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PubMed2003

Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid.

Polymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real-time PCR method to resolve this problem, and we report herein a successful application of real-time PCR to diagnose invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in bronchial lavage fluid from an affected area to that from an unaffected area. This novel tool will provide rapid, sensitive, and specific diagnosis of pulmonary aspergillosis.

Adult↗
PubMed2006

Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis.

BACKGROUND: Caspofungin inhibits synthesis of beta-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS: The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS: Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSIONS: Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.

Adult↗
PubMed1992

Pulmonary aspergillosis: an unusual cytologic presentation.

Cytologic identification of Aspergillus is usually based on recognition of hyphal elements; conidia are rarely seen. We report a case of autopsy-proven pulmonary Aspergillosis which was studied antemortem by bronchoalveolar lavage. This mass arose in the clinical setting of chronic necrotizing pulmonary aspergillosis. The specimen contained numerous conidia, some of which exhibited germination. No hyphae were seen. This unusual cytologic expression of clinically significant fungal disease could be easily overlooked. Distinction of Aspergillus conidia from contaminating pollen is discussed.

Aspergillosis↗
PubMed1995

Detection of (1-3)-beta-D-glucan in a rat model of aspergillosis.

The G test containing factor G, fractioned from the Limulus lysate, was used to detect (1-3)-beta-D-glucan in a rat model of aspergillosis. Aspergillus fumigatus strain MF-13, 1 x 10(4) conidia, were inoculated transtracheally into rats treated with cortisone acetate (100 mg/kg) and fed a low-protein (8%) diet. Increased serum (1-3)-beta-D-glucan was found on the sixth day after inoculation in concentrations of 370 +/- 178 pg/ml (mean +/- SD) in untreated controls, and 154 +/- 43 pg/ml in rats treated with 0.5 mg/kg of amphotericin B. On day 11 (1-3)-beta-D-glucan concentrations were 2,590 +/- 2,940 pg/ml and 448 +/- 442 pg/ml, respectively. The elevation in levels of (1-3)-beta-D-glucan increased in correlation with the elevation of galactomannan antigen titers; (1-3)-beta-D-glucan is thus measurable during experimental aspergillosis in rats.

Amphotericin B↗
PubMed1988

Immunoblastic peripheral T-cell lymphoma confined to bone marrow in an infant presenting with aspergillosis.

A 16-month-old female infant presenting with pancytopenia and fever was found to have pulmonary aspergillosis and large-cell immunoblastic non-Hodgkin's lymphoma of peripheral post-thymic origin isolated to bone marrow. Extensive noninvasive evaluations failed to demonstrate the disease in other extramedullary sites. The malignant cells were large and polymorphous; lacked terminal transferase; expressed surface CD-2, CD-3, CD-8, and HLA-DR antigens, and showed rearrangements of the T-cell-receptor beta-chain gene. To our knowledge, this type of lymphoma in an infant has not been reported before. Furthermore, aspergillosis is a rare presenting feature in patients with lymphoproliferative disease. In our case, it may reflect an underlying immune deficiency associated with the transformation and proliferation of a suppressor T cell.

Aspergillosis↗
PubMed1993

Isolated primary cutaneous aspergillosis of the labia.

Isolated cutaneous aspergillosis is a rare complication of severe immunocompromised states. We describe a case of isolated cutaneous aspergillosis of the labia minora in an adolescent undergoing treatment for relapsed acute non-lymphocytic leukemia. The patient was successfully treated with a regimen that consisted of amphotericin B, granulocyte-colony stimulating factor, and surgical debridement.

Adolescent↗
PubMed1993

Unusual form of endobronchial Aspergillosis in a patient with cystic fibrosis.

The isolation of Aspergillus fumigatus from airway secretions from patients with cystic fibrosis (CF) is common and usually denotes asymptomatic colonization or allergic broncho-pulmonary aspergillosis (ABPA). A 12-year-old boy with CF acutely developed moderately severe symptoms of unremitting cough, fever, dyspnea, weight loss, and cyanosis. Chest radiographs demonstrated widespread unilateral infiltrates and volume loss. By bronchoscopy tenacious mucous plugs were seen occluding the left lower lobe bronchus. Cultures from sputum and sequential bronchoalveolar lavage grew Aspergillus fumigatus, but other significant criteria for diagnosing ABPA were lacking. No improvement was seen with a 3 week course of systemic corticosteroid and antibiotic therapy. Treatment with amphotericin B and short-term mechanical ventilation resulted in rapid resolution of all symptoms. This form of endobronchial aspergillosis has not been described previously.

Amphotericin B↗
PubMed1989

Aspergillosis of the sphenoid sinus simulating a pituitary tumor.

Sphenoidal aspergillosis is an unusual cause of sella turcica enlargement. Pituitary abscess secondary to Aspergillus had been reported. In the present case, a woman with sphenoid sinus aspergillosis mimicked a pituitary tumor. This patient survived her infection with intact pituitary function following a transsphenoidal approach. No postoperative amphotericine-B and 5-fluorocytosine were necessary. CT scan revealed a mass occupying the sphenoid sinus extending to the sella turcica. Factors that should alert the clinican to the presence of a sphenoidal and pituitary abscess in a patient with sella turcica enlargement are prior episodes of sinusitis, meningitis and immunosuppression and, as in the present case, hyperglycemia.

Aspergillosis↗
PubMed1978

Experimental mycosis in immunosuppressed rabbits. II. Acute and chronic aspergillosis.

The influence of immunosuppression on the course of experimental aspergillosis was investigated. Rabbits (2.2--2.5 kg) were divided into four groups. Group one received no drugs and was given 10(6) spores intravenously (IV) or intratracheally (IT) on two occasions one week apart. Weight gain or loss, appearance or disappearance of aspergillus antigen and/or antibody, and detection of aspergillosis at autopsy were followed. Group 2 received weekly injections of cyclophosphamide (70 mg/kg) starting two weeks prior and throughout the experiment. Animals in group three received either 1.14 or 2.25 mg/kg/day methyl prednisolone and group four received 2.28 mg/kg/day methyl prednisolone and 70 mg/kg/week cyclophosphamide. In group one, serum antigen levels were detected within a week of infection followed by antibody (I.D.) levels for three months. All animals grew normally and no infection was detected at autopsy. In group 2, animals survived one but not two challenges and had Ag but no Ab. In group 3, animals survived two challenges at the lower drug level but not the higher. All animals in group 4 succumbed to one challenge.

Acute Disease↗
PubMed1992

Aspergillosis of the paranasal sinuses.

The CT appearances of 13 cases of pathologically proven aspergillosis involving paranasal sinuses were reviewed. Symptoms included rhinorrhea, nasal obstruction, headache, facial pain and foul smell from the nose. At operation, these lesions appeared yellowish, brownish, grey or black in colour, and contained dirty or muddy material. Microscopic examination of the tissue removed showed an Aspergillus ball with chronic inflammation but without invasion of the nasal or sinus mucosa in 6 cases, and tissue invasion with necrosis and inflammation in 7. The structures involved, in order of frequency, were: maxillary sinus, nasal cavity, ethmoid sinus, orbit and cavernous sinus. The orbit was involved in 2 cases, therefore categorized as invasive; the other 11 cases were non-invasive as judged by CT. Calcification was seen in the lesions of 9 cases. In most cases the adjacent bony structures showed areas of erosion and sclerosis. Aspergillosis should be suspected in the presence of a mass in the paranasal sinuses or nasal cavity with calcification within it, which may not appear solid or dense and is separate from the walls of the sinus.

Aged↗
PubMed1980

Sero-diagnosis of invasive aspergillosis: attempts to determine antigen and antibody relevance to infection.

Attempt was made to define antigens and antisera which might prove useful in diagnosis of invasive aspergillosis in man. A convalescent antiserum (serum from rabbits after liver infection with Aspergillus fumigatus conidia) which might be more representative of immunological reaction to fungal growth in vivo, did not react in enzyme-linked immunosorbent assay with commerical antigens which are used at present in attempts to detect antibody response in systemic infections in man. However, this convalescent antiserum reacted with antigens from a range of fungal extracts. Antigens from young culture filtrates in particular the 24th culture filtrate are advocated as the standard antigens for antibody detection using conventional immunoprecipitation techniques. For the detection of circulating antigens, the use of convalescent antiserum in enzyme-linked immunosorbent assay might be promising in the early diagnosis of invasive aspergillosis.

Antibodies, Fungal↗
PubMedDate not supplied

Characterization of amphotericin B aerosols for inhalation treatment of pulmonary aspergillosis.

In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or organ transplantation. For prophylaxis against Aspergillus infections, amphotericin B may be a useful drug when inhaled as aerosol. In this study, the aerosolization of amphotericin B was investigated using eight different medical nebulizers under various operating conditions and with different amphotericin B concentrations in the solution. The output of each nebulizer was characterized by the mass flow of spray (drug) leaving the mouthpiece and by the size distribution of the droplets. An effective prevention of pulmonary aspergillosis via amphotericin B inhalation requires a high pulmonary deposition of the drug within an acceptable time of administration associated with a low deposition in the oropharyngeal region. To evaluate the dosages of drug delivered by various types of nebulizers to different regions of the respiratory tract, a semi-empirical deposition model was applied which is based on experimental aerosol deposition data from over 20 normal adults. The main results of the study are: Solutions with amphotericin B concentrations up to 10 mg/ml can be converted into sprays by means of medical nebulizers without any problems. For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the production of the aerosol. To optimize amphotericin B treatment of the lungs via inhalation, sprays with mass flows above 100 mg/min and with mass median aerodynamic diameters (MMAD) below 3 microns should be slowly inhaled by the subject. Applying these criteria to the nebulizers investigated, three out of eight devices have proved suitable for amphotericin B treatment via inhalation.

Administration, Inhalation↗
PubMed1997

Tolerance and efficacy of Amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients.

The tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily (t.i.d.), but only 20 (48%) patients managed to complete the scheduled regimen. One patient tolerated the full dose initially, but had to discontinue treatment when dyspnea developed as a result of pneumonia and acute respiratory distress. Another 22 patients (52%) experienced side effects, including eight (19%) who reported mild coughing and dyspnea but who tolerated the full dose and three (7%) patients whose dose was reduced to 5 mg t.i.d. Another six (14%) patients could tolerate only 5 mg t.i.d., and five (12%) others stopped treatment because of intolerance. Elderly patients (p < 0.05) and those with a history of chronic pulmonary obstructive disease (p = 0.09) were more likely to develop side effects during inhalation. Twelve (28%) patients developed proven of possible invasive fungal infections, but no correlation was established between infection and the total amount of amphotericin B inhaled. Inhalation of aerosolised amphotericin B is poorly tolerated and does not appear useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients.

Administration, Inhalation↗
PubMedDate not supplied

Pneumopericardium complicating invasive pulmonary aspergillosis: case report and review.

Pneumopericardium, the presence of air in the pericardial space, is a rare disorder that is usually caused by trauma. We describe a patient given induction chemotherapy for acute myelogenous leukemia who developed pulmonary aspergillosis that resulted in pericarditis and pneumopericardium. He responded to antifungal treatment and recovered from granulocytopenia, but died early during the next course of chemotherapy. Two other reported cases of pneumopericardium associated with pulmonary aspergillosis are summarized.

Adult↗
PubMedDate not supplied

Syndrome of the anterior spinal artery as the primary manifestation of aspergillosis.

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly occurring in immunocompromised patients. Beside cerebral involvement spinal cord lesions are extremely rare. To our knowledge, aspergillosis initially presenting with acute paraplegia due to mycotic thrombosis of the anterior spinal artery in a formerly healthy patient has, so far, not been reported. Neither a primary focus nor an underlying disease had been detected.

Acute Disease↗
PubMed1990

Inactivity of terbinafine in a rat model of pulmonary aspergillosis.

In a model of bronchopulmonary aspergillosis terbinafine did not improve survival of experimental animals in doses up to 80 mg/kg/day despite adequate lung concentrations. Pretreatment and aerosolization of the compound were also ineffective. Terbinafine was markedly less active in vitro when serum was used instead of Yeast-Nitrogen-Glucose-broth. It is concluded that a lack of bioavailability in the presence of serum may explain the lack of activity of terbinafine in experimental aspergillosis.

Aerosols↗
PubMed1994

Retrospective evaluation of a latex agglutination test for diagnosis of invasive aspergillosis in immunocompromised patients.

A commercial latex agglutination (LA) test for the detection of circulating Aspergillus galactomannan was evaluated in sera obtained from 121 immunocompromised patients, including 19 with proven invasive pulmonary aspergillosis. Patient urine (the specimen of choice for detection of galactomannan) was not tested with the LA test as 34 of 81 specimens from controls gave false-positive results. The sensitivity (95%), specificity (90%) and negative predictive value (99%) of the LA test were similar to previously published results obtained with two EIAs. However, the positive predictive value was only 67% compared to > or = 95% obtained with the EIAs. In addition, the LA test was also of less value than the EIAs in predicting the onset of invasive pulmonary aspergillosis. It was the earliest indicator of infection in only 1 of 19 proven cases.

Antigens, Fungal↗
PubMed1993

Aspergillosis in children with acquired immune deficiency.

Two children are presented with AIDS and aspergillosis. One child had pulmonary involvement while the other had invasion of the skull and brain. The rarity of aspergillosis in AIDS patients is discussed as well.

AIDS-Related Opportunistic Infections↗