Invasive aspergillosis: treatment

Invasive aspergillosis is a severe disease, affecting essentially congenital or acquired immunodepressed patients, as well as neutropenic or transplanted ones, and those undergoing prolonged chemotherapy or treatment with corticoids. At present, the physician only disposes of the following treatment: amphotericin B desoxycolate, lipidic amphotericins and itraconazole p.o. or intravenously. Very soon, other drugs like voriconazole, posaconazole, liposomal nystatin and echinocandins probably will have a role in the treatment. It is most important to know thoroughly the patients's base disease and its specific treatment and the role of the drugs at present available, their relevant dosage, biodisponibility and pharmacokinetics, as well as adverse effects and evidence-based criterions of application. It is very important indeed to maintain a high suspicion of the disease and a rapid start of treatment. It is equally important to assess the role of coadjuvant treatments. We insist in the importance of surgery in solving of the disease in some cases (progressive pulmonar aspergillosis, sinusitis) combined with appropriate antifungal treatment.     

Invasive pulmonary aspergillosis in AIDS.

Aspergillosis is a fungal infection rarely observed in Cuba during the first years of the AIDS epidemic. However, the increase in aspergillosis cases diagnosed by autopsy in recent years, led us to study the epidemiological, clinical, radiological and anatomopathological characteristics of this disease among the Cuban AIDS patients. A total of 307 autopsies were reviewed, seven of them had invasive pulmonary aspergillosis (2.2%). The disease was predominant in men and in the white race. Neutropenia and drugs use were the risk factor more frequently observed. Clinical manifestations were those unspecific and common to other opportunistic infection of the respiratory system. The more common radiological picture were bilateral nodular infiltrates and cavitary lesions in the upper lobes (two cases). The anatomopathological diagnosis was based on the morphological characteristics of the agent and in the angioinvasive features of the pulmonary lesions. We suggest that aspergillosis should be considered in the differential diagnosis of opportunistic respiratory events of AIDS patients in advanced stages.     

Invasive aspergillosis: clinical manifestations and treatment

During the last decade the incidence of invasive aspergillosis has substantially grown due to the increasing use of powerful immunosupressive drugs in more patients. Unfortunately, the associated mortality with this infection is still very high and has not decreased in recent years. Pulmonary aspergillosis is by far the most frequent clinical picture of this infection, followed by sinus, tracheo-bronchial and central nervous system disease. The degree of immunosupression is the main factor influencing the evolution and dissemination of aspergillosis. Conventional amphotericin B has been the first-line therapy of invasive aspergillosis for the last 30 years, and most authors have long considered amphotericin B related toxicity as one of the main causes for the poor results obtained in the outcome of patients who developed this infection. Fortunately, in the last few years new safer and more effective drugs have been developed for the treatment of this entity. However, if we are really trying to substantially decrease invasive aspergillosis associated-mortality we should use these drugs earlier in the development of the infection, using new more sensitive diagnostic tests and/or a riskbase strategy which could identify patients at the highest risk to develop this infection.     

Invasive aspergillosis in a "healthy" patient.

A case of invasive aspergillosis complicated by the formation of an aspergilloma is described. The patient, a 48-year-old man, was apparently healthy except for mild alcoholic steatosis of the liver. A review of the literature revealed that 5 of the 14 previously reported cases of invasive aspergillosis in seemingly immunocompetent hosts were associated with liver disease. Immunologic investigation in this case revealed transient cutaneous anergy during the acute illness and normal lymphocyte function. Assessment of polymorphonuclear leukocyte function, however, showed abnormalities of phagocytosis as well as impairment of intracellular bactericidal activity. These abnormalities may have contributed to a relative immunodeficiency. Impairment of immune function may play a role in the pathogenesis of invasive aspergillosis in some apparently healthy patients.     

Invasive pulmonary aspergillosis: retrospective case record review

Invasive pulmonary aspergillosis is a severe infection, with a sharp increase during the last decades. Our study aimed at identification of the epidemiological characteristics of invasive pulmonary aspergillosis during a period of four years. All clinical records with pulmonary isolation of Aspergillus species were reviewed, as a part of surveillance program at Reina Sofia University Hospital, from January 1995 to December 1998. Diagnosis of invasive pulmonary aspergillosis was based on criteria of Centers for Disease Control and Prevention. Of the 50 patients identified 78% were males and 44% were current or ex-smokers. Chronic respiratory diseases were identified in 64% of them, and 60% were receiving immunosuppressives. Twenty percent of our patients had been subjected to lung transplantation and 28% to organ transplantation in general. Only 78% had received specific antifungal treatment and 56% had fatal prognosis. Our findings match with previous studies, apart from the high frequency of lung transplantation in our series. We recommend further studies on large prospective cohorts.     

Bronchoalveolar lavage in an immunosuppressed rabbit model of invasive pulmonary aspergillosis

A rabbit model of invasive aspergillosis has been used to investigate the pathogenesis of Aspergillus infection in the immunosuppressed host. The animals received hydrocortisone daily and a single dose of cyclophosphamide 2 days prior to intratracheal instillation of conidia from Aspergillus fumigatus. Bronchoalveolar lavage (BAL) was performed in 3 infected and 2 control saline treated animals sacrificed on days 1, 2, 4, 7 and 10 following inoculation. Infective load within the lung was quantified using an assay for chitin which is an important component of fungal cell walls (in particular the hyphal cell wall) and is not present in vertebrate tissue. The total BAL white cell count did not discriminate between infected and saline treated animals and Aspergillus was cultured from one lavage specimen only. Infected animals developed a marked neutrophil alveolitis by day 2 in contrast to a near total absence of neutrophils in the lavages of the control animals. Phagocytosis of conidia by alveolar macrophages was prominent but did not prevent progressive infection as confirmed by measurement of lung chitin. This pattern of cellular response within the alveolar airspace reflects the complex nature of the response to Aspergillus infection in the immunosuppressed host.     

Cutaneous candidosis in immunosuppressed patients

One-hundred patients with candidosis of the skin, mucous membranes and nail plates (confirmed by cultivation) were examined. Topical or systemic antimycotic treatment was successful in 58 patients. After a complete evaluation, 42 patients were found to suffer from factors supporting candidosis —diabetes mellitus (12), anemia (3) and various local factors (10 patients); 27 patients showed a deficiency in cell-mediated immunity. In addition to intensive antimycotic therapy, successful treatment is affected by the actual immunity level and can be ensured by efficient immunomodulation treatment of immuno-deficiency.     

Invasive aspergillosis with extrapulmonary involvement: pathogenesis, clinical characteristics and prognosis

BackgroundThe incidence of invasive aspergillosis has increased worldwide. Information regarding the clinical characteristics of patients with extrapulmonary involvement is scarce.ObjectiveWe aimed to describe the pathogenesis, characteristics and outcomes of patients with invasive aspergillosis and extrapulmonary disease.MethodsA retrospective study conducted in a university hospital in Barcelona, Spain (1995-2011).ResultsA total of 12 cases of invasive aspergillosis and extrapulmonary involvement were found. The most common clinical manifestations were invasive sinusitis, early postoperative prosthetic valve endocarditis, fungaemia, postoperative meningitis, multiple brain abscesses and lumbar spondylitis with epidural abscess. Sinusitis occurred frequently in patients without immunosuppression and had invasive brain involvement in one case. Endocarditis was associated with multiple septic metastases. Concomitant lung involvement was documented in 5 cases. The strains isolated were Aspergillus fumigatus (5), Aspergillus flavus (3), and Aspergillus niger (2). The species of Aspergillus was not established for 3 isolates. All patients were treated with antifungals and surgery was performed in 8 cases. Outcome was related with the source of infection; all patients with invasive sinusitis survived, while the remaining patients had a high mortality rate (88%).ConclusionsInvasive aspergillosis with extrapulmonary involvement is rare. The most common presentation is invasive sinusitis, which has a lower mortality. Other clinical forms with extrapulmonary involvement were associated with severe immunosuppression or previous surgery, and had a poor outcome.     

COVID-19 prophylaxis in immunosuppressed patients: Beyond vaccination

Ivan Gentile and Nicola Schiano Moriello discuss the potential of monoclonal antibody prophylaxis against COVID-19 infection in immunocompromised patients.