have examined the validity of the algorithms. A literature search was conducted using PubMed and the database of the Iowa Drug Information Service. Reviews were conducted by two investigators to identify studies using data sources from the USA or Canada because these data sources were most likely to reflect the coding practices of Mini-Sentinel data sources. Searches identified one study that examined the validity of an algorithm to identify aspergillosis in transplant recipients and 16 studies that used nonvalidated algorithms to identify infections in recipients of blood products, tissue grafts, or organ transplants. Transfusion was studied as a risk factor for infection, but no studies attempted to identify infection transmitted by any of the exposures under review. Two studies reported sensitivity ranging from 21% to 83% and specificity of 100% of codes to identify allogeneic blood transfusion. No validation studies of algorithms to identify tissue grafts or organ transplant were identified. There is little evidence to support the validity of algorithms to identify infections related to blood products, tissue grafts, or organ transplants in administrative data or algorithms to identify the exposures. Although it may be possible to validate algorithms to identify the exposures and infectious outcomes, the use of administrative data to identify infections transmitted by these exposures may be challenging. Codes indicating infections acquired through medical care may be useful.

Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients

Invasive pulmonary aspergillosis (IPA) is an important cause of mortality in transplant recipients and in patients with neutropenia. Although IPA has been studied extensively in neutropenic patients, there are limited data on IPA in recipients of solid organ transplants (SOTs). We compared the clinical features and radiologic findings of 27 SOT recipients with IPA with those of 35 neutropenic patients with IPA. The SOT recipients were more likely than neutropenic patients to show peribronchial consolidation (31% vs. 7%; P=0.03) or ground-glass opacity (38% vs. 7%; P=0.007) and less likely to have fever (22% vs. 80%; P<0.001), macro-nodules (35% vs. 67%; P=0.02), mass-like consolidation (27% vs. 67%; P=0.004), halo signs (8% vs. 56%; P<0.001), or air-crescent signs (0% vs. 22%; P=0.01).

Insidious sinusitis leading to catastrophic cerebral aspergillosis in transplant recipients

Cerebral aspergillosis is an important cause of mortality in organ transplant recipients and is typically associated with concomitant pulmonary infection.1 Herein we describe two patients with insidious Aspergillus sinusitis leading to catastrophic CNS infection. ### Case reports. #### Patient 1. A 56-year-old man with pancreas and kidney transplant was transferred to our tertiary care facility with meningoencephalitis and cerebral infarction. He had a history of new onset headache of 6 weeks with fever. His immunosuppressive regimen consisted of mycophenolate mofetil, prednisone, and tacrolimus with prophylactic sulfamethoxazole/trimethoprim and valganciclovir. He had a temperature of 38.9 °C, opened eyes to voice only but followed commands, and neurologic examination showed neck stiffness, dysarthria, right-sided anisocoria, and a left sided hemiparesis. Empiric antimicrobial therapy was started, including fluconazole. CT showed fluid and membrane thickening within paranasal sinuses. Cranial MRI demonstrated enhancement involving the basilar meninges and sphenoid sinus (figure, A). Diffusion-weighted images demonstrated restricted diffusion in the right pons, right cerebellum, and right caudate head consistent with acute infarction (figure, B). Cerebral angiogram demonstrated narrowing of arteries around the basal cisterns and occlusion of the right superior cerebellar artery, consistent with vasculitis secondary to basal meningitis. Lumbar puncture (LP) revealed CSF leukocytes of 1,200/mm3 (94% neutrophils), protein of 73 g/L, and glucose of 64 mg/dL. Fluconazole was changed to voriconazole. Cultures of CSF remained negative. The serum galactomannan antigen test was normal (0.39 index), …

Caspofungin as First-Line Therapy for the Treatment of Invasive Aspergillosis After Thoracic Organ Transplantation

Although amphotericin was the gold standard in the treatment of invasive aspergillosis in transplant recipients, nephrotoxicity and lack of efficacy often limits its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressant trough levels significantly. We report our first clinical experience with the use of caspofungin as first-line therapy in heart and lung transplant recipients with invasive aspergillosis. Caspofungin was administered at 50 to 70 mg/day in heart and lung transplant recipients with renal impairment while invasive aspergillosis was diagnosed and classified. Aspergillus serology, serologic inflammatory markers, and X-rays were taken to monitor infectious activity. Creatinine and immunosuppressant trough levels were monitored closely. Invasive aspergillosis was diagnosed by chest X-ray, serology, and positive sputum in 1 heart-lung, 7 heart, and 4 single-lung transplant recipients, and caspofungin was administered for a mean time of 21 +/- 9 days. Basic immunosuppressants were tacrolimus in 9 patients or cyclosporine in 3. Complete remission was achieved in 10 patients (83%). Adverse effects of caspofungin were fever in 6, diarrhea in 3, and neutropenia in 1. Renal function remained stable (3.2 +/- 1 mg/dl before vs 2.3 +/- 0.9 mg/dl after, p = 0.07). Trough levels of all immunosuppressants did not change significantly during caspofungin treatment (10.9 +/- 4.1 ng/ml before vs 9.9 +/- 4.0 ng/ml after [p = 0.31] for tacrolimus; 214 +/- 98 ng/ml before vs 229 +/- 88 ng/ml after [p = 0.41] for cyclosporin A), while the administered dosage remained stable. In heart and lung transplant recipients with invasive aspergillosis, caspofungin seemed to be an effective anti-fungal agent with a promising safety profile. Further prospective randomized trials are needed to investigate an advantageous role of caspofungin in the treatment of invasive aspergillosis.

Invasive aspergillosis in organ transplant recipients: new issues in epidemiologic characteristics, diagnosis, and management

Changing transplantation practices, novel immunosuppressive protocols, and evolving recipient characteristics have led to notable changes in the epidemiology of invasive aspergillosis in transplant recipients. The frequency of disseminated infection and of central nervous system involvement has declined significantly in organ transplant recipients in the recent years. Amongst variables that may have contributed to these trends is an overall lesser severity of illness of transplant recipients in the current era. Calcineurin-inhibitor immunosuppressive agents may also have had a role in altering the disease course and the risk of dissemination. A new paradigm in the management of post-transplant immunosuppression is the use of calcineurin-inhibitor and corticosteroid sparing regimens by pretreatment of the recipient with T-cell depleting agents (Campath 1-H or thymoglobulin) and utilization of minimal post-transplant immunosuppression. The impact of these potent lymphoablative regimens on opportunistic mycoses in organ transplant recipients remains to be fully discerned. Although still unacceptably high, the mortality rate in organ transplant recipients with invasive aspergillosis in the current era appears to have declined. A focus of a great interest and controversy is the use of combination therapy for invasive aspergillosis in transplant recipients.

Invasive aspergillosis in transplant recipients.

From the Infectious Disease Section, VA Medical Center, Pittsburgh, Pennsylvania. Address reprint requests to: Nina Singh, Infectious Disease Section, VA Medical Center, University Drive C, Pittsburgh, PA 15240. Fax: 412-688-6950.