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Use of amphotericin B aerosols for the prevention of pulmonary aspergillosis.

Invasive pulmonary Aspergillus infections are increasingly recognized among severely neutropenic and/or immunosuppressed individuals. As the infections are usually acquired through the inhalation of Aspergillus conidia, at present prevention of invasive pulmonary aspergillosis consists mainly of the reduction of environmental exposure to aspergillus conidia. More recently, prophylaxis with amphotericin B aerosols has been investigated. Inhalations with amphotericin B aerosols significantly delayed mortality in an animal model of invasive pulmonary aspergillosis and high pulmonary concentrations of amphotericin B could be achieved. In man, pulmonary deposition of amphotericin B could also be demonstrated using commercially available nebulizers. Inhalations were well tolerated with little systemic absorption of the drug. In order to evaluate the efficacy of aerosol amphotericin B administrations for the prevention of invasive pulmonary aspergillosis, a prospective randomized trial has been initiated.

Aerosols↗

Primary lymph node invasive aspergillosis.

A case of apparently primary lymph node granulomatous aspergillosis is described. A review of the so-called primary aspergillosis cases since 1977 shows that granulomatous instead of exudative inflammation patterns have been observed in histological sections only when neither major nor minor predisposing factors have been detected in the clinical history of the patients. A possible pathogenetic role of selectively impaired cell-mediated immune response in these cases is hypothesized. Flucytosine treatment is indicated in a few selected cases of deep aspergillosis.

Adolescent↗

Oral itraconazole plus nasal amphotericin B for prophylaxis of invasive aspergillosis in patients with hematological malignancies.

The use of oral itraconazole (200 mg daily) plus nasal amphotericin B (10 mg daily) for prophylaxis of invasive aspergillosis was evaluated in 164 patients with hematological malignancies at risk due to presence of neutropenia and/or steroid therapy. This prophylactic regimen was evaluated for a period of two years. Two hundred and ninety patients with similar characteristics who were observed over the three-year period prior to the introduction of prophylaxis served as historical control group. Environmental surveillance during the study period showed constant contamination of the air with Aspergillus. Prophylaxis significantly reduced the incidence of proven invasive aspergillosis from 12/290 to 0/164 (p = 0.004), and reduced the mortality rate from 8/290 to 0/164. The incidence of proven plus probable aspergillosis amounted to 34/290 in the control group and 8/164 in the study group (p = 0.01); the mortality rates were 11/290 (3.7%) and 2/164 (1.2%) respectively. All nasal cultures in the study group were negative for Aspergillus. The prophylactic regimen was well tolerated. Larger studies assessing each agent alone and in combination are necessary to confirm these observations.

Administration, Intranasal↗

Catheter-related cutaneous aspergillosis complicated by fungemia and fatal pulmonary infection in an HIV-positive patient with acute lymphocytic leukemia.

A case of intravenous catheter-related cutaneous aspergillosis and Aspergillus fumigatus fungemia in an HIV-positive patient with Burkitt-cell acute lymphocytic leukemia is reported. The patient developed pulmonary aspergillosis with a rapidly fatal outcome despite recovery from neutropenia and improvement of the underlying malignancy. The unusual severity and rapid spread of the infection, despite normal neutrophil count and prompt antifungal therapy, suggest that HIV-related immunocompromise might play a role in the impairment of host defences against Aspergillus infection. Thus catheter-related cutaneous aspergillosis could lead to a severe deep-seated infection in HIV-positive patients.

Adult↗

Pulmonary aspergillosis due to Aspergillus terreus combined with staphylococcal pneumonia and hepatic candidiasis.

A female patient with systemic lupus erythematosus (SLE) developed pulmonary aspergillosis with staphylococcal pneumonia and hepatic candidiasis. Aspergillus terreus, which is a rare causative organism of pulmonary aspergillosis, was identified from a pulmonary lesion by culture. The aleurioconidium production, a characteristic of the genus Aspergillus sect. terrei, was demonstrated on short and irregular hyphal features in tissue sections. This report is the first of a combined case of pulmonary aspergillosis due to A. terreus with infections caused by other microorganisms.

Adult↗

Meningotheliomatous meningioma accompanied by aspergillosis at the skull base.

A 73-year-old man was admitted because of right frontal headache and gradual loss of right visual acuity, which had been occurring for 1 year. He had been treated with corticosteroids under the diagnosis of retrobulbar optic neuritis at a nearby clinic. Magnetic resonance imaging (MRI) revealed a nodular lesion at the tuberculum sellae, which showed isointensity on T1-weighted images, iso- to low-intensity on T2-weighted images, and heterogeneous enhancement with Gd-DTPA. Meningioma was diagnosed, and surgery was performed but was limited to biopsy because of intraoperative detection of purulent inflammation of the nodule. Histologic examination revealed aspergillosis in a portion of the meningotheliomatous meningioma. The patient died of meningoencephalitis about 1 month after surgery in spite of extensive treatment with antifungal agents. MRI findings of meningioma and aspergillosis are similar, thus making preoperative diagnosis difficult. However, this case provides evidence that aspergillosis should be included in the differential diagnosis when a skull-base meningioma-like nodule is noted if sinusitis is revealed in the sphenoid sinus.

Aged↗

[Localized invasive intracranial aspergillosis with multiple cranial nerve failure -- case report and review of the literature].

Contrary to the more frequent hematogenously spread cerebral aspergillosis, localized invasive intracranial aspergillosis is a fungal infection that can also occur in patients who are not severely immunosuppressed. This illness can be effectively treated in some of these patients by early and rigorous therapy. Localized invasion of the fungus, generally from one of the nasal sinuses, causes intracranial growth mainly along the base of the skull and larger vessels,where fibrous, granulomatous tissue develops. This generally leads to damage of the cranial nerves (primarily I-VI) as well as localized pain syndromes. We report on the clinical course documented by MRI of a patient with localized invasive intracranial aspergillosis who had multiple failure of cranial nerves following surgery for an aspergilloma of the maxillary sinus. Clinical course, imaging findings, and treatment of the illness are discussed with a review of the relevant literature.

Aged↗

Immunoparalysis as a cause for invasive aspergillosis?

Aspergillus infections are among the most feared opportunistic infections in humans. These organisms are ubiquitous in nature; protection against infection is usually provided by anatomical barriers and by the immune system. Tissue invasion by Aspergillus is uncommon, occurring primarily in the setting of immunosuppression. The prognosis of invasive aspergillosis is very poor. Although it is widely recognised that critically ill patients in the Intensive Care Unit (ICU) are at risk for nosocomial infections, it is not generally appreciated that such patients may also be at risk for opportunistic infections usually seen only in immunocompromised patients. This might be explained by a biphasic immunological pattern during sepsis: an early hyperinflammatory phase followed by an anti-inflammatory response, leading to a hypo-inflammatory state, the so-called compensatory anti-inflammatory response syndrome (CARS or immunoparalysis). We describe four patients admitted to our ICU for various reasons, without a history of abnormal immune function, who developed invasive pulmonary aspergillosis. We hypothesise that the occurrence of these opportunistic infections in our patients may have been due to immunoparalysis, and that perhaps all ICU patients with sepsis and multiple organ dysfunction syndrome (MODS) may be at risk for opportunistic infections such as aspergillosis as a result of this syndrome. Physicians treating critically ill patients in the ICU should be aware of the CARS/immunoparalysis syndrome and its potential to cause opportunistic infections, even in patients with normal immune function prior to ICU admission.

Aged↗

An unusual presentation of invasive aspergillosis after lung transplantation.

Aspergillus infections in lung transplant patients are frequently reported with a large pattern of manifestations varying from simple colonization of the lungs to complicated infections. Pulmonary invasive aspergillosis and disseminated aspergillosis often result in death. The majority of cases occur during the first months after transplantation with pulmonary involvement and have been described as the first clinical localization of the disease. Here we present the first reported case of an endophthalmitis caused by Aspergillus fumigatus developing 18 months after lung transplantation, and presenting as a manifestation of invasive aspergillosis.

Aspergillosis↗

Chronic systemic aspergillosis in a patient with acute myeloid leukemia.

Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis.

Adult↗

Percutaneous treatment with amphotericin B of mycotic lung lesions from invasive aspergillosis: results in 10 immunocompromised patients.

The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i.v. therapy; under CT guidance, a median of 10 cm3 per session of a 1 mg/cm3 diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences.

Amphotericin B↗

[Invasive aspergillosis of the orbit in immunocompetence].

BACKGROUND: An isolated aspergillosis of the sphenoidal sinus is a difficult diagnosis because the often misleading clinical symptoms of this rare disease can develop late and first be presented to the ophthalmologist. Because of this even life-threatening disease in normally immunodeficient patients, fast diagnostics and treatment is indicated. CASE REPORT: We report about an immunocompetent man to suffer from an invasive aspergillosis involving the sphenoidal sinus after external operation of a mucocele. Aspergillus infiltrated the right orbit by bone erosion and led to an acute loss of vision on his right eye and a pathological visual field (visual acuity 0.1). A systemical antimycotic therapy was performed and the right orbit and the optical channel were operated to remove the mycosis. During operation the optical nerve was found to be completely surrounded by the mycosis. After surgery visual acuity recovered slowly but completely in about two weeks (visual acuity 1.0) and visual field examination revealed normal findings. These findings were stable now for one year. CONCLUSION: The main findings of unilateral acute visual loss and pre-operations of the paranasal sinuses in combination with persistent headache can lead to the suspect of an aspergillosis infection. It is important to establish correct diagnosis--especially in immunocompetent patients--early to prevent a probably irreversible visual loss and in an advanced stage to handle the life-threatening risk of this disease.

Aged↗

Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient affected by Castleman disease.

One case of aspergillosis and mucormycosis occurring in a patient with stage-IV Castleman disease was investigated. The patient, who had undergone polychemotherapy and was in otherwise good general condition, without lymphadenopathies or imbalance of the immune system, presented with a palatal ulceration that progressively involved the palatal mucosa and bone, the paranasal sinuses and the orbit. Repeated cultural examinations were always negative. He had undergone multiple cytological smears of the inflammatory infiltration and biopsies of both the oral and nasal mucosa, which resulted in extensive necrotic debris and suppurative inflammation, and, on the very last biopsy, fungal hyphae, spores and conidia were also detected. These were large, branching, mostly non-septate hyphae, associated with conidiophores and conidia, the latter appearing dark brown to black in the histological preparations. Following the diagnosis of combined mucormycosis and aspergillosis, the patient underwent prolonged topic and systemic antibiotic treatment that resulted curative. Mucormycosis usually is a fatal complication of head and neck or systemic disorders, leading to severe immune suppression. Nevertheless, early diagnosis may be achieved using a combination of special stains and may lead to effective antibiotic treatment and cure of the patient, even if associated with other opportunistic infections, such as aspergillosis.

Aged↗

Aortic lesions in aspergillosis: histopathological study of two autopsy cases.

The involvement of the aorta in aspergillosis is relatively rare, and its histopathological features have not been described in detail. In two autopsy cases of invasive aspergillosis in immunologically compromised patients with hematological disorders, the aspergillotic lesions of the aorta showed different characteristic histopathological features depending on the three layers of aortic wall. Intimal lesions were formations of the mural thrombus composed of aggregates of numerous fungal hyphae arranged perpendicularly to the aortic wall. In the media, smooth muscle cells were completely necrotic (anemic infarct of the media), while the framework of elastic fibers was well preserved, with only a few fungal hyphae detected. In the adventitia, an intense, partly granulomatous chronic inflammatory change with fibrosis was observed in association with mycotic embolic occlusion of the vasa vasorum. These histopathological changes were considered to represent one of the typical tissue reaction patterns in the wall of an elastic artery in aspergillosis.

Aorta, Thoracic↗

CNS-manifestation of aspergillosis in an extremely low-birth-weight infant.

UNLABELLED: Invasive aspergillosis is a rare condition in term and preterm infants. We present here the fatal case of a 28-week gestational age preterm baby who developed pulmonary, hepatic and central nervous system aspergillosis during the first days of life. A hyperechogenic lesion adjacent to the lateral ventricle was diagnosed by ultrasound and initially considered to represent periventricular leukomalacia. Within several days the lesion increased in size and was then falsely considered to be an intraventricular haemorrhage. Aspergillus fumigatus was ultimately isolated in the tracheal aspirates, ascites and in material recovered by open brain biopsy. Despite treatment with conventional and liposomal amphotericin B the infant patient died. CONCLUSION: Invasive aspergillosis has to be considered in the differential diagnosis of an unusual hyperechogenic brain lesion in very low-birth-weight infants with persistent symptoms and signs of systemic infection despite broad-spectrum antibacterial therapy. Consideration of this diagnosis should result in an aggressive diagnostic work-up to allow early initiation of an appropriate treatment.

Antifungal Agents↗

Predictors of postoperative complications after radical resection for pulmonary aspergillosis.

OBJECTIVE: Although surgery has proven to be the best treatment for pulmonary aspergillosis, with the highest chance of achieving complete remission, it is difficult to determine the surgical indications for this disease because of the high incidence of postoperative complications. We conducted this study to identify some predictors of postoperative complications, in an attempt to reduce the morbidity rate. METHODS: We retrospectively analyzed the medical records of 31 patients (18 men, 13 women; median age 53 years) who underwent radical resection for pulmonary aspergillosis between 1976 and 2004. The clinical manifestations, surgical procedures, and postoperative complications were reviewed to clarify the predictors of postoperative complications. RESULTS: The morbidity rate associated with major complications such as intrapleural bleeding, bronchopleural fistula, and empyema, resulting in further surgery, was 19%. Univariate analysis revealed the predictors of major complications to be sex, severe preoperative symptoms, and extensive pulmonary resection. Multivariate analyses also indicated that preoperative symptom severity was an independent predictor of major complications. CONCLUSIONS: Pulmonary aspergillosis should be resected before the symptoms become too severe if the patient is a surgical candidate.

Adult↗

Late pleuropulmonary aspergillosis after the treatment of pneumothorax: report of three cases.

A bullectomy for spontaneous pneumothorax is often combined with pleurodesis to prevent recurrence. A recurrent or progressive residual bullous lung beneath adhesive pleura neovascularized from the chest wall may be affected by aspergillosis. Of the 12 patients with pulmonary aspergillosis secondary to bullous lung disease treated surgically at our hospital since 1974, 3 underwent a bullectomy with pleurodesis for spontaneous pneumothorax. The presenting symptoms in all cases were hemosputum. Aspergillus lesions affected the patients in the right upper lobe, the left apical segment, and both apical segments at 16, 9, and 13 years, respectively, after a bullectomy. Angiograms demonstrated hypervascularization in the intercostal and internal thoracic arteries, as well as in the bronchial branches. Catheter embolization for airway bleeding was not effective in 1 patient. Four operations, including an emergency procedure for massive intrapulmonary bleeding, were performed. These included a right upper lobectomy followed by a left upper segmentectomy at second-look operation in 1 patient who required bilateral chest wall resections. All patients survived the operations. Intraoperative bleeding ranged between 700 and 3 500 ml (1 543 ml on average), and bleeding foci were mainly from the chest wall, with hypervascularization stemming from the ipsilateral chest wall. Postoperative complications included pleural space hemorrhaging and a bronchopleural fistula, both of which required additional chest wall resections. Patients with bullous lung disease late after a bullectomy with pleurodesis may thus be associated with complex pleuropulmonary aspergillosis, which requires surgical therapy concomitant with a chest wall resection.

Adult↗

Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients by seminested PCR assay of tissue samples.

Aspergillosis and mucormycosis are the most common mold infections in patients with hematological malignancies. Infections caused by species of the genus Aspergillus and the order Mucorales require different antifungal treatments depending on the in vitro susceptibility of the causative strain. Cultures from biopsy specimens frequently do not grow fungal pathogens, even from histopathologically proven cases of invasive fungal infection. Two seminested PCR assays were evaluated by amplifying DNA of zygomycetes and Aspergillus spp. from organ biopsies of 21 immunocompromised patients. The PCR assays correctly identified five cases of invasive aspergillosis and six cases of mucormycosis. They showed evidence of double mold infection in two cases. Both assays were negative in five negative controls and in two patients with yeast infections. Sequencing of the PCR products was in accordance with culture results in all culture-positive cases. In six patients without positive cultures but with positive histopathology, sequencing suggested a causative organism. Detection of fungal DNA from biopsy specimens allows rapid identification of the causative organism of invasive aspergillosis and mucormycosis. The use of these PCR assays may allow guided antifungal treatment in patients with invasive mold infections.

Adult↗