Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality.

Background: Invasive aspergillosis (IA) is a leading cause of infection-related mortality following hematopoietic cell transplantation (HCT). The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time.

Methods: Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included.

Emergence of opportunistic mould infections in the hematopoietic stem cell transplant patient.

Infection due to opportunistic moulds is an emerging problem in hematopoietic stem cell recipients. Through the 1990s, the incidence of invasive aspergillosis in allogenic graft recipients climbed steadily, peaking at 10% to 15%. In this decade, other opportunistic mould infections are emerging, including zygomycosis, fusariosis, and scedosporiosis.

Resistant Microascus cirrosus pneumonia can be treated with a combination of surgery, multiple anti-fungal agents and a growth factor.

A 49-year old male with acute myelogenous leukemia relapsed eight years post allogeneic bone marrow transplantation. The patient received induction chemotherapy causing prolonged neutropenia. The patient developed pneumonia for which empirical antibacterial and antifungal therapy were started.

Molecular studies reveal frequent misidentification of Aspergillus fumigatus by morphotyping.

Aspergillus fumigatus has been understood to be the most common cause of invasive aspergillosis (IA) in all epidemiological surveys. However, recent studies have uncovered a large degree of genetic heterogeneity between isolates morphologically identified as A. fumigatus, leading to the description of a new species, Aspergillus lentulus.

GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence.

Gliotoxin is a nonribosomal peptide produced by Aspergillus fumigatus. This compound has been proposed as an A. fumigatus virulence factor due to its cytotoxic, genotoxic, and apoptotic properties.

Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20-40% of CF patients and are of unclear clinical significance.

Aspergillosis: spectrum of disease, diagnosis, and treatment.

Infections by Aspergillus species present a particular challenge. The organism, which is ubiquitous in the environment, causes allergic disease in otherwise healthy individuals and devastating disease in the immunosuppressed. This article examines the range of infections caused by Aspergillus species, the challenges of diagnosis, and current treatment options.

Nicotine administration effects on feeding and cocaine-amphetamine-regulated transcript (CART) expression in the hypothalamus.

In previous studies food intake and meal size significantly decreased in rats two days after injecting 4 mg/kg/day nicotine tartrate. Food intake returned to normal after nine days of continued nicotine treatment, when reduced meal size is countered by an increase in meal number. Nicotine also reduced body weight after nicotine injection and body weight remained low after nine days.

Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin during therapy.

Clinical failure associated with reduced susceptibility to caspofungin has been described in Candida albicans and C. parapsilosis. We report a case of Candida krusei infection that progressed despite caspofungin therapy.

Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: A retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT.

Aspergillus ustus infections among transplant recipients.

Aspergillus ustus is a mold that rarely infects humans; only 15 systemic cases have been reported. We report the first outbreak of invasive infection caused by A. ustus among hematopoietic stem cell transplant (HSCT) recipients.

Contemplating the murine test tube: lessons from natural killer cells and Cryptococcus neoformans.

Murine experimentation has provided many useful tools, including the ability to knockout or over-express genes and to perform experiments that are limited by ethical considerations. Over the past century, mice have imparted valuable insights into the biology of many systems, including human immunity. However, although there are many similarities between the immune response of humans and mice, there are also many differences; none is more prominent than when examining natural killer cell biology.

Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis.

Background: Micafungin (FK463) is a new lipopeptide compound (echinocandin) with activity against Aspergillus and Candida species. This study evaluated the safety and efficacy of micafungin in patients with proven or probable invasive aspergillosis (IA).

Methods: A multinational, non-comparative study was conducted to examine proven or probable (pulmonary only) Aspergillus species infection in a wide variety of patient populations.

Clinical significance of azole antifungal drug cross-resistance in Candida glabrata.

Candida glabrata, which can become resistant to fluconazole, is a common cause of bloodstream infection. This study was performed to determine the significance of cross-resistance to new azole drugs among C. glabrata isolates recovered as a cause of infection in azole-treated hematopoietic stem cell transplant (HSCT) recipients.

Using the Cancer Rehabilitation Questionnaire in patients with colorectal cancer.

This article describes the development and testing of the Cancer Rehabilitation Questionnaire (CRQ) in patients with colorectal cancer. A descriptive, correlational survey was conducted in a sample of patients with colon or rectal cancer who received care at an outpatient cancer clinic at a large, northeastern U.S.

Comparison of three methodologies for the determination of pulmonary fungal burden in experimental murine aspergillosis.

Quantitative culture, quantitative PCR and the galactomannan enzyme immunoassay (EIA) were compared for their ability to determine the pulmonary fungal burden in a murine model of invasive aspergillosis. Quantitative culture of specimens containing hyphae under-represented the absolute fungal burden in established infection when compared with the two other methods. The best correlation was observed between the two non-culture methods.

Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states.

Aspergillus fumigatus is a common cause of invasive and allergic pulmonary disease. Resting conidia of the filamentous fungus are constantly inhaled, but cause infection only after initiating hyphal growth. In this study, we have explored whether macrophages can distinguish between resting spores and the maturing, potentially invasive form of the fungus.

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections.

Mistaken identity: Neosartorya pseudofischeri and its anamorph masquerading as Aspergillus fumigatus.

Invasive fungal infections caused by Neosartorya pseudofischeri S. W. Peterson [anamorph Aspergillus thermomutatus (Paden) S.

LaeA, a regulator of morphogenetic fungal virulence factors.

Opportunistic animal and plant pathogens, well represented by the genus Aspergillus, have evolved unique mechanisms to adapt to and avoid host defenses. Aspergillus fumigatus, an increasingly serious pathogen owing to expanding numbers of immunocompromised patients, causes the majority of human infections; however, an inability to identify bona fide virulence factors has impeded therapeutic advances. We show that an A.

Reproducibility of low galactomannan enzyme immunoassay index values tested in multiple laboratories.

The Platelia galactomannan enzyme immunoassay is a commercially available nonculture method for diagnosing invasive aspergillosis. Recently, steps have been taken to improve sensitivity; specifically, a low (0.5 to 0.

Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program.

The incidence of invasive aspergillosis was estimated among 4621 hematopoietic stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites dispersed throughout the United States, during a 22 month period from 1 March 2001 through 31 December 2002. Cases were identified using the consensus definitions for proven and probable infection developed by the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis was calculated for the first episode of the infection that occurred within the specified time period after transplantation.

Design issues in studies evaluating diagnostic tests for aspergillosis.

Although invasive aspergillosis is recognized as an increased concern for immunosuppressed patients, establishing an early diagnosis remains a challenge. Current methods for diagnosis, including sensitive radiography and invasive procedures to identify organisms in affected tissues, provide an early diagnosis for only a small proportion of patients infected with Aspergillus species. The availability of a standardized assay to detect circulating Aspergillus galactomannan, the BioRad Platelia Aspergillus galactomannan enzyme immunoassay, should be considered as a valuable tool.

Scedosporium/Pseudallescheria infections.

The genus Scedosporium comprises a group of filamentous fungi found ubiquitously in the environment. The two major human pathogens within this genus are S. apiospermum-the asexual state of Pseudallescheria boydii-and S.