Invasive pulmonary aspergillosis in patients with neoplastic diseases

Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in granulocytopenic patients. The purpose of this article is to review the current understanding of the microbiology, hospital epidemiology, clinical manifestations, diagnosis, prevention, and treatment of invasive pulmonary aspergillosis. Aspergillus conidia (spores) are inhaled from environmental sources into the paranasal sinuses and lower respiratory tract. Persistent fever, pulmonary infiltrates, and pleuritic pain in granulocytopenic patients receiving antibacterial antibiotics is a common manifestation of invasive pulmonary aspergillosis. Computerized tomographic scans of the chest often reveal characteristic peripheral nodules that also may progress to characteristic cavitary lesions. Hemoptysis may develop due either to hemorrhagic infarction during granulocytopenia or to the rupture of mycotic aneurysms during recovery from granulocytopenia. Aspergillus organisms may extend locally from the lung to involve other thoracic structures, including the heart and chest wall, and may disseminate to extrapulmonary sites, such as the brain, where focal neurological deficits ensue. Early diagnosis of invasive pulmonary aspergillosis may be difficult. Isolation of Aspergillus organisms from respiratory secretions of a persistently febrile granulocytopenic patient is usually indicative of invasive pulmonary aspergillosis and should not be dismissed as a contaminant or saprophyte. Amphotericin B is the treatment of choice; however, high dosages (1.0 to 1.5 mg/kg/day) are often necessary. Aspergillosis may develop in granulocytopenic patients who are already receiving empirical amphotericin B in lower doses (0.5 to 0.6 mg/kg/day). It is hoped that further investigation directed toward an understanding of pathogenesis, improving diagnostic methodology, and developing new therapeutic and preventive strategies will improve the outcome of this life-threatening infection.     

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

Aspergillus spp. cultured in specimens from the airways of chronic obstructive pulmonary disease (COPD) patients are frequently considered as a contaminant. However, growing evidence suggests that severe COPD patients are at higher risk of developing invasive pulmonary aspergillosis (IPA), although IPA incidence in this population is poorly documented. Some data report that COPD is the underlying disease in 1% of patients with IPA. Definitive diagnosis of IPA in COPD patients is often difficult as tissue samples are rarely obtained before death. Diagnosis is therefore usually based on a combination of clinical features, radiological findings (mostly thoracic computed tomography scans), microbiological results and, sometimes, serological information. Of 56 patients with IPA reported in the literature, 43 (77%) were receiving corticosteroids on admission to hospital. Breathlessness was always a feature of disease and excess wheezing was present in 79% of patients. Fever (>38 degrees C) was present in only 38.5%. Chest pain and haemoptysis were uncommon. Six out of 33 (18%) patients had tracheobronchitis observed during bronchoscopy. The median delay between symptoms and diagnosis was 8.5 days. The mortality rate was high: 53 out of 56 (95%) patients died despite invasive ventilation and antifungal treatment in 43 (77%) of them. In chronic obstructive pulmonary disease patients, invasive pulmonary aspergillosis currently carries a very poor prognosis. Outcome could perhaps be improved by more rapid diagnosis and prompt therapy with voriconazole.     

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease

Background

Invasive pulmonary aspergillosis (IPA) is an infection often occurring in neutropenic patients and has high mortality rates. In recent years, it has been reported that the incidence of IPA has also increased in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the clinical and demographic characteristics and treatment responses of IPA in patients with COPD.

Methods

Seventy-one patients with a positive culture of Aspergillus from lower respiratory tract samples were examined retrospectively. Eleven (15.4%) of these patients, affected with grade 3 or 4 COPD, had IPA.

Results

Aspergillus hyphae were detected in lung biopsy in three (27.3%) out of 11 patients and defined as proven IPA; a pathological sample was not taken in the other eight (72.7%) patients, and these were defined as probable IPA. Aspergillus isolates were identified as six cases of Aspergillusfumigatus and three of Aspergillusniger in nine patients, while two isolates were not identified at species level. While five patients required intensive care unit admission, four of them received mechanical ventilation. The most common finding on chest X-ray and computed tomography (CT) (respectively 63.6%, 72.7%) was infiltration. Amphotericin B was the initial drug of choice in all patients and five patients were discharged with oral voriconazole after amphotericin B therapy. Six patients (54.5%) died before treatment was completed.

Conclusions

IPA should be taken into account in the differential diagnosis particularly in patients with severe and very severe COPD presenting with dyspnea exacerbation, poor clinical status, and a new pulmonary infiltrate under treatment with broad-spectrum antibiotics and steroids.

     

Invasive aspergillosis

Invasive fungal disease of humans caused by species of the genus Aspergillus Micheli ex Linnaeus has become a significant and prevalent problem in contemporary medicine, particularly with regard to the compromised host. This review addresses the current status of invasive aspergillosis, including microbiological, clinical, and pathologic aspects. Diagnostic and therapeutic considerations are discussed with a view toward early and aggressive intervention in order to prevent the high mortality rate associated with aspergillosis.     

Invasive aspergillosis in critically ill patients without malignancy

Using criteria designed for invasive aspergillosis (IA) in patients with cancer, we aimed to determine the impact of IA in patients without malignancy in a medical intensive care unit (ICU). In this retrospective study, 127 patients out of 1,850 admissions (6.9%) hospitalized between 2000 and 2003 had microbiological or histopathologic evidence of Aspergillus during their ICU stay. There were 89 cases (70%) without hematologic malignancy. These patients were classified as proven IA (n = 30), probable IA (n = 37), possible IA (n = 2), or colonization (n = 20). In these patients, mean SAPS II score was 52 with a predicted mortality of 48%. The observed mortality was 80% (n = 71). Mortality of the proven and the probable IA was 97 and 87%, respectively. Postmortem examination was done in 46 out of 71 patients, and 27 autopsies (59%) showed hyphael invasion with Aspergillus. Aspergillus infections occurred in five critically ill patients with proven IA who did not have any predisposing factors according to the currently available definitions. Three of these patients had Child C liver cirrhosis. IA is an emerging and devastating infectious disease in patients in the ICU without malignancy. In those patients, host criteria for probable fungal infections should probably be adapted.     

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series

Background

Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis.

Case presentation

We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment.

Conclusion

Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.     

Invasive pulmonary aspergillosis in a puerperant with drug-induced agranulocytosis.

Invasive pulmonary aspergillosis (IPA) is an acute infection of Aspergillus species to the lungs. It generally occurs in immunocompromised hosts, especially with neutropenia. We report a 30-year-old puerperant, who developed IPA from agranulocytosis. She had been treated for threatened labor with ritodrine and cefepime, one of which induced agranulocytosis. After vaginal delivery of twins, pneumonia emerged in the right lower lobe. She was diagnosed to have IPA according to the halo sign on computed tomography (CT) and positive circulating antibody against Aspergillus, and was treated successfully with oral itraconazole followed by surgical resection. It is important to note that IPA might arise in otherwise immunocompetent hosts when neutropenia is long-standing.     

Invasive pulmonary aspergillosis

BACKGROUND: Invasive pulmonary aspergillosis usually occurs in immunocompromised patients. Mild abnormality of host defence is usually present in the chronic necrotising form of the disease. Acute aspergillus pneumonia usually affects patients who are seriously immunocompromised. OBJECTIVES: The purpose of the study was to highlight the possibility of occurrence of invasive pulmonary aspergillosis also in patients with mild abnormality of host defence. METHODS: In a retrospective study 6 patients were analysed. The inclusion criterion was evidence of Aspergillus sp. invasion in lung tissue. Lung tissue was obtained by biopsy or post mortem examination. RESULTS: There were 4 patients with acute aspergillus pneumonia. Two of them were severely immunocompromised - one with dermatomyositis, who was treated with high doses of corticosteroids and methotrexate, and the other with undiscovered miliary tuberculosis, who was treated for myelodysplastic syndrome instead with low doses of corticosteroids. The other 2 had mild immunosuppression: one was suffering from sarcoidosis and was treated with low doses of corticosteroids, the other had dilated cardiomyopathy, renal insufficiency and diabetes mellitus. The two patients with chronic necrotising pulmonary aspergillosis had mild abnormality of host defence: one had reactivation of tuberculosis and diabetes mellitus, the other had inactive tuberculosis and aspergilloma. CONCLUSIONS: Invasive pulmonary aspergillosis must be considered also in patients with mild immunosuppression and pulmonary infiltrates which do not respond to conventional treatment with antibiotic chemotherapy. The key to the diagnosis of invasive pulmonary aspergillosis is the histopathological demonstration of fungal invasion in lung tissue.     

Invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients. The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy. The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options. Research efforts are being made constantly to improve different diagnostic techniques. Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles.     

Invasive aspergillosis in children with acquired immunodeficiencies

Invasive aspergillosis has emerged as an important cause of morbidity and mortality in immunocompromised children. It remains difficult to diagnose, and outcome depends on early diagnosis, appropriate treatment, and restoration of host defenses. Pediatric patients represent a unique population in their clinical presentation and epidemiology, particularly in respect to the utility of newer diagnostic tools and the pharmacokinetics of antifungal agents. This article reviews the presentation and epidemiology of invasive aspergillosis in children and adolescents with acquired immunodeficiencies and discusses the value of current diagnostic tools and the options for treatment and prevention in this population.     

Invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) is the most common fungal pulmonary infection in severely immunocompromised patients. Aspergillus species are commonly isolated from the soil, plant debris, and the indoor environment, including the hospital. Phagocytosis is the main host defense against Aspergillus conidia and hyphae. The diagnosis of IPA is based on clinical, radiological, and mycological data. Clinical signs have a low specificity. The most typical computed tomographic (CT) findings are nodules with or without the halo sign or the air crescent sign. Sensitivity of microscopy and culture of noninvasive collected samples is low. Galactomannan and nucleic acid detection in serum or in bronchoalveolar lavage (BAL) fluid help to confirm the diagnosis. Crude mortality is high and strongly correlated with the underlying condition, stage of the underlying disease, and extension of the aspergillosis. Optimal therapeutic strategies include the prevention of contamination in patients at high risk, early initiation of antifungal therapy, surgery in some instances, and, importantly, treatment of the underlying condition to restore whenever possible a certain degree of immunocompetence. Voriconazole has demonstrated better efficacy and safety than amphotericin B deoxycholate. The improved survival observed with voriconazole makes it a new reference for the first-line therapy of IA. Lipid formulations of amphotericin B, caspofungin, micafungin, and posaconazole are other therapeutic options in the event of failure of or contraindication to voriconazole. The main indication for surgery is prevention of severe hemoptysis when the lesion is adjacent to a large vessel.     

Invasive pulmonary aspergillosis complicating neoplastic disease.

Invasive pulmonary aspergillosis is a necrotizing pneumonia that is most frequently seen in association with profound granulocytopenia as a consequence of cytotoxic chemotherapy that is used to treat hematologic neoplasms. There is considerable evidence that the incidence of this infection is increasing over the past decade as a result of improved medical support used in the management of "at risk" patients. Heightened clinical awareness coupled with advances in diagnostic techniques have led to earlier treatment and improved outcomes of this once uniformly fatal infection. Amphotericin B remains the treatment of choice; however, newer therapeutics (azoles) and strategies (combination chemotherapy, biological response modifiers) show promise as alternative regimens. Novel approaches in preventing the acquisition of pulmonary aspergillosis in the "at risk" patient are being explored.     

Invasive nosocomial pulmonary aspergillosis

Immunodepressed patients, particularly those with neutropenia or bone marrow or organ grafts, are at risk of developing nosocomial invasive pulmonary aspergilosis. The favoring factors, early diagnostic criteria and curative treatment protocols are well known. Prognosis remains however quite severe with a death rate above 50%. Preventive measures are required for the treatment of these high-risk patients and epidemiology surveillance is needed in case of aspergillosis acquired in the hospital.     

Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors

BACKGROUND AND OBJECTIVES: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors. DESIGN AND METHODS: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed. RESULTS: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003). INTERPRETATION AND CONCLUSIONS: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.     

Invasive pulmonary aspergillosis associated with influenza B

Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised patients. However, rarely, this infection can occur in normal hosts. This review of the literature identified 13 cases of IPA associated with influenza, of which 12 had influenza A and the type of influenza was not mentioned in the other case. Reported here is a case of IPA, which was associated with influenza B, in a 63-year-old immunocompetent woman. Her lungs showed gross invasion and she was treated with itraconazole and amphotericin B. She required mechanical ventilation for about 5 months but recovered completely. This is the first reported case of IPA associated with influenza B.