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PubMed2006

Invasive aspergillosis in the recipients of liver retransplantation.

Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.

Adolescent↗

PubMed2002

Invasive Aspergillosis in Italian AIDS patients.

BACKGROUND: We studied the prevalence, epidemiological features, symptoms, diagnosis, treatment and outcome of invasive aspergillosis in AIDS patients in Italy. PATIENTS AND METHODS: All patients affected by both aspergillosis and AIDS hospitalized between January 1986 and April 1997 (before highly-active antiretroviral therapy, HAART) in four Italian Department of Infectious Disease. Patients were included in the study only if culture, cytology or histology showed firm evidence of Aspergillus infection. Invasive aspergillosis was defined as the presence of characteristic, closely septate hyphae with repeated acute angle branching in either biopsy materials or percutaneous aspirates from tissues other than the lung. Hyphae were identified using hematoxylin-eosin and methenamine silver stain. RESULTS: During the study, 54 out of 2,614 patients admitted with AIDS showed aspergillosis (2.1%). The disease usually occurred in patients with < 50 CD4 cells/mm(3). Aspergillosis was associated with neutropenia and steroid treatment. Nonspecific symptoms were frequently encountered. Fever and cough were both present in > 70% of the cases of pulmonary aspergillosis. Biopsy specimens were analyzed for definitive diagnosis. Invasive aspergillosis is usually treated with amphotericin B, but in 90% of the cases this did not prevent death. CONCLUSION: In AIDS patients with neutropenia and long-term steroid therapy, it is important to consider invasive aspergillosis in the differential diagnosis of opportunistic infections.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis.

We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.

Adult↗

PubMed1997

[Significance of Aspergillus fumigatus rDNA detected by polymerase chain reaction in diagnosis of pulmonary aspergillosis].

We have studied the clinical significance of Aspergillus fumigatus rDNA detected by polymerase chain reaction (PCR) for diagnosing aspergillosis. For this purpose, a specific and sensitive PCR assay was developed to amplify the 26S rDNA/intergenic spacer region of A. fumigatus. Control experiments showed that the set of primers used was capable of amplifying A. fumigatus DNA specifically and that the DNA amount of detection limit was 1 pg. Eighteen samples from 13 patients with aspergillosis and 36 samples from 24 patients without aspergillosis were tested by means of PCR, culture, latex agglutination test for galactomannan antigen and double gel diffusion assay for precipitation of antibodies to A. fumigatus. PCR showed positive test in 8 among 13 patients with pulmonary aspergillosis. On the other hand, culture of samples detected A. fumigatus in 6 patients. Galactomannan antigen and antibodies specific to A. fumigatus were positive in 2 and 6 patients respectively. These results indicated that PCR is the most sensitive among these 4 methods. Five patients showed negative PCR test despite of having pulmonary aspergillosis. Two of these patients were proved to have aspergillosis caused by A. flavus and A. niger. On the other hand, galactomannan antigen and A. fumigatus antibody were positive in one and 2 patients, respectively. PCR was positive in 2 out of 24 patients diagnosed as not having aspergillosis: one patient had diagnosis of acute bronchitis, but she showed positive culture of A. fumigatus. The other patient had diagnosis of lobar pneumonia, because any pathogens were not detected before PCR assay. The PCR assay we developed is a useful method for diagnosing aspergillosis caused by A. fumigatus as compared with other conventional methods.

Aspergillosis↗

PubMedDate not supplied

Invasive aspergillosis in critically ill patients: analysis of risk factors for acquisition and mortality.

OBJECTIVE: To investigate outcome in patients who develop invasive aspergillosis in the ICU, and to evaluate whether specific risk factors for the acquisition of invasive aspergillosis are associated with mortality. DESIGN: Retrospective cohort study (07/1997-12/1999) with screening of 8988 admissions. SETTING: 54-bed ICU of the 1060-bed Ghent University Hospital. PATIENTS: 38 ICU patients with invasive aspergillosis. Invasive aspergillosis was defined as proven by positive histology and tissue culture and as probable by a combination of clinical suspicion as well as microbiological and radiological data. Seventeen patients had risk factors (neutropenia, haematological malignancy, immunosuppressive therapy). In the other 21 apparently immunocompetent patients, invasive aspergillosis was a complication following ARDS, COPD, pneumonia, acute liver failure, burns, severe bacterial infection and malnutrition. MEASUREMENTS: Population characteristics and outcome were compared for patients with and without risk factors for the acquisition of invasive aspergillosis. RESULTS: Patients with risk factors had higher APACHE II scores. No difference was found between patients with and without risk factors in in-hospital mortality (82% vs. 71%; p=0.431). In patients with specific risk factors, the observed mortality was not different from the mortality as expected on basis of the APACHE II (p=0.940). In patients without risk factors the observed mortality exceeded the expected mortality (p<0.001). CONCLUSION: The incidence of invasive aspergillosis in this series is 4/1000 admissions. No difference in mortality was found between patients with and without risk factors for the acquisition of invasive aspergillosis. Yet, the prognosis of the patients without risk factors seems to alter more seriously by the development of this infection.

APACHE↗

PubMed1984

Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia.

A case-control study of patients with acute leukemia was done to identify significant risk factors for invasive pulmonary aspergillosis by reviewing the medical histories of 15 cases of pathologically proven invasive pulmonary aspergillosis and 45 controls. A history of lung or sinus disease, smoking, and multiple recurrences of leukemia did not increase the risk of invasive pulmonary aspergillosis. Cases and controls received similar chemotherapeutic regimens, and exposure to aminoglycosides, carbenicillin, trimethoprim-sulfamethoxazole, or corticosteroids was not significantly associated with development of invasive pulmonary aspergillosis. Among the factors tested, only granulocytopenia was associated with development of invasive pulmonary aspergillosis. Early in the course of granulocytopenia, patients developed signs of invasive pulmonary aspergillosis at a rate of approximately 1% per day. As the duration of granulocytopenia increased, the rate increased, approximating 4.3% per day between the 24th and 36th days. Of the 13 patients remaining granulocytopenic at 28 days, 7 had developed signs of invasive pulmonary aspergillosis. For patients with acute leukemia, granulocytopenia persisting longer than three weeks is the major risk factor for developing invasive pulmonary aspergillosis.

Acute Disease↗

PubMed1979

Invasive aspergillosis in acute leukemia: correlation with nose cultures and antibiotic use.

Aspergillosis in cancer patients is a problem. Because not all patients can undergo invasive procedures, we sought other methods for diagnosis. We reviewed the data from all patients with acute nonlymphocytic leukemia treated at our center during a 3-year period. Of 125 patients, 18 had invasive aspergillosis (cases). Eleven patients had nose cultures growing Aspergillus flavus or A. fumigatus; 10 of these 11 had aspergillosis, whereas only eight of 114 without such nose cultures had invasive disease (P less than 0.000001). Thus, A. flavus on nose culture appears "predictive" for aspergillosis. Absence of such a culture does not preclude infection. Of 125 patients, 61 had sterile nose culture(s) and 14 of the 18 cases had such a sterile nose culture. Only four of the 64 patients without sterile nose cultures developed aspergillosis (P less than 0.008), suggesting a relation between sterile nose culture and aspergillosis. Carbenicillin was used for a longer period among cases and patients with predictive nose cultures than among patients without aspergillosis. These data may help identify patients at risk of aspergillosis and help determine antifungal therapy when invasive procedures are contraindicated.

Acute Disease↗

PubMed2001

[A case of non-invasive pulmonary aspergillosis that rapidly deteriorated].

The pulmonary diseases caused by the Aspergillus species include invasive forms, for example, invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and non-invasive pulmonary aspergillosis. Though these forms are defined pathologically by the presence of the Aspergillus species that invades the lung tissue, they are used as clinical entities. We report a case of non-invasive pulmonary aspergillosis which, from the clinical data, appeared likely to be misdiagnosed as the chronic invasive form. A 45 year-old man received chemoradiotherapy for lung cancer as well as undergoing an left upper lobectomy. Two weeks after the surgery the patient developed a cough, high fever and chest pain. Chest radiography and chest computed tomography showed a rapidly enlarging cavity with an internal mass and infiltration in the left lower lung field. A transbronchial biopsy specimen of the cavity wall showed fungal hyphae. Bronchial washing culture grew Aspergillus fumigatus. Itraconazole and amphotericin B were administered, but the patient's condition did not improve. A left lower lobectomy was performed. The histologic findings showed that the fungal hyphae were only on the surface of the cavity wall, and were surrounded by necrosis and widespread inflammatory cell infiltration. No fungal invasion of the viable lung tissue was seen. The area of infiltration revealed an organizing pneumonia without Aspergillus or other organisms. Our final diagnosis was non-invasive pulmonary aspergillosis. There has been no recurrence of the lung cancer or of the pulmonary aspergillosis in the three years since surgery. It is reported that non-invasive pulmonary aspergillosis passes through a period so active that it seems to be the invasive form for its entire clinical course. To avoid confusion in diagnosis, establishment of a comprehensive clinical classification of pulmonary aspergillosis will be needed.

Aspergillosis↗

PubMed2002

[Multivisceral infarcts are complication of invasive aspergillosis].

Aspergillus fumigatus is one of the species of Aspergillus that causes aspergillosis. The clinical picture of invasive-disseminated aspergillosis is generally characterized by fever and respiratory distress that usually follows a fatal course. This form of intensive aspergillosis is suffered by severely immunossuppressed patients. There is another clinical form of severe aspergillosis, aortic aspergillosis, that appears after cardiac surgery. We present two cases of invasive aspergillosis complicated by multiple visceral infarcts involving the liver, spleen, kidneys, pancreas, thiroid and brain. Infarcts were confirmed in necropsy and appeared to be caused by an overwhelming amount of intravascular hiphae, which were observed in the infarcted areas acting forming septic embolus. We believe that multi-visceral infarcts are an underestimated complication of invasive aspergillosis. Given the progressive increase in the population of immunossuppressed patients, clinicians have to aware of all the possible presentations of invasive aspergillosis.

Aged↗

PubMed1993

An emerging opportunistic infection in HIV patients: a retrospective analysis of 11 cases of pulmonary aspergillosis.

Invasive pulmonary aspergillosis usually occurs in patients with severe granulocytopenia or defects of cell-mediated immunity secondary to cytotoxic chemotherapy or high-dose corticosteroids, but it is an unusual opportunistic infection in patients with AIDS. Eleven cases of Aspergillus pulmonary disease were diagnosed in HIV-infected patients from January 1985 to December 1992, in the Department of Infectious Diseases of the Catholic University. Four patients had invasive pulmonary aspergillosis, six probable pulmonary invasive aspergillosis and one allergic bronchopulmonary aspergillosis. Fiberoptic bronchoscopy with bronchoalveolar lavage was confirmed to be an useful tool for the diagnosis of pulmonary aspergillosis in AIDS patients. The response of aspergillosis to therapy, either amphotericin B or itraconazole, has usually been poor. It is possible to speculate that the longer survival of AIDS patients and the latter development of other functional immunological abnormalities related to HIV infection may allow the appearance of opportunistic infection, such as pulmonary aspergillosis, different from those more often observed.

AIDS-Related Opportunistic Infections↗

PubMed2000

Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies.

INTRODUCTION: The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA. MATERIALS AND METHODS: We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations. RESULTS: Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0. CONCLUSIONS: Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.

Adolescent↗

PubMed2001

Pulmonary aspergillosis: clinical presentation, diagnosis and therapy.

Pulmonary aspergillosis is a serious threat to those immunocompromised as a result of disease or therapy, and has been identified as a major cause of morbidity and mortality in asthmatic and cystic fibrosis patients. Pulmonary aspergillosis can occur in three principal forms: saprophytic, allergic and invasive. Saprophytic aspergillosis involves colonisation of the airways, without invasion or damage of viable tissue, and may present as an aspergilloma (fungus ball) consisting of a tangled mass of mycelium, fibrin, inflammatory cells and epithelial-cell debris. Necrotic tissue also may be invaded but usually only in those severely immunocompromised. Allergic aspergillosis is referred to frequently as allergic bronchopulmonary aspergillosis (ABPA), and may occur in approximately 25% of asthmatic and 10% of cystic fibrosis patients. ABPA presents as a non-infectious, potentially fatal inflammatory disease where antigens released by the fungal mycelium provoke an immune response. Invasive aspergillosis is probably the most serious form of the disease and involves the invasion of viable tissue. It occurs predominantly in patients with pre-existing lung damage, and can spread to other organs and distant sites in the body. Aspergillomas may be detected on chest X-ray as spherical-shaped objects, whilst allergic aspergillosis may be visualised by radiological techniques and computed tomography (CT) scan. Surgery may be employed in the case of aspergilloma, and chemotherapy relies upon the use of amphotericin B (liposomal and aerosolised) and itraconazole.

Aspergillosis↗

PubMed1997

[Pathology of bronchopulmonary aspergillosis].

This paper concerns the morphology of 3 types of bronchopulmonary aspergillosis: saprophytic aspergillosis (SPA), invasive aspergillosis (IVA) and allergic bronchopulmonary aspergillosis (ABPA)/allergic bronchopulmonary mycosis (ABPM). To know whether Aspergillus (ASP) in SPA only colonizes in preexisting cavities or presents significant pathogenecity, we examined 38 surgical specimens of SPA and 10 post-tuberculous open cavities (PT-OC). Macroscopically, SPA cavities had macroscopic ulcers (81.6%) and bronchi originating from the cavities (68.4%), in contrary to PT-OC that had neither of them. Microscopically, SPA cavities showed shallow ulcers (100%), coagulation necrosis (42.1%) and granulomatous reaction (52.6%), although ASP invasion to the viable lung tissue couldn't be discovered. The lung tissue around the SPA cavities showed various inflammation caused by transbronchial ASP dissemination from the cavities. We concluded that (1) SPA should be considered chronic destructive infection by ASP, but not colonization, (2) SPA couldn't be differentiated in quality from semi-invasive/chronic necrotizing pulmonary aspergillosis, and both should be categorized into secondary bronchopulmonary aspergillosis. Respecting IVA, we investigated 10 autopsy cases. In those cases, the disease was brought about in the lungs having no preexisting lesions. Three forms were distinguished; (1) 5 cases in that coagulation necrosis was a main feature (CN-IVA). (2) 2 cases having lung balls in cavitary lesions (LB-IVA), and (3) 3 cases showing suppurative lesions (SP-IVA). In CN-IVA and LB-IVA cases, ASP invaded to the viable lung tissue. But in 2 cases of SP-IVA, fungal hyphae were identified only in necrotic lesions but not in the viable tissue. Because the "invasive" was vague in definition, we should categorized these cases into primary bronchopulmonary aspergillosis. To determine the primary lesion of ABPA/ABPM, 5 lobectomy specimen were examined. All cases had hard or firm mucous plugs in the proximal bronchi, peripheral to which we found inflammation with tissue eosinophilia (bronchocentric granulomatosis with tissue eosinophilia : 5 cases, xanthogranuloma-like lesions : 2 cases, eosinophilic pneumonia : 2 cases and organizing pneumonia : 4 cases). Conglomerates of degenerated eosinophils, sometimes showing fir-structure, and fungal hyphae were recognized in both of mucous plugs and the peripheral lesions. We concluded that the mucous plug was the primary lesion of ABPA/ABPM.

Aged↗

PubMed1996

Radiodense concretions in maxillary sinus aspergillosis: pathogenesis and the role of CT densitometry.

The purpose of this study was to investigate by CT the origin of radiodense maxillary sinus concretions and whether CT densitometry is effective in the prediction of maxillary sinus aspergillosis and in the differentiation of the origin of these concretions. In a prospective study in 21 patients with radiodense maxillary sinus concretions detected by radiography, a preoperative CT study of the paranasal sinuses and the concretions was undertaken. Additional scans of the upper alveolar ridge were also performed. Radiological findings were compared with clinical symptoms and with CT findings, especially CT densitometry of the sinus concretions and dental root-filling material. All patients underwent a functional Caldwell-Luc operation; histological and microbiological examinations were performed. Fifteen of the 21 patients (71.4%) with radiodense concretions had a histological and microbiological diagnosis of sinus aspergillosis. The sinus concretions had CT densities higher than 2000 HU (Hounsfield units) in 15 patients and lower than 2000 HU in 6. fourteen of 15 patients (93.3%) with concretions having CT densities higher than 2000 HU had a postoperative diagnosis of maxillary sinus aspergillosis. The mean CT density of the sinus concretions in patients with maxillary sinus aspergillosis was 2868 HU (range 1870-3070 HU), and in patients without aspergillosis was 778 HU (range 228-2644 HU). The mean CT density of the dental root-filling material was 2866 HU (range 2156-3070 HU). Paranasal sinus CT with CT densitometry of a sinus concretion has a higher accuracy than standard radiography and clinical findings in the prediction of maxillary sinus aspergillosis (93.3% vs 71.4%). CT densitometry helps to confirm the dental origin of maxillary sinus concretions and to explain a possible dental pathogenesis of maxillary sinus aspergillosis.

Adult↗

PubMed1999

A four-year review of fatal Aspergillosis.

To investigate the incidence, underlying diseases, and macropathological and microbiological features of invasive aspergillosis in a university hospital, the protocols of 1187 autopsies performed during the 4-year period 1993-1996 were reviewed. Invasive aspergillosis was diagnosed as the cause of death in 48 (4%) cases, four (8%) of which did not involve severe primary immunosuppression. In seven (15%) cases no pulmonary involvement was found; in six of these cases the portal of infection could not be established, whereas in one case invasive aspergillosis originated from Aspergillus peritonitis. Aspergillus grew in 42% of the samples obtained from the respiratory tracts of 32 patients with pulmonary aspergillosis and submitted within 10 days antemortem; at least one positive culture was obtained from 20 (63%) of these patients. It is concluded that the diagnosis of aspergillosis by means of culture has an appreciable sensitivity. Fatal invasive aspergillosis was rare among patients without severe immunosuppression, whereas invasive aspergillosis without pulmonary involvement was unexpectedly frequent.

Adult↗

PubMed1984

Role of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia.

The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia have not been examined. The results of 21 bronchoscopic procedures in 19 patients with invasive pulmonary aspergillosis and acute leukemia were reviewed. Analysis was confined to the 16 patients who had histopathologically documented infection on biopsy or at autopsy. Fiberoptic bronchoscopy established or suggested the diagnosis of invasive pulmonary aspergillosis in eight of 16 (50 percent) patients. Transbronchial or bronchial biopsy added only one diagnosis to those obtained by bronchial washing and brushing. Although fiberoptic bronchoscopy was a safe and well-tolerated procedure in our patients with invasive pulmonary aspergillosis and acute leukemia, its success rate was only 50 percent overall, and it appeared to be even less successful when performed early in the course of the disease. Fiberoptic bronchoscopy is a useful first procedure for the evaluation of patients with acute leukemia and possible invasive pulmonary aspergillosis, but a negative result does not exclude aspergillosis. Further diagnostic procedures, including repeated bronchoscopy, or institution of empiric antifungal therapy may be warranted if the clinical suspicion of invasive pulmonary aspergillosis is high.

Acute Disease↗

PubMed1985

Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia.

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.

Acute Disease↗

PubMed1994

NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.

BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal. METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure. RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed. CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.

AIDS-Related Opportunistic Infections↗