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Itraconazole therapy in aspergillosis: study in 49 patients.

Itraconazole, 200 to 400 mg once daily, was administered to 49 patients with different types of aspergillosis: pulmonary aspergilloma (14 patients), chronic necrotizing pulmonary aspergillosis (14), and invasive aspergillosis (21). Itraconazole was prescribed alone or in combination or after treatment with amphotericin B and flucytosine. Of 14 aspergilloma patients, 2 were cured and 8 had symptomatic improvement. In chronic necrotizing pulmonary aspergillosis, 7 of 14 patients were cured and 6 improved significantly. In invasive aspergillosis treatment failed in 6 patients and 15 were cured. Itraconazole can be an alternative to amphotericin B in the treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis. In aspergilloma itraconazole may be useful in inoperable cases.

Adult↗

Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence.

Invasive aspergillosis is a rare disease in intensive care unit (ICU) patients and carries a poor prognosis. The aim of the present study was to determine the attributable mortality due to invasive aspergillosis in critically ill patients. In a retrospective, matched cohort study (July 1997-December 1999), 37 ICU patients with invasive aspergillosis were identified together with 74 control patients. Matching of control (1:2) patients was based on the acute physiology and chronic health evaluation (APACHE) II classification: an equal APACHE II score (+/-1 point) and diagnostic category. This matching procedure results in an equal expected in-hospital mortality for cases and controls. Additionally, control patients were required to have an ICU stay equivalent to or longer than the case before the first culture positive for Aspergillus spp. Patients with invasive aspergillosis were more likely to experience acute renal failure (43.2% versus 20.5%; P = 0.020). They also had a longer ICU stay (median: 13 days versus seven days; P < 0.001) as well as a more extended period of mechanical ventilator dependency (median: 13 days versus four days; P < 0.001). Hospital mortalities for cases and controls were 75.7% versus 56.8%, respectively (P=0.051). The attributable mortality was 18.9% (95% CI: 1.1-36.7). A multivariate survival analysis showed invasive aspergillosis [hazard ratio (HR): 1.9, 95% CI: 1.2-3.0; P = 0.004] and acute respiratory failure (HR: 6.5, 95%: 1.4-29.3; P < 0.016) to be independently associated with in-hospital mortality. In conclusion, it was found that invasive aspergillosis in ICU patients carries a significant attributable mortality of 18.9%. In a multivariate analysis, adjusting for other co-morbidity factors, invasive aspergillosis was recognized as an independent predictor of mortality.

Aspergillosis↗

Invasive aspergillosis in the immunocompromised host: utility of computed tomography and bronchoalveolar lavage.

OBJECTIVE: Bronchoalveolar lavage is performed almost routinely in immunocompromised patients with suspected pneumonia, but it has a low yield in the diagnosis of pulmonary aspergillosis. The aim of this study was to determine whether computed tomography (CT) is helpful in determining the likelihood of a positive bronchoalveolar lavage by allowing distinction of patients with angioinvasive aspergillosis from those with Aspergillus bronchopneumonia. METHODS AND RESULTS: A retrospective study was performed including consecutive immunocompromised patients with suspected pneumonia who underwent CT scanning of the chest and bronchoalveolar lavage and who had definite diagnosis of pulmonary aspergillosis. The CT scans were reviewed by two chest radiologists and classified as showing features consistent with angioinvasive or airway invasive aspergillosis. Twenty-one patients met the inclusion criteria. Bronchoalveolar lavage was positive for fungi in two of 11 patients with CT findings consistent with angioinvasive aspergillosis and eight of 10 patients with CT scans consistent with Aspergillus bronchopneumonia (P < 0.01, chi-squared test). CT findings of angioinvasive aspergillosis included nodules measuring 1-3.5 cm in diameter in six, segmental consolidation in three, and both nodules and segmental consolidation in two patients. CT findings of Aspergillus bronchopneumonia including peribronchial consolidation in five, small centrilobular micronodules in one, and both in four patients. CONCLUSIONS: Chest CT is helpful in determining the likelihood of successful diagnosis of pulmonary aspergillosis by bronchoalveolar lavage.

Adolescent↗

Changing role of invasive aspergillosis in AIDS--a case control study.

OBJECTIVE: From December 1993 until January 1996 we observed 10 cases of invasive aspergillosis in a cohort of 140 patients with AIDS (7%). By contrast, no invasive aspergillosis was diagnosed in a cohort of 278 patients with AIDS between 1986 until 1993. METHODS: Case controls were assigned randomly to each patient with invasive aspergillosis from the total pool of HIV-infected patients. Patients with invasive aspergillosis were studied retrospectively by matched-pairs analysis with respect to risk factors, radiological, microbiological and autopsy findings. RESULTS: Patients with aspergillosis had more AIDS-defining events (3.5 [2-5] vs. 2 [2-3], median [range], P < 0.05) and a longer median survival time with full-blown AIDS (31.5 [14-45] months vs. 20.5 [5-32] months, P < 0.005) than their case controls. Patients with invasive aspergillosis tended to have lower white blood cell counts and exhibited significantly decreased median CD4 counts (7 [0-44]/mm3 vs. 27 [8-57]/mm3, P < 0.05). CONCLUSIONS: Due to better management of opportunistic diseases and improved antiretroviral therapy, the lifespan of patients with full blown AIDS is prolonged. Patients who have survived four or more AIDS-defining events are at risk for invasive aspergillosis. This risk is associated with low white blood cell counts and CD4 cell counts.

AIDS-Related Opportunistic Infections↗

Central nervous system aspergillosis in allogeneic stem cell transplant recipients.

Invasive aspergillosis (IA) is relatively common in allogeneic stem cell transplant (SCT) recipients. Although lungs are the most common site, central nervous system (CNS) involvement is also observed in this setting. We have retrospectively studied 14 cases of CNS aspergillosis found in a cohort of 455 allogeneic SCT recipients (incidence 3%). All patients, except one, had experienced acute graft-versus-host disease treated with high-dose methylprednisolone, and eight patients (57%) had also received ATG. The median time to the diagnosis of CNS aspergillosis was 124 days (range 49-347 days) from SCT. Pulmonary aspergillosis had been diagnosed earlier in four patients (29%). The most common initial symptoms of CNS aspergillosis were convulsions, hemiparesis, and mental alteration. Neuroradiological studies revealed single (two patients) or multiple (seven patients) focal lesions of 0.2-9 cm in diameter. Despite clinical suspicion in many patients, a confirmed diagnosis of CNS aspergillosis was made during life in only one patient. A total of 12 patients (86%) received amphotericin B. Despite therapy, all patients died 0-27 days (median seven days) after the initial CNS symptoms. CNS aspergillosis is not uncommon in allogeneic SCT recipients. Clinical manifestations are usually dramatic and progress quickly. Earlier and more effective treatment of IA is needed to prevent dissemination of infection into the CNS.

Adolescent↗

Pulmonary aspergillosis in the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: Symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). We describe the predisposing factors, the clinical and radiologic features, and the therapeutic outcomes in 13 patients with pulmonary aspergillosis, all of whom had human immunodeficiency virus (HIV) infection and 12 of whom had AIDS. RESULTS: Pulmonary aspergillosis was detected a median of 25 months after the diagnosis of AIDS, usually following corticosteroid use, neutropenia, pneumonia due to other pathogens, marijuana smoking, or the use of broad-spectrum antibiotics. Two major patterns of disease were observed: invasive aspergillosis (in 10 patients) and obstructing bronchial aspergillosis (in 3). Cough and fever, the most common symptoms, tended to be insidious in onset in patients with invasive disease (median duration, 1.3 months before diagnosis). Breathlessness, cough, and chest pain predominated in the three patients with obstructing bronchial aspergillosis, who coughed up fungal casts. Radiologic patterns included upper-lobe cavitary disease (sometimes mistaken for tuberculosis), nodules, pleural-based lesions, and diffuse infiltrates, usually of the lower lobe. Transbronchial biopsies were usually negative, but positive cultures were obtained from bronchoalveolar-lavage fluid or percutaneous aspirates. Dissemination to other organs occurred in at least two patients, and direct invasion of extrapulmonary sites was seen in two others. The results of treatment with amphotericin B, itraconazole, or both were variable. Ten of the patients died a median of 3 months after the diagnosis (range, 0 to 12 months). CONCLUSIONS: Pulmonary aspergillosis is a possible late complication of AIDS; if diagnosed early, it may be treated successfully.

Acquired Immunodeficiency Syndrome↗

Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program.

The incidence of invasive aspergillosis was estimated among 4621 hematopoietic stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites dispersed throughout the United States, during a 22 month period from 1 March 2001 through 31 December 2002. Cases were identified using the consensus definitions for proven and probable infection developed by the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis was calculated for the first episode of the infection that occurred within the specified time period after transplantation. To obtain an aggregate CI for each type of transplant, data from participating sites were weighted according to the proportion of transplants followed-up for specified time periods (four and 12 months for HSCT; six and 12 months for SOT). The aggregate CI of aspergillosis at 12 months was 0.5% after autologous HSCT, 2.3% after allogeneic HSCT from an HLA-matched related donor, 3.2% after transplantation from an HLA-mismatched related donor, and 3.9% after transplantation from an unrelated donor. The aggregate CI at 12 months was similar following myeloablative or non-myeloablative conditioning before allogeneic HSCT (3.1 vs. 3.3%). After HSCT, mortality at 3 months following diagnosis of aspergillosis ranged from 53.8% of autologous transplants to 84.6% of unrelated-donor transplants. The aggregate CI of aspergillosis at 12 months was 2.4% after lung transplantation, 0.8% after heart transplantation, 0.3% after liver transplantation, and 0.1% after kidney transplantation. After SOT, mortality at three months after diagnosis of aspergillosis ranged from 20% for lung transplants to 66.7% for heart and kidney transplants. The Aspergillus spp. associated with infections after HSCT included A. fumigatus (56%), A. flavus (18.7%), A. terreus (16%), A. niger (8%), and A. versicolor (1.3%). Those associated with infections after SOT included A. fumigatus (76.4%), A. flavus (11.8%), and A. terreus (11.8%). In conclusion, we found that invasive aspergillosis is an uncommon complication of HSCT and SOT, but one that continues to be associated with poor outcomes. Our CI figures are lower compared to those of previous reports. The reasons for this are unclear, but may be related to changes in transplantation practices, diagnostic methods, and supportive care.

Aspergillosis↗

The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis.

The term "aspergillosis" comprises several categories of infection: invasive aspergillosis; chronic necrotizing aspergillosis; aspergilloma, or fungus ball; and allergic bronchopulmonary aspergillosis. In 24 medical centers, we examined the impact of a culture positive for Aspergillus species on the diagnosis, risk factors, management, and outcome associated with these diseases. Most Aspergillus culture isolates from nonsterile body sites do not represent disease. However, for high-risk patients, such as allogeneic bone marrow transplant recipients (60%), persons with hematologic cancer (50%), and those with signs of neutropenia (60%) or malnutrition (30%), a positive culture result is associated with invasive disease. When such risk factors as human immunodeficiency virus infection (20%), solid-organ transplantation (20%), corticosteroid use (20%), or an underlying pulmonary disease (10%) are associated with a positive culture result, clinical judgment and better diagnostic tests are necessary. The management of invasive aspergillosis remains suboptimal: only 38% of patients are alive 3 months after diagnosis. Chronic necrotizing aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis have variable management strategies and better short-term outcomes.

Aspergillosis↗

Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey.

BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.

Adolescent↗

Hospital epidemiologic surveillance for invasive aspergillosis: patient demographics and the utility of antigen detection.

OBJECTIVE: To monitor the epidemiology of invasive aspergillosis at a university hospital during a period of hospital construction. To compare the efficacy of active epidemiologic surveillance for invasive aspergillosis using Aspergillus cultures with the efficacy of surveillance using Aspergillus antigen detection. DESIGN: A prospective surveillance study. SETTING: An 850-bed, tertiary-care, university-based hospital. PATIENTS: A convenience sample of 153 patients with Aspergillus antigen testing and culture. RESULTS: 24 cases were identified over a 12-month period; 7 were nosocomial, and 17 were community-acquired. Cases occurred primarily in patients with hematologic malignancy, but also occurred in patients with solid tumor, steroid treatment, cardiac transplant, and acquired immunodeficiency syndrome. Culture techniques identified only 14 (58%) of 24 cases, whereas Aspergillus antigen was positive in 19 (79%) of 24 cases tested. Epidemiological surveillance using either antigen or culture positivity detected 22 (92%) of 24 cases. In addition, antigen detection was 98% specific for the detection of aspergillosis, as compared to 91% for culture and 88% for antigen and culture combined. CONCLUSIONS: Hospital surveillance for aspergillosis should include determination of whether cases are nosocomial or community-acquired, because many may be the latter. Patients at risk for aspergillosis include patients without hematologic malignancies. Enhanced case detection occurred with active surveillance of patients considered to be at risk using both fungal serology and traditional microbiological techniques. Antigen detection was more sensitive and specific for the detection of invasive aspergillosis and may improve epidemiological surveillance for aspergillosis.

Antigens, Fungal↗

Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group.

A review of representative cases of invasive aspergillosis was conducted to describe current treatment practices and outcomes. Eighty-nine physicians experienced with aspergillosis completed case forms on 595 patients with proven or probable invasive aspergillosis diagnosed using modifications of the Mycoses Study Group criteria. Pulmonary disease was present in 56%, with disseminated infection in 19%. The major risk factors for aspergillosis were bone marrow transplantation (32%) and hematologic malignancy (29%), but patients had a variety of underlying conditions including solid organ transplants (9%), AIDS (8%), and pulmonary diseases (9%). Overall, high antifungal failure rates occurred (36%), and complete antifungal responses were noted in only 27%. Treatment practices revealed that amphotericin B alone (187 patients) was used in most severely immunosuppressed patients while itraconazole alone (58 patients) or sequential amphotericin B followed by itraconazole (93 patients) was used in patients who were less immunosuppressed than patients receiving amphotericin B alone. Response rate for patients receiving amphotericin B alone was poor, with complete responses noted in only 25% and death due to or with aspergillosis in 65%. In contrast, patients receiving itraconazole alone or following amphotericin B had death due to or with Aspergillus in 26% and 36%, respectively. These results confirm that mortality from invasive aspergillosis in severely immunosuppressed patients remains high even with standard amphotericin B. Improved responses were seen in the less immunosuppressed patients receiving sequential amphotericin B followed by itraconazole and those receiving itraconazole alone. New approaches and new therapies are needed to improve the outcome of invasive aspergillosis in high-risk patients.

Adolescent↗

Comparison of radiography and computed tomography for the diagnosis of canine nasal aspergillosis.

To compare the radiographic and computed tomographic (CT) findings and to evaluate the sensitivity of radiography and CT for diagnosis of nasal aspergillosis in dogs, the radiographic and CT studies of 48 dogs with chronic nasal disease were reviewed separately. The radiographic and CT findings were recorded, and a diagnosis was made. The results obtained in the dogs with nasal aspergillosis (n = 25) were used. Based on definite aspergillosis as diagnosis, CT had a sensitivity of 88% and radiography of 72%. Considering definite and probable aspergillosis as equivalent, CT had a sensitivity of 92% and radiography of 84%. The sensitivity was higher in dogs with lesions affecting the entire nasal cavity and frontal sinus on at least one side (n = 20) with a sensitivity of 100% for CT and 90-95% for radiography than in dogs with lesions restricted to the nasal cavities (n = 5) where CT had a sensitivity of 60-80% and radiography of 0-40%. CT was superior to radiography for evaluation of the nasal cavities (mucosal thickening along the nasal bones, surrounding bone hyperostosis/lysis), frontal sinuses (mucosal thickening along the frontal bone, fluid/soft tissue, frontal bone hyperostosis/lysis), and differentiation between a cavitated-like or a mass-like process. This study suggests that CT is more sensitive than radiography for diagnosis of nasal aspergillosis in the dog because of a better demonstration of some changes suggestive of nasal aspergillosis. A diagnosis of a nasal aspergillosis restricted to the nasal cavities or associated with an FB is challenging, even with the use of CT.

Animals↗

Evaluation of PCR for detection of DNA specific for Aspergillus species in sera of patients with various forms of pulmonary aspergillosis.

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.

Adult↗

Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a serious complication of cystic fibrosis and may be difficult to diagnose. The aim of this study was to define the usefulness of measuring total IgE compared with other major criteria in the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. METHODS: A retrospective analysis was carried out of the case records of 160 children attending a tertiary referral paediatric cystic fibrosis clinic. RESULTS: Sixteen children had a total IgE level above 500 IU/ml. Eleven children had six or more other major criteria and were considered to have allergic bronchopulmonary aspergillosis. These 11 children had a fourfold rise in IgE in association with clinical deterioration. A further child had a fourfold rise in IgE to 341 IU/l, and was also thought to have allergic bronchopulmonary aspergillosis. Eleven had a fall in IgE with successful treatment; one patient died with uncontrolled disease. Only one of these 12 children had negative precipitins to Aspergillus fumigatus. The five children with a raised IgE not thought to have bronchopulmonary aspergillosis had four or fewer major criteria and were not treated; none had positive precipitins. CONCLUSIONS: A fourfold rise in total IgE, particularly to above 500 IU/ml, is strongly suggestive of the diagnosis of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. The measurement of total IgE has the merit of being simple to perform and objective. Positive aspergillus precipitins provide useful confirmatory evidence. These two criteria, taken in conjunction with clinical deterioration and new radiological shadowing, allow simplification of the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Adolescent↗

Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings.

Aspergillosis is a serious pathologic condition caused by Aspergillus organisms and is frequently seen in immunocompromised patients. At computed tomography (CT), saprophytic aspergillosis (aspergilloma) is characterized by a mass with soft-tissue attenuation within a lung cavity. The mass is typically separated from the cavity wall by an airspace ("air crescent" sign) and is often associated with thickening of the wall and adjacent pleura. CT findings in allergic bronchopulmonary aspergillosis consist primarily of mucoid impaction and bronchiectasis involving predominantly the segmental and subsegmental bronchi of the upper lobes. Aspergillus necrotizing bronchitis may manifest as an endobronchial mass, obstructive pneumonitis or collapse, or a hilar mass. Bronchiolitis is characterized by centrilobular nodules and branching linear or nodular areas of increased attenuation ("tree-in-bud" pattern). Obstructing bronchopulmonary aspergillosis mimics allergic bronchopulmonary aspergillosis at CT and manifests as bilateral bronchial and bronchiolar dilatation, large mucoid impactions, and diffuse lower lobe consolidation caused by postobstructive atelectasis. Characteristic CT findings in angioinvasive aspergillosis consist of nodules surrounded by a halo of ground-glass attenuation ("halo sign") or pleura-based, wedge-shaped areas of consolidation. Although imaging findings in pulmonary aspergillosis may be nonspecific, in the appropriate clinical setting, familiarity with the CT findings may suggest or even help establish the diagnosis.

Aspergillosis, Allergic Bronchopulmonary↗

Invasive pulmonary aspergillosis: prediction at thin-section CT in patients with neutropenia--a prospective study.

PURPOSE: To evaluate prospectively the usefulness of thin-section computed tomography (CT) in the prediction of biopsy-proved invasive pulmonary aspergillosis in patients with neutropenia. MATERIALS AND METHODS: In 11 consecutively seen neutropenic patients, 12 open-lung biopsies were performed prospectively for suspected angioinvasive (n = 10) or airway-invasive (n = 2) pulmonary aspergillosis. Thin-section CT findings in the patients with angioinvasive pulmonary aspergillosis were reviewed, and the findings were compared with those of other diseases. RESULTS: Five of 12 biopsy specimens were positive for angioinvasive pulmonary aspergillosis; none was positive for airway-invasive pulmonary aspergillosis. In five (50%) of 10 cases, suspicion of angioinvasive pulmonary aspergillosis proved to be correct. The most common CT findings were segmental areas of consolidation plus ground-glass attenuation (four of five cases [80%]) and at least one nodule surrounded by a halo (two of five cases [40%]). Segmental areas of consolidation plus ground-glass attenuation were seen as isolated findings in three and mixed findings with nodules that have a surrounding halo in one case. In two patients, at least one nodule with a halo was an isolated finding in one patient and a mixed finding in one patient. Mucormycosis, organizing pneumonia, and pulmonary hemorrhage produced similar findings. CONCLUSION: At thin-section CT, segmental areas of consolidation plus ground-glass attenuation or at least one nodule with the halo sign were seen in patients with invasive pulmonary aspergillosis. The findings were nonspecific, however, and can be seen in neutropenic patients with mucormycosis, organizing pneumonia, or pulmonary hemorrhage.

Adolescent↗

Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases.

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality. In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA. Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation. Six patients with aplastic anemia were treated with antilymphocyte globulin. IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients. In only one case a diagnosis of IPA could be made preoperatively. Twenty patients underwent lobectomy and seven wedge resection. At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients. Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented. The median duration of surgery was 120 min. Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d. Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced. Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis). Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2). Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis. At 30 d postoperative mortality was 11% and 3-mo survival was 77%. After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA. In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.

Adolescent↗

Invasive aspergillosis in patients with hematologic malignancies.

Invasive aspergillosis is an increasingly common and often fatal opportunistic fungal infection in patients with hematologic malignancies. Prolonged and profound neutropenia remains a key risk factor for the development of invasive aspergillosis. However, qualitative deficiencies in host immune responses resulting from prolonged corticosteroid therapy, graft-versus-host disease, and cytomegalovirus infection are important risk factors for the recurrence and progression of Aspergillus infections after bone marrow recovery. Early diagnosis of invasive aspergillosis remains a challenge, and few tools are available for monitoring its course once the diagnosis is established. Even with the recent introduction of new antifungal therapies, mortality in patients with invasive aspergillosis remains high, and uniformly effective prophylaxis or preemptive therapeutic strategies are lacking. Strategies such as combination antifungal therapy and immunotherapy often are used as first-line treatment approaches in patients with documented invasive aspergillosis despite a paucity of clinical trial data. Recent advances in our understanding of the epidemiology, pathogenesis, and treatment of invasive aspergillosis in patients with hematologic malignancies are reviewed. The problems and controversies associated with defining optimal treatment strategies for invasive aspergillosis in this heavily immunocompromised population are highlighted.

Antifungal Agents↗