Rate Of Invasive Aspergillosis Research Articles

Anti-Fungal Prophylaxis in Lung Transplant Recipients (LTRs): A Meta-Analysis of Cohort Studies

Purpose Majority of lung transplant centers have adopted antifungal prophylaxis directed against Aspergillus (Asp) species based on single center cohort studies. We performed a meta-analysis to determine whether current antifungal prophylaxis strategies decrease the rate of invasive aspergillosis (IA) or Asp. colonization in LTRs. Methods and Materials The search was carried out on MEDLINE (1990-Oct 2012), EMBASE (1990-Oct 2012). For dichotomous outcomes, relative risks (RR) with 95% confidence intervals (CI) were calculated for individual studies and the summary statistics were calculated using a Random effects model (Review Manager [RevMan] Version 5.0, The Nordic Cochrane Centre, The Cochrane Collaboration, 2008). Results Of 323 references retrieved, 16 retrospective cohort studies were identified. Out of these, 8 studies had sufficient information of the comparator for the meta-analysis. These studies included a total of 1,009 LTRs. Antifungal prophylaxis significantly reduced the IA (RR, 0.45; CI, 0.21-0.97) while there was no significant effect on Asp. colonization (RR, 0.82; CI, 0.56-1.20). Antifungal prophylaxis with inhaled-Amphotericin (including lipid preparation) (3 studies), (RR, 0.47; CI, 0.18-1.22) and azoles (6 studies) (RR, 0.42; CI, 0.12-1.52) didn’t show statistically significant risk reduction. Rate of Discontinuation, cough, SOB, nausea and hepatotoxicity was not statistically significant among different antifungals. Conclusions Overall antifungal prophylaxis decreases the rate of IA however, has no effect on the Asp. colonization in LTRs. A randomized controlled trial to assess the efficacy of antifungal prophylaxis is warranted.

Editorial Commentary: Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients

Invasive fungal diseases, in particular those due to Aspergillus spp., are increasing in incidence and constitute an important cause for morbidity and mortality in children and adolescents with hematologic malignancies and those undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [1]. A contemporary retrospective analysis demonstrated that corticosteroid therapy, neutropenia, immunosuppressive therapy, malignancy, and allogeneic HSCT are the most common risk factors for invasive aspergillosis in pediatric age groups [2]. The overall case fatality rate of invasive aspergillosis in this study was 53%, which is similar to that seen in adult patients. Invasive aspergillosis significantly contributes to the in-house mortality of children with acute lymphoblastic and myeloid leukemia, lymphoma, allogeneic HSCT, and solid organ transplantation. In a retrospective cohort study using a national database of hospital inpatient stays during 2000, 18% (122 of 666) of children with invasive aspergillosis died in the hospital, compared with 1% (1736 of 151 537) of similarly immunocompromised children without invasive aspergillosis [3]. Despite substantial achievements over the past 2 decades, diagnosis and treatment of invasive fungal diseases in children and adolescents are still limited by a number of factors. As a matter of fact, not all antifungal agents are approved in the pediatric population, the appropriate dosage of several drugs has not been established for all age groups, and postmarketing data providing information on safety and efficacy of approved agents under real-life circumstances are scant. Similarly, the value of newer diagnostic tools is not defined in the pediatric population, although they are of major impact for establishing preventive and treatment strategies of invasive aspergillosis [4]. Whereas both the halo sign and the air-crescent sign revealed by pulmonary computed tomography scan are common and highly suggestive for invasive mold infection in adult patients and are included as clinical criteria in the revised definitions of invasive fungal disease set forth by the European Organization for Research and Treatment of Cancer and the Mycosis Study Group (EORTC/MSG) [5], radiographic findings in immunocompromised children with proven pulmonary invasive fungal disease are often nonspecific. In younger children (aged <5 years) in particular, typical signs of pulmonary invasive fungal disease are not seen in the majority of patients. In contrast, multiple nodules or fluffy masses and infiltrates that look like mass lesions are frequently reported [2]. Testing galactomannan (GM), a polysaccharide cell-wall component that is released by all Aspergillus spp. during cell growth, has been evaluated in multiple studies in adults and is included as a microbiological criterion in the revised definitions of invasive fungal disease by the EORTC/MSG consensus group and in a number of Editorial Commentary

Reduction of Invasive Aspergillosis Incidence among Immunocompromised Patients after Control of Environmental Exposure

The objective of the study was to assess the impact of the relocation of an adult hematological intensive care unit on invasive aspergillosis (IA) incidence. A quasi-experimental study, including a control group and an intervention group that both underwent pretest and posttest evaluations, was conducted in the 3 adult hematological intensive care units (each composed of 14 single rooms) in a university hospital from 14 April 2005 through 1 February 2006. One of these units was relocated from the main building to an adjoining modular construction. In this unit, 4 rooms were equipped with laminar airflow before relocation; all rooms were equipped with positive pressure isolation after relocation. The 2 other units (control group), each containing 8 rooms with laminar airflow, did not undergo environmental modification. The diagnostic criteria for IA were based on the criteria of the European Organization for Research and Treatment of Cancer. In total, 356 hospitalized patients were included. Of the 21 cases of IA, 18 were nosocomial, and 3 were of undetermined origin. In the relocated unit, the incidence of IA decreased from 13.2% (9 patients) before relocation to 1.6% (1 patient) after relocation (P=.018). Eight of the 9 patients with IA before relocation stayed in rooms without specific air treatment. The rate of IA did not change in the control group. Patient characteristics were similar in each unit before and after relocation. We detected a straightforward association between environmental modification and decreased IA incidence, which emphasizes the use of an environmental strategy, including high-efficiency air filtration, in the prevention of IA.

Voriconazole Prophylaxis in Lung Transplant Recipients

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole +/- inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A three-fold or higher increase in liver enzymes was noted in 37-60% of patients receiving voriconazole prophylaxis as compared to 15-41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.

TRENDS IN INVASIVE FUNGAL INFECTIONS IN LIVER TRANSPLANT RECIPIENTS

The incidence of invasive fungal infections, particularly invasive candidiasis, after liver transplantation is strongly influenced by surgical factors and technical complexity of the surgery. We assessed the temporal trends in invasive fungal infections in the context of evolution in liver transplantation practices, technical developments, and other risk factors. Demographic and clinical characteristics of the patients, transplantation-related variables, and rates of infection were longitudinally analyzed over the last 10 years in 190 consecutive liver transplant recipients at our institution. Trends for categorical data were evaluated using the Cochran-Armitage trend test and for continuous variables using analysis of variance with linear contrast. A decrease in the length of operation (P=0.03), intraoperative transfusion requirements (P=0.0001), cold ischemic time (P<0.0001), use of roux-en-Y biliary anastomosis (P=0.0015), rate of biopsy proven rejection (P<0.0001), and retransplantation (P=0.056) was documented over the successive years. A significant decline in Child-Pugh score (P=0.02) and in the proportion of patients transplanted as UNOS 2a occurred (P=0.0001). Although the incidence of cytomegalovirus infection remained unchanged, a significant increase in the frequency of primary cytomegalovirus infection (P=0.045), and a decrease in cytomegalovirus disease (P=0.0006) was documented. Over the same time period, a significant decrease in the incidence of invasive candidiasis (P=0.015), and an insignificant increase in the rate of invasive aspergillosis (P=0.20) occurred. Notable technical developments in liver transplantation practices and risk profiles of patients have occurred over the decade. These variables may have a role in influencing the evolving trends in invasive fungal infections in liver transplant recipients.

Invasive Aspergillosis: Focus on New Approaches and New Therapeutic Agents

Infections caused by Aspergillus species are an emerging cause of morbidity and mortality in a variety of immunocompromised patients, despite profound environmental protection and the widespread prophylactic use of agents with anti-Aspergillus activity. At the present time, no firm conclusions can be drawn on the use of chemoprophyla xis, mainly due to the lack of reliable, randomized trials. Therefore, universal prophylaxis should be discouraged and prevention should be targeted towards well-defined high-risk patients, although only as part of a properly designed clinical trial. The crude mortality rate of invasive aspergillosis remains unacceptably high and results at least partly from difficulties in obtaining a reliable diagnosis at an early stage of the disease. The concept of empirical antifungal therapy has been introduced in an effort to overcome these diagnostic obstacles, especially since the early implementation of antifungal therapy appears to be the crucial prerequisite to improve the detrimental outcome of established disease. However, the concept has not been sufficiently validated and is not devoid of significant risks and disadvantages. The implementation of sensitive and predictive new diagnostic tools, such as galactomannan detection, high-resolution pulmonary CT-scanning and detection of aspergillar DNA, may allow a more targeted pre-emptive approach, directed towards the high-risk patients and based upon a battery of clinical, radiological and microbiological clues, though without histopathological proof. The high mortality rate results also from shortcomings of the currently available therapeutic arsenal. Amphotericin B, flucytosine and itraconazole are associated with low success rates and are hampered by serious infusion- or drug-related toxicity, by hazardous drug-drug interactions, by pharmacokinet ic problems and by the development of resistance. In recent years, several companies have launched new compounds into preclinical and clinical trials. Some of these agents target the fungal cell wall in stead of the cell membrane. They exert their action through inhibition of the synthesis of critical compounds of that fungal cell wall, not present in mammalian cells (e.g. inhibitors of β-(1,3)-D-glucan synthesis). This article will focus on new therapeutic approaches (risk-adapted or targeted strategy) and upcoming antifungal agents with anti-Aspergillus activity, in particular voriconazole and caspofungin acetate.