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PubMed1978

Allergic bronchopulmonary aspergillosis caused by Aspergillus ochraceus.

A case with the characteristics of allergic bronchopulmonary aspergillosis is described. The species of Aspergillus involved, A. ochraceus, has not previously been found in this disorder. The organism had antigenic properties distinct from five other species of Aspergillus most commonly associated with allergic bronchopulmonary aspergillosis. The patient had immediate skin test, immunodiffusion, and radioallergosorbent reactivity to the species. Four per cent of 112 serum samples from others suspected of having allergic bronchopulmonary aspergillosis had precipitins to A. ochraceus only. It may be necessary in some cases to prepare and test extracts of the patient's Aspergillus isolate in order to confirm the diagnosis.

Adult↗
PubMed1992

Aspergillosis of the prostate associated with an indwelling bladder catheter: case report and review.

Fungal prostatitis is an uncommon disease whose presentation is usually similar to that of benign prostatic hypertrophy and is usually diagnosed unexpectedly after surgery for relief of prostatic obstruction. To our knowledge, we report the first case of prostatic aspergillosis that developed as a complication of indwelling bladder catheterization. This unusual manifestation of invasive aspergillosis occurred in a patient at risk for invasive fungal disease because of chronic corticosteroid use and recent administration of broad-spectrum antibiotics. The previously reported cases of prostatic aspergillosis are reviewed.

Aspergillosis↗
PubMed1985

The diagnosis of invasive aspergillosis by an enzyme-linked immunosorbent assay for circulating antigen.

An inhibition enzyme-linked immunosorbent assay (ELISA) capable of detecting 10 ng of aspergillus carbohydrate antigen/ml of serum was developed. When retrospectively applied to the sera of 19 patients with invasive aspergillosis, the ELISA detected antigen in 11 patients. None of 14 healthy controls or 28 patients with a variety of other infections were positive for circulating antigen. A rabbit model of invasive aspergillosis was also developed. Daily fungal cultures of blood were negative in the rabbits, as in human disease, but antigen was detected in increasing amounts up to the time of death. This ELISA is a sensitive, specific, and easily performed assay for circulating aspergillus antigen that should facilitate early diagnosis of invasive aspergillosis, heretofore, seldom made without invasive tests.

Adolescent↗
PubMed1987

Galactomannan antigenemia and antigenuria in aspergillosis: studies in patients and experimentally infected rabbits.

Purified galactomannan (GM) from Aspergillus fumigatus was used in both a radioimmunoassay and an enzyme-linked immunoassay for antigen detection. Results of the two tests seemed interchangeable. By one or both assays, GM was detected in serum from four of 12 rabbits lethally infected with A. fumigatus in concentrations ranging from 108 to 356 ng/ml. Serum antigen was detected in only two of 12 patients with invasive aspergillosis. Results of assay for GM in urine were far more encouraging. Urinary GM was detectable throughout the course of lethal aspergillosis in all 16 rabbits, in concentrations of 24-1,900 ng/ml. Urine from seven of 13 patients with invasive aspergillosis had GM concentrations of 1-83 ng/ml. Antigen excretion roughly paralleled extent of disease.

Animals↗
PubMed1991

The role of fluconazole in the early treatment and prophylaxis of experimental invasive aspergillosis.

The efficacy of fluconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with fluconazole at 60 or 120 mg/kg/day was begun 24 h after lethal challenge and compared to that with amphotericin B at 1.5 mg/kg/day. Fluconazole reduced mortality compared with that in untreated controls and at 120 mg/kg/day reduced the tissue burden of A. fumigatus 10- to 100-fold in liver, kidney, and lung. However, amphotericin B was more effective in sterilizing tissues. Both fluconazole and amphotericin B dramatically decreased or eliminated circulating aspergillus antigen. Prophylaxis with fluconazole, begun 48 h before sublethal challenge, sterilized liver and kidney tissues and significantly reduced the tissue burden in lung. Early treatment with fluconazole reduced mortality and reduced antigenemia but did not sterilize tissues. Fluconazole prophylaxis at these doses prevented dissemination of invasive aspergillosis. Fluconazole was shown to have activity in the early treatment and prophylaxis of experimental invasive aspergillosis.

Animals↗
PubMed1991

Endemic and epidemic aspergillosis associated with in-hospital replication of Aspergillus organisms.

When a new hospital opened in 1983, environmental culturing for Aspergillus organisms and surveillance for nosocomial aspergillosis cases were begun to characterize the relationship between environmental contamination and infection. Monthly air sampling demonstrated increasing concentrations of Aspergillus flavus and Aspergillus fumigatus to mean levels greater than 1 cfu/m3 during 1986-1987, accompanied by a progressive increase in incidence of aspergillosis to 1.2% in immunocompromised patients. This prompted an inspection that revealed heavy growth of Aspergillus organisms on air filters. Subsequent inspections of hospital wards showed small foci of A. flavus growth on other materials. Removal of the contaminated filters and improved environmental maintenance were associated with reduction in A. flavus and A. fumigatus to 0.01 cfu/m3 and a fourfold decline in aspergillosis incidence during the next 2 years. These findings, together with laboratory studies that showed aspergilli could proliferate on common hospital materials when moistened, indicate a need for careful environmental maintenance.

Air Microbiology↗
PubMed1992

Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation.

From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored.

Adult↗
PubMed1993

Combination therapy in experimental invasive aspergillosis.

Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A. fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.

Amphotericin B↗
PubMed1994

Efficacy of unilamellar liposomal amphotericin B in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: the potential role of bronchoalveolar D-mannitol and serum galactomannan as markers of infection.

A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. D-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, D-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits.

Agranulocytosis↗
PubMed1994

Chemoprophylaxis of invasive pulmonary aspergillosis.

Invasive aspergillosis in now the second most common mycosis encountered in patients with cancer, particularly those with haematological malignancies. The present review discusses strategies for the chemoprophylaxis of invasive pulmonary aspergillosis. Recommendations for chemoprophylaxis are currently based on the particular fungal pathogens seen in individual centres and the resources available. In many units, only BMT recipients are nursed in protected environments and the majority of patients at risk of invasive mycosis, i.e. patients undergoing remission induction or consolidation therapy, are nursed on open wards. The studies so far reported have included relatively small numbers of patients and provide insufficient data for definitive recommendations. The measures used at present should be considered as ad hoc approaches for use in units in which spore-free air for profoundly neutropenic patients is lacking. Nebulized amphotericin B allows deposition of a chemical barrier throughout the airways. Intravenous low dose amphotericin B would be protective when invasion occurs and is clearly the chemoprophylaxis of choice in patients with an established diagnosis of previous invasive aspergillosis at any site. The role of surgery in removing a focus of infection before further chemotherapy, should not be overlooked. The potential role of cytokines in accelerating host defence recovery may in future also prove to be important in controlling invasive fungal infection.

Animals↗
PubMed2002

Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis.

Emergence of resistance to antifungal drugs during therapy for invasive aspergillosis has received scant attention. We recovered Aspergillus isolates from six patients with invasive aspergillosis, who were receiving amphotericin B before fungal isolation. Although isolates were susceptible to amphotericin B in vitro, none of the patients survived. The MIC of amphotericin B for isolates was similar to that for isolates from 35 patients with no prior exposure to amphotericin B. Laboratory attempts to produce amphotericin B resistance in Aspergillus were unsuccessful. These data indicate that emergence of resistance to amphotericin B is uncommon during therapy for invasive aspergillosis.

Amphotericin B↗
PubMed1982

Nosocomial aspergillosis: a retrospective review of airborne disease secondary to road construction and contaminated air conditioners.

A retrospective review of autopsy records was performed to evaluate a clustering of patients shown to have invasive pulmonary aspergillosis during the period July 1, 1978 through October 31, 1980 at Milwaukee County Medical Center, Milwaukee, Wisconsin. During this period, ten patients, all of whom were immunosuppressed by either hematologic malignancy (two), advanced age (one), or iatrogenically to prevent rejection of renal allografts (seven) were found to have invasive pulmonary aspergillosis. Prospective and retrospective evaluations of the hospital environment correlated the clustering of cases to recent road construction, and recovery of Aspergillus fumigatus and A. flavus from window air conditioners used in the renal transplantation ward suggested that some of the patients had acquired the infection nosocomially. A review of autopsy records during a seven-year period following the initiation of the renal transplant program but antedating road construction of any major consequence revealed no invasive aspergillosis among any patient autopsied.

Adult↗
PubMed1998

Necrotizing bronchial aspergillosis as a cause of hemoptysis in sarcoidosis.

The case history is presented of a patient with recurrent massive hemoptysis caused by necrotizing bronchial aspergillosis associated with sarcoidosis. The involved segments (right IX and X) were resected for treatment of the life-threatening hemoptysis. Histologic examination of the resected specimen confirmed the diagnosis. Necrotizing bronchial aspergillosis is a rare variant form of invasive pulmonary aspergillosis and has not been described previously as a cause of hemoptysis in sarcoidosis.

Aspergillosis↗
PubMedDate not supplied

Radiologic-pathologic correlation of the CT halo sign in invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis in the immunocompromised host is difficult to diagnose. Early therapy with amphotericin B improves survival. We correlated early pathologic findings with high-resolution CT of a fixed-inflated air-dried lung obtained from an autopsied patient with invasive pulmonary aspergillosis. Two distinct types of lesions were found radiologically. A large zone of air space consolidation was shown to be a confluent bronchopneumonia, and small halo-like lesions were shown to correspond to a central fungal nodule surrounded by a rim of coagulative necrosis. The halo lesion may represent an early specific sign by which invasive pulmonary aspergillosis can be diagnosed.

Aspergillosis↗
PubMedDate not supplied

Crescent sign in invasive pulmonary aspergillosis: frequency and related CT and clinical factors.

PURPOSE: The aim of our study was to evaluate the frequency of the crescent sign on follow-up radiographs in patients with invasive pulmonary aspergillosis, correlated with initial CT and clinical findings. METHOD: Retrospective analysis of serial chest radiographs was performed to see the frequency of the crescent sign in 21 consecutive patients with pathologically proved invasive pulmonary aspergillosis. The appearance of the crescent sign was correlated with the pattern of parenchymal lesions on initial CT scans, the presence and duration of neutropenia, and underlying diseases. RESULTS: The crescent sign was seen in 10 of 21 patients (48%) on follow-up radiographic examinations. It was seen in patients with initially large [consolidation or mass; 9/11 (82%) patients] rather than small [nodule(s); 1/10 (10%) patients] parenchymal lesions (p = 0.002) on CT. The sign appeared in 7 of 17 (41%) patients with neutropenia 1-10 days after recovery from neutropenia. It appeared in three of four patients (75%) without neutropenia 4--8 days after treatment with amphotericin B. The appearance was not related to the duration (32 days in patients with crescent sign and 17 days without sign) of the neutropenic period (p > 0.05). The sign was seen in 8 of 15 (53%) patients with acute myelogenous leukemia and 2 of 6 (33%) patients with other diseases (p > 0.05). CONCLUSION: The crescent sign appears in about half of patients with invasive pulmonary aspergillosis with recovery from neutropenia, especially when the initial lesion is a consolidation or mass on CT scans.

Adolescent↗
PubMedDate not supplied

Necrotizing Aspergillosis of large airways: CT findings in eight patients.

PURPOSE: The aim of this study was to evaluate the CT findings of pathologically proven necrotizing aspergillosis of the large airways (necrotizing Aspergillus bronchitis). METHOD: Medical records and imaging studies from two tertiary medical centers were reviewed for pathologically proven cases of necrotizing aspergillosis of the large airways. Fiberoptic bronchoscopic examination and CT scans of the chest were available in all cases. Two thoracic radiologists who were blinded to the clinical and pathologic data reviewed the thoracic CT scans retrospectively and reached a final decision. The CT images were evaluated for the presence, distribution, and extent of CT findings. RESULTS: The study included eight patients, seven men and one woman, ranging in age from 28 to 67 years (mean age 46 years). All patients had histopathologically proved necrotizing Aspergillus of the large airways and no other superimposed infections. Six patients had leukemia, one had chronic liver disease, and one had chronic obstructive lung disease. All patients had bronchial wall thickening and focal bronchial narrowing involving a lobar or segmental bronchus. The bronchial narrowing was irregular or nodular in seven patients and smooth in one. Atelectasis distal to a narrowed bronchus was present in five patients. CONCLUSION: The CT findings of necrotizing bronchial aspergillosis include bronchial wall thickening, which is often nodular, and narrowing of the bronchial lumen, which is often associated with distal atelectasis.

Adult↗
PubMed2002

Cerebellar aspergillosis: case report and literature review.

OBJECTIVE AND IMPORTANCE: An unusual, but not unique, case of cerebellar aspergillosis associated with autologous peripheral blood stem cell transplantation for breast cancer is presented. CLINICAL PRESENTATION: A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections. INTERVENTION: After removal of pus and the abscess wall, the patient received local application of amphotericin B (AmB). She received AmB 1 mg/kg/d for 3 months and itraconazole 100 mg/kg/d for 1 year. After 3 months of AmB treatment, magnetic resonance imaging revealed that disease had not recurred. CONCLUSION: In cases of central nervous system aspergillosis, to increase the therapeutic efficiency, AmB can also be applied to the abscess cavity. Computed tomographic and contrast-enhanced magnetic resonance imaging scans play an important role in establishing early diagnosis in high-risk, immunocompromised patients.

Amphotericin B↗
PubMed1996

Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis.

BACKGROUND: The delay between the onset of invasive aspergillosis and the start of antifungal therapy is crucial for the patient's recovery. Early diagnosis is difficult in cancer patients through lack of precocious specific signs. We have investigated the clinical usefulness of circulating Aspergillus antigen monitoring in pediatric hematology patients with a new sensitive sandwich enzyme-linked immunosorbent assay. METHODS: A prospective study was conducted by assessing circulating galactomannan levels in high risk patients. Thirty-seven patients studied during an 18-month period were evaluated twice weekly during neutropenic phases with the sandwich enzyme-linked immunosorbent assay for serum Aspergillus galactomannan. RESULTS: Twelve patients had one or more episodes of positive circulating galactomannan detection, 10 of whom developed presumptive invasive aspergillosis. The clinical and radiologic signs occurred at a mean of 13.4 days (range, 0 to 48) after circulating galactomannan detection and reversed in 6 patients treated with amphotericin B at the same time circulating galactomannan detection became negative. Reappearance of circulating galactomannan was observed during subsequent neutropenic periods in 3 patients. CONCLUSIONS: The detection of galactomannan at concentrations as low as 1 ng/ml can be useful for the early initiation of antifungal therapy and monitoring treatment in clinically documented lung aspergillosis. This technique coupled with chest computed tomography could help to restrict the need of invasive diagnostic procedures in fragile patients.

Adolescent↗