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PubMed2006

Topical voriconazole solution for cutaneous aspergillosis in a pediatric patient after bone marrow transplant.

Invasive aspergillosis seems to be on the rise, especially in immunocompromised children. Historically, only systemic amphotericin B has been effective against Aspergillus. Development of newer antifungal agents, such as voriconazole and caspofungin, has improved the treatment options available for aspergillosis, although no definitive management strategy has been established. Here we describe the use of topical voriconazole combined with systemic antifungal agents for cutaneous aspergillosis in a pediatric patient after bone marrow transplant.

Administration, Cutaneous↗
PubMed2004

Immunohistochemical detection of fungal elements in the tissues of goslings with pulmonary and systemic aspergillosis.

Nineteen goslings with pulmonary and systemic aspergillosis were the subject of the study. The lungs and air sacs were the main sites affected by the disease, and were generally characterised by diffuse yellowish-white granulomas. In 7 cases with pulmonary and air-sac involvement the granulomas were scattered to the serosal linings of the gastrointestinal and upper respiratory tracts, to the liver, spleen and kidneys, and in two cases also to the bursa of Fabricius, musculus (m.) longus colli and adventitia of aorta. The granulomas were often characterised by a necrotic centre surrounded by heterophils, macrophages, lymphocyte and plasma cells, and in late granulomas by multinucleated foreign-body giant cells, and again by an outer thin fibrous capsule. Numerous fungal hyphae were found within the necrotic debris of the granulomas by Gridley and PAS staining techniques. Immunohistochemistry reliably confirmed aspergillosis in all of the cases. Fungal elements in the lungs of goslings severely affected by the disease stained heavily within the centre of the granulomas, whereas few antigens reacted in the chronic cases. Fungal fragments, which were not discernible using routine fungal stains, reacted clearly in the cytoplasm of macrophages and giant cells. Thus, although fungal elements within the granulomas were histologically indicative of aspergillosis, immunohistochemistry also had to be applied to obtain a definitive diagnosis of the disease and to differentiate it from many of the filamentous fungi.

Animals↗
PubMed2005

Invasive pulmonary aspergillosis.

In susceptible patients, invasive aspergillosis has a high incidence and a mortality of up to 80%. The diagnosis of this condition is difficult, especially in the early stages of the disease and, as a consequence, antifungal therapy, despite its expense and toxicity, is often initiated empirically. Until recently, there were very few effective antifungal agents for established invasive aspergillosis, but the introduction of two new drugs, voriconazole and caspofungin, has increased the treatment options. These newer antifungal therapies, combined with improved early diagnosis due to the introduction of newer microbiologic techniques, offer the hope that there will be a significant improvement in the substantial morbidity and mortality associated with invasive aspergillosis over the next 5 years.

Antifungal Agents↗
PubMed1992

[Invasive aspergillosis of the sphenoid sinus and paralysis of the 6th nerve].

A case of aspergillosis of the sphenoid sinus manifested as an isolated sixth nerve palsy occurred in a 74-year old diabetic woman who had no complaints of headache or symptoms suggestive of sinusitis. A CT scan demonstrated a large mass occupying the sphenoid and ethmoid sinuses extending posteriorly to the clivus. There was a calcific density within the opacified sinus and bony erosion of the sphenoid walls and the sella turcica. The patient underwent a sublabial transseptal sphenoidotomy with removal of necrotic material and debridement of the surrounding tissue. Histologic examination revealed granulation tissue with chronic inflammatory cells and abundant dichotomously branching hyphae. Postoperatively the patient was given amphotericin B and 5-fluorocytosine. Three months later the sixth nerve palsy had completely cleared and the patient had no other complaint. Sphenoid sinus aspergillosis is a rare disease and may have variable clinical manifestations according to involvement of different structures located closely to the sinus. Our patient developed an isolated sixth nerve palsy which was at onset considered to be caused by diabetes. Computerized tomography scans disclosed abnormalities strongly indicative of invasive aspergillosis. It illustrates the need of appropriate work-up in cases of an isolated sixth nerve palsy even in patients with diabetes or other risk factors.

Abducens Nerve↗
PubMed1999

Combination antifungal therapy for invasive aspergillosis infection in liver transplant recipients: report of two patients.

Invasive aspergillosis in solid organ transplant recipients is associated with mortality of approximately 100%. The search for optimal therapy has led clinicians to administer antifungal combinations. Two orthotopic liver transplant recipients developed invasive aspergillosis (pulmonary and perivertebral) after transplantation and were treated with combination antifungal therapy consisting of liposomal amphotericin B and itraconazole. Although both patients were initially stabilized, they died after 94 and 138 days of antifungal therapy, respectively. Presumably, aspergillosis was the principal cause of death. Antifungal serum concentrations and fungicidal titers in both patients indicated that the drugs may have been antagonistic and thus detrimental.

Adult↗
PubMed2003

Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis.

Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal cell wall synthesis). Caspofungin (Cancidas), Caspofungin MSD) is the first echinocandin to be approved and is administered intravenously. Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole 200 mg/day and was at least as effective as intravenous amphotericin B 0.5 mg/kg/day in patients with oesophageal candidiasis in two randomised, double-blind studies. A favourable combined clinical and endoscopic response occurred in 81% of caspofungin recipients versus 85% of fluconazole recipients and in 74% of caspofungin recipients versus 63% of amphotericin B recipients. A favourable combined response rate of approximate, equals 90% and approximate, equals 60% occurred in the stratum of patients with oesophageal candidiasis who received caspofungin or amphotericin B in a third randomised, double-blind study. Caspofungin (70 mg loading dose followed by 50 mg/day) had similar efficacy to intravenous amphotericin B (0.7-1.0 mg/kg/day in patients with neutropenia and 0.6-0.7 mg/kg/day in patients without neutropenia) in patients with invasive candidiasis in a double-blind, randomised trial. A favourable overall response occurred in 73.4% of caspofungin recipients and in 61.7% of amphotericin B recipients. In a noncomparative study, salvage therapy with caspofungin (70 mg loading dose followed by 50 mg/day) was effective in patients with invasive aspergillosis who were refractory to or did not tolerate standard antifungal therapy. A favourable response (complete plus partial response) occurred in 37 of 83 patients (45%). Caspofungin was generally well tolerated in clinical trials; it had similar tolerability to intravenous fluconazole and was better tolerated than intravenous amphotericin B. Significantly fewer caspofungin than amphotericin B recipients reported chills, fever, nausea or infusion-related adverse events. In conclusion, caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative trials, caspofungin had similar efficacy to fluconazole and was at least as effective as amphotericin B in oesophageal candidiasis and had similar efficacy to amphotericin B in invasive candidiasis. In addition, caspofungin had similar tolerability to fluconazole and was better tolerated than amphotericin B in these indications. Caspofungin was also effective in patients with invasive aspergillosis who were refractory to or intolerant of standard antifungal agents. Thus, caspofungin provides an alternative to triazoles or amphotericin B in oesophageal candidiasis and an alternative to amphotericin B in invasive candidiasis, as well as being an effective salvage therapy in invasive aspergillosis.

Animals↗
PubMed1996

Empyema following the percutaneous instillation of antifungal agents in patients with aspergillosis.

We report two cases of empyema as a complication of the percutaneous instillation of antifungal drugs for pulmonary and pleural aspergillosis. Case 1 underwent percutaneous administration of amphotericin B and fluconazole for 2 months. Six months later, the patient was found to have an Aspergillus empyema with a bronchopleural fistula. Case 2 with pulmonary and pleural aspergillosis underwent percutaneous administration of amphotericin B for one month. Four months later, the patient underwent pleural drainage due to empyema. Pleural biopsy revealed pleural aspergillosis. In both cases, it was suggested that the preceding Aspergillus infection and percutaneous instillation of antifungals resulted in the development of empyema.

Aged↗
PubMed1997

Polymerase chain reaction amplification of Asp f I and alkaline protease genes from fungus balls: clinical application in pulmonary aspergillosis.

Asp fI(18 kDa) and alkaline protease (33 kDa) are the 2 major antigens which are derived from Aspergillus (A.) fumigatus and have been implicated as possible virulence factors in the pathogenesis of Aspergillus-induced diseases. We attempted to detect fragments of genes encoding both proteins from fungus balls obtained at surgery or autopsy by polymerase chain reaction (PCR) amplification and then used PCR to test clinical samples. Frozen-stored fungus ball samples from a patient with acute myeloid leukemia complicated by Aspergillus pneumonia and from a patient with pulmonary aspergilloma were studied. We successfully amplified a 315 bp PCR product, the target sequence for Asp f I, and a 747 bp PCR product as a target sequence for alkaline protease (ALP) in both cases. In addition, 13 clinical samples including sputum specimens from patients with pulmonary aspergillosis were also examined. PCR analysis for the Asp f I (ALP) gene in clinical samples showed positive results in 5/10 (6/10) patients with pulmonary aspergilloma and in 3/3 (1/ 3) patients with invasive pulmonary aspergillosis. Culture data on A. fumigatus revealed positive results in 3/9 patients with pulmonary aspergilloma and in 2/3 patients with invasive pulmonary aspergillosis. This method can be used to recognize the involvement of A. fumigatus in various clinical settings where conventional culture results are not readily available.

Adult↗
PubMed1999

Successful treatment of cerebral aspergillosis with a high oral dose of itraconazole after excisional surgery.

We report a case of cerebral aspergillosis which originated from the sphenoid sinus, and involved a progressive decrease of visual acuity. The neurological signs indicated a cavernous sinus invasion. After extensive intracranial surgery we treated the residual aspergillosis with a high oral dose of itraconazole (800 mg/d for 4 months, followed by 400 mg/d for 5 months). The neurological impairments of the patient gradually subsided with the resolution of the fungal lesion shown on MRI. The successful therapy indicated that itraconazole has a significant role in the treatment of advanced cerebral aspergillosis if it is used in high doses (16 mg/kg/d for adults).

Administration, Oral↗
PubMed2001

Invasive pulmonary aspergillosis with thrombosis in the left atrium.

We report a female patient with left atrial wall invasion from pulmonary aspergillosis. She had been treated for diabetes mellitus. Pulmonary aspergillosis extended to the left atrial wall via the left pulmonary vein and formed a polypoid lesion in the left atrium. The polypoid lesion was composed of thrombus, and the thrombus increased in size to become large, and it showed invagination into the mitral valve during diastole. We considered that the thrombus was formed on the injured endocardium. Severe invasive aspergillosis thus could occur in a mild systemic immunocompromised host.

Aspergillosis↗
PubMed2006

Chemokines in allergic aspergillosis--from animal models to human lung diseases.

Allergic bronchopulmonary aspergillosis (ABPA) is a frequent syndrome in patients with cystic fibrosis (CF) or asthma. Animal models revealed distinct roles for the chemokines CCL2, CCL3, CCL5, CCL6, CCL17 and CCL22 and their receptors in the pathogenesis of allergic aspergillosis. In humans, serum levels of the CCR4 ligand CCL17 identified ABPA in patients with CF or asthma, suggesting CCL17 as novel diagnostic marker and future therapeutical target in ABPA. This review illustrates the manifold role of chemokines in animal models of allergic aspergillosis and translates these findings to human lung diseases.

Animals↗
PubMed1990

Aspergillosis of the central nervous system causing subarachnoid hemorrhage from mycotic aneurysm of the basilar artery--case report.

The authors present an extremely rare case of aspergillosis of the central nervous system (CNS) causing subarachnoid hemorrhage (SAH). A 78-year-old female developed facial pain, progressive deterioration in left visual acuity, and left total ophthalmoplegia. Computed tomography demonstrated a heterogeneously enhanced mass extending from the sphenoid sinus to the left cavernous sinus and left orbit, and angiography showed luminal narrowing and irregularity of the left internal carotid artery at its siphon. Biopsy of the left orbital and sphenoid sinus mass resulted in the diagnosis of Aspergillus granuloma. Despite combined administration of amphotericin-B and 5-FC, she became comatose from brainstem infarction and finally, suddenly died. Postmortem examination revealed massive SAH due to a ruptured mycotic aneurysm of the basilar artery. Aspergillosis of the CNS is a growing problem with the wider use of immunosuppressants and antibiotics. To the authors' knowledge, however, only 13 cases of CNS aspergillosis causing SAH have been reported. The prognosis is absolutely bad, with all patients dying from rupture of major intracranial arteries such as the internal carotid artery and basilar artery. Early diagnosis and vigorous chemotherapy are important.

Aged↗
PubMed1984

Serological tests in the diagnosis of pulmonary aspergillosis.

Sera from 44 patients with clinically suspected pulmonary aspergillosis (mainly of an allergic type) were examined for antibodies to Aspergillus fumigatus using an enzyme-linked immunosorbent assay (ELISA) and counter-immunoelectrophoresis (CIE). Of the sera, 15 were considered to contain Aspergillus antibodies using ELISA; 11 of these also contained precipitins by CIE. In no instance was a CIE-positive serum negative by ELISA. The serum of 1 patient with autopsy-verified invasive pulmonary aspergillosis was negative in both tests. Protein-enriched antigens derived by ammonium sulphate precipitation of crude hyphal homogenates seemed of most use in ELISAs. In addition, 4 of 8 sera obtained from patients with possibly invasive candidosis also revealed significant levels of Aspergillus antibody by ELISA (but not CIE). All of the 8 sera contained readily detectable Candida precipitins by CIE. Problems of potential cross-reactivity obviously need careful consideration with ELISAs. Our results suggest that ELISA procedures under appropriately controlled conditions are more sensitive than CIE for detecting Aspergillus antibodies. However it seems that some patients with invasive aspergillosis will be antibody-negative even with sensitive tests such as ELISA.

Antibodies, Fungal↗
PubMed1996

Nosocomial cerebral aspergillosis: a report of 3 cases.

Cerebral aspergillosis carries a mortality rate close to 100%, especially in immunocompromised patients. We describe 3 patients who contracted cerebral aspergillosis after neurosurgery, 2 of whom survived after exhaustive surgical treatment and medical treatment with high doses of amphotericin B (once liposomal), 5-fluorocytosine and itraconazole. We review the few non-fatal cases of cerebral aspergillosis reported. We consider that surgical excision must be complete and repeated if necessary, always in combination with medical treatment.

Adolescent↗
PubMed1987

Pathogenetic and serological aspects of pulmonary aspergillosis.

Af is an important pathogen of the bronchopulmonary system, and the clinical spectrum encompasses aspergilloma, CNPA, IPA, ABPA, bronchial asthma, and allergic alveolitis. Bronchial carriage may, however, not always be associated with pathological effects. The polymorphism of the aspergillus-related disorders seems mostly to depend upon the different responses of the hosts. This review considers the antigenic composition of Af and specific antibody responses in man in relation to the pathogenesis and diagnosis of the various forms of pulmonary aspergillosis. More than 200 macromolecular components have been listed for Af and more than 30 antigens found to react with human sera. Serum antibodies to Af are common in healthy subjects. Schønheyder and his associates (A-L) have shown that IgG, IgA and IgM antibodies in healthy subjects are directed towards antigens to which also patients with aspergillosis strongly react. With immunofluorescent staining these antigens were found to be associated with hyphal walls, and a MW 470,000 fraction from ruptured mycelium was most reactive in ELISA. The respiratory tract appears to be the major route for exposure since the humoral responses include IgA class antibodies, and sIgA antibodies are found in bronchial secretions. Moreover, IgG antibody levels to the MW 470,000 fraction correlate with occupational exposure and smoking habits. In patients with cystic fibrosis high IgG antibody levels to MW 470,000 and MW 25,000-50,000 antigen fractions were associated with the carriage of Af in the sputum. An individual patient's level of IgA antibodies to the MW 470,000 fraction was inversely related to the Af carrier rate, and this was also true for IgE dependent reactivity to Af antigens. These observations indicate that IgG antibodies to some antigens mirror the extent of antigenic exposure, whereas some IgA and IgE antibodies may play a protective role against bronchial colonization with Af. IgG antibody determinations by ELISA were found to provide a higher diagnostic efficacy in pulmonary aspergillosis than IgA antibody assays. With IgG antibodies there were statistically significant differences between patients and the controls and there was little overlap of ELISA values between the groups. The fractions of MW 250,000 with catalase activity and MW 25,000-50,000 with protease activity, were most suitable for serological diagnosis. A gel immunoelectrophoretic assay proved Af catalase to be a major diagnostic antigen in patients with aspergilloma or with an apical aspergillus lung infiltrate.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Fungal↗
PubMed2000

[An autopsy case of HELLP syndrome with disseminated aspergillosis].

Disseminated aspergillosis is an uncommon and unpredictable complication in severely immunocompromised patients and poses a challenging problem in the management and care of seriously ill patients receiving intensive care therapy. We report an autopsied case of disseminated aspergillosis occurring ina 31-year-old female patient who was treated for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. She initially presented with edema and proteinuria at a pregnancy check-up. At gestational age 33 weeks and 2 days, she had right lower abdominal pain, nausea, and jaundice. The next day she delivered a male neonate transvaginally, followed by excessive postpartum uterine bleeding. Although an emergency hysterectomy was performed, her hemorrhagic diathesis could not be controlled even after transcatheter embolization of the internal iliac arteries with subsequent ligation and repeated blood transfusions totalling to 31,070 ml. She eventually died of a cerebral hemorrhage 21 days after the parturition. Autopsy showed generalized jaundice and petechiae, as well as extensive hemorrhage observed in the abdominal wall, peritoneal cavity, and retroperitoneal and pelvic spaces. In addition,there were multifocal hemorrhages found in the left temporal, right frontal and posterior lobes of the cerebrum, and pons. Disseminated aspergillosis was found in the lungs, trachea, brain, esophagus, stomach, heart, and thyroid gland. These findings suggest that systemic postoperative complications, associated with massive blood transfusions and hepatic failure, mutually contribute to the overall deterioration of host defense mechanism, and may underlie the occurrence of devastating systemic fungal infection.

Adult↗
PubMed2006

[Clinical analysis of chronic pulmonary aspergillosis and discovery of an elastase inhibitor].

We studied the clinical features of 59 chronic pulmonary aspergillosis cases (aspergilloma, chronic necrotizing pulmonary aspergillosis) which we experienced in our hospital. To diagnose this disease, X-rays, sputum culture and serologic tests were mainly examined, X-ray findings were a fungus ball type in 47% of cases and thickened wall of a cavity type in 32%. Positive sputum culture found was A. fumigatus 78%, A. niger 13% and A. flavus 2%. Positive rates of serologic tests showed precipitating antibody 81% and antigen 11%; 39% of beta-D glucan exceeded the reference value. As clinical symptoms, bloody sputum and hemoptysis were found at high frequency. Antifungal agents were administered intravenously or topically for treatment, primarily AMPH-B, ITCZ and MCFG. As adjuvant therapy, we administered Ulinastatin which is an elastase inhibitor for use against hemoptysis, and we performed steroid combination for cases considered to be associated with allergy. In all of 6 cases of chronic necrotizing pulmonary aspergillosis which were administered MCFG, X-ray findings improved. A pathogenic factor, elastase was isolated from Aspergillus spp., and we also found the elastase inhibitor from this series. Five of 12 strains of A. fumigatus, and one of 2 strains of A. flavus expressed elastase inhibitory activity when we screened for the culture supernatant of various Aspergillus spp. of a clinical isolate. Elastase inhibitory activity from A. niger was very weak. Culture supernatants from 5 strains of A. fumigatus and one strain of A. flavus were stable for a fever, and human leucocyte elastase was inhibited, but these did not inhibit porcine pancreas elastase. We are aiming at clinical application and plan to continue further study.

Adult↗
PubMed1989

Aspergillosis of the paranasal sinuses--diagnostic significance of the computed tomography.

Aspergillosis of the paranasal sinuses appears to be relatively rare in occurrence, but there is a growing incidence of it in accordance with the increasing use of antibiotics, steroid hormones, anticancer drugs, and radiation therapy. We have seen 15 cases of aspergillosis of the paranasal sinuses in which computed tomography (CT) was helpful for diagnosis. The characteristic feature of CT findings was the intermixture of high and low density areas in the affected paranasal sinuses, apparently caused by increased X-ray absorption due to calcification. These findings indicate that CT is useful in the preoperative diagnosis of aspergillosis of the paranasal sinuses.

Adult↗