Severe cerebral aspergillosis after liver transplant

V. Leung, A. Stefanovic, D. Sheppard. Severe cerebral aspergillosis after liver transplant.
Transpl Infect Dis 2010: 12: 51–53. All rights reserved
Abstract: Cerebral aspergillosis is a rare complication of liver transplantation. We present the case of a 34-year-old woman with multiple brain lesions discovered 8 days after orthotopic liver transplant for autoimmune hepatitis. The epidemiology, differential diagnosis, diagnostic strategies, and management of cerebral aspergillosis are discussed.     

Invasive aspergillosis in two liver transplant recipients: diagnosis by SeptiFast

Abstract: We report the clinical features, diagnosis, and monitoring findings of invasive aspergillosis (IA) in 2 liver transplant recipients. Blood/serum samples and bronchoalveolar lavage (BAL) fluids were analyzed by a novel commercial polymerase chain reaction (PCR) assay (SeptiFast) and an Aspergillus galactomannan (GM) enzyme-linked immunoassay (EIA). The diagnosis of IA could be performed in <6 h with the detection of Aspergillus fumigatus DNA in blood and BAL fluid. High GM values (mean: 9.1, range: 7.3–10.8) in serum and BAL fluid confirmed the SeptiFast result. Follow-up of the SeptiFast findings and GM index correlated with the clinical course. The molecular detection of A. fumigatus -specific DNA and GM test in blood/serum and BAL samples appears to be a useful tool for prompt diagnosis of IA. Further prospective clinical trials are necessary to evaluate the accuracy of SeptiFast and the GM test in diagnosing IA.     

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients

D. Neofytos, J.A. Fishman, D. Horn, E. Anaissie, C.‐H. Chang, A. Olyaei, M. Pfaller, W.J. Steinbach, K.M. Webster, K.A. Marr. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.
Transpl Infect Dis 2010: 12: 220–229. All rights reserved Abstract: Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received ≥2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12‐week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non‐lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.     

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991–92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community‐acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre‐intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high‐risk solid organ transplant patients.     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

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

S.Y. Park, S.‐H. Kim, S.‐H. Choi, H. Sung, M.‐N. Kim, J.H. Woo, Y.S. Kim, S.‐K. Park, J.‐H. Lee, K.‐H. Lee, S.‐G. Lee, D.J. Han, S.‐O. Lee. Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients.
Transpl Infect Dis 2010: 12: 309–315. All rights reserved Abstract: 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).     

Deep sinus aspergillosis in a liver transplant recipient successfully treated with a combination of caspofungin and voriconazole

We describe the rare case of a diabetic patient who was successfully treated for cytomegalovirus viremia and leishmaniasis following liver transplantation for hepatitis C virus-related cirrhosis, but also developed invasive sinus Aspergillus infection, while still on liposomal amphotericin B (AmBisome). The patient refused radical surgery including eye enucleation, and received a combination of intravenous caspofungin and voriconazole, along with repeated, conservative, local surgical debridement. At follow-up, 15 months after the onset of sinusitis, the patient remains culture-negative, fully active, and without evidence of local recurrence.     

Persistent poor long-term prognosis of allogeneic hematopoietic stem cell transplant recipients surviving invasive aspergillosis

Background Voriconazole treatment increases early survival of allogeneic hematopoietic stem cell transplant recipients with invasive aspergillosis. We investigated whether this survival advantage translates into an increased long-term survival. DESIGN AND METHODS: This retrospective study involved all patients with an invasive aspergillosis diagnosis transplanted between September 1997 and December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point was survival up to 36 months. Survival analysis before and after 12 weeks, as well as cumulative incidence analysis in a competing risk framework, were used to assess the effect of voriconazole treatment and other factors on mortality. RESULTS: Among 87 patients, 42 received first-line voriconazole and 45 received another antifungal agent. Median survival time was 2.6 months and survival rate at 36 months was 18%. Overall, there was a significant difference in the survival rates of the two groups. Specifically, there was a dramatic difference in survival rates up to ten months post-aspergillosis diagnosis but no significant difference after this time. Over the first 36 months as a whole, no significant difference in survival rate was observed between the two groups. First-line voriconazole significantly reduced aspergillosis-attributable mortality. However, first-line voriconazole patients experienced a significantly higher probability of death from a non-aspergillosis-attributable cause. Conclusions Although the prognosis for invasive aspergillosis after stem cell transplantation has dramatically improved with the use of voriconazole, this major advance in care does not translate into increased long-term survival for these severely immunocompromised patients.     

Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients

OBJECTIVES: Invasive fungal infections (IFIs) remain a major cause of infection-related morbidity and mortality following hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: We retrospectively analyzed the incidence of IFIs in 166 patients undergoing either allogeneic or autologous HSCT at our institution between January 2000 and December 2003. RESULTS: Incidence of invasive aspergillosis (IA) and invasive candidiasis among allogeneic HSCT recipients was 23% (16-32%, 95% confidence interval [CI]) and 3% (1-9%, 95% CI), respectively. Duration of neutropenia and reduced-intensity conditioning were the only risk factors for IA in the multivariate model. Patients with IA had significantly reduced overall survival (8% versus 56%, P=0.01) due to higher transplant-related mortality (63% versus 31%, P=0.03). Following autologous HSCT, incidence of IA and invasive candidiasis was 8% (4-19%, 95% CI) and 2% (0.2-11%, 95% CI), respectively. Duration of neutropenia was the only risk factor for the development of IA following autologous HSCT. Overall survival of autologous HSCT recipients with IA was similar to that of patients without IA. Seventeen percent of autologous HSCT recipients were colonized with Candida species. Compared with non-colonized patients these patients had significantly reduced overall survival (72% versus 23%, P=0.004), due to increased treatment-related mortality (23% versus 9%, P=0.02). CONCLUSION: Diagnosis of IA following allogeneic HSCT and Candida colonization in the setting of autologous HSCT defines patient populations with poor outcome but primarily not as a result of the fungal pathogen. Regarding the incidence of IA, duration of neutropenia is the main risk factor, and dose-reduced conditioning is an additional risk factor for the development of IA following allogeneic HSCT, probably owing to increased recipient age in this patient cohort, requiring further studies in this transplantation setting.     

Nosocomial invasive aspergillosis in a heart transplant patient acquired during a break in the HEPA air filtration system

We report a case of nosocomially acquired invasive aspergillosis (IA) in a low-risk heart transplant recipient due to a break in the air conditioning system. A high overload of Aspergillus spores in the intensive care unit room led this patient to acquire IA. Identical environmental and patient isolates allowed our hypothesis to be confirmed and a very precise incubation time to be estimated.     

Epidemiology of fungal infections in solid organ transplant patients

The epidemiology of fungal infection in solid organ transplant patients is of concern due to the high mortality associated with this complication. Rates of fungal infections vary by type of transplant recipient. Most of these infections occur two to six months after transplantation. Liver transplant recipients are more likely to have early fungal infection which is often due to Candida species. Exogenous and endogenous Candida infection may occur in the immunosuppressed patient in the intensive care unit. Patients with chronic rejection are more likely to have late infection (after six months) which may be due to Aspergillus or endemic fungi such as Cryptococcus. Lung and heart–lung transplant recipients are more predisposed to infection with Aspergillus and other filamentous fungi, due to exposure of the transplanted organ to the external environment. Preventative measures such as environmental controls and chemoprophylaxis may be beneficial in high-risk patients. Emerging fungal pathogens such as the dematiaceous fungi may cause skin or soft tissue infection, or more serious systemic infections. Fungal infection should be ruled out in the solid organ transplant patient with early brain abscess. Characteristic risk factors in high-risk types of solid organ transplant recipients should be recognized for early diagnosis and treatment of these infections associated with high morbidity and mortality.     

Changing landscape of invasive aspergillosis in allogeneic stem cell transplant recipients

Abstract: Invasive aspergillosis (IA) is an important infectious complication in allogeneic stem cell transplant (SCT) recipients. Diagnosis of IA has been difficult and often delayed and treatment outcome has been poor, with mortality rates up to 80%. This review summarizes recent developments in this field. There are indications that the incidence of IA may be decreasing due to multiple factors including better understanding of pathogenesis of IA, earlier diagnosis, and various prophylactic and preventive strategies. Recently posaconazole has shown to be effective in reducing the risk of IA in patients treated for graft-versus-host disease (GVHD). Early use of high-resolution thoracic computed tomography assisted with complimentary methods including bronchoalveolar lavage and serum galactomannan determinations are useful in early diagnosis. Our treatment armamentarium against IA has broadened significantly during the last years and there are some indications of improved outcome more recently. On the other hand, increasing use of blood progenitor grafts instead of marrow with higher risk of chronic GVHD, increasing age of SCT recipients, and wide use of donor lymphocyte infusions for treatment of minimal residual disease or relapse may affect to the opposite direction. Despite some promises and improvements, IA will continue to remain a challenge in the upcoming years.