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      Actualización en Aspergilosis con énfasis en Aspergilosis invasora Translated title: Aspergillosis update with focus in invasive aspergillosis

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          Abstract

          El género Aspergillus es ubicuo en la naturaleza y de distribución universal. Por esta razón, el contacto con este hongo incluye hospederos inmunocompetentes e inmunosuprimidos. La vía aérea es la forma más frecuente de adquirir este hongo y sus manifestaciones clínicas y localización topográfica se relacionan con la interacción del hongo y la capacidad inmunológica del hospedero. La principal manifestación clínica de este hongo es a nivel respiratorio, con un impacto muy importante en mortalidad y morbilidad, especialmente en el paciente inmunosuprimido. Los pacientes con tumores hematológicos, trasplantes de corazón, pulmón y con sida son más susceptibles de presentar invasión tisular y vascular por este hongo, que en tales casos se manifiesta como Aspergilosis Invasora (AI). La AI ofrece dificultades diagnósticas en el hospedero inmunosuprimido por lo que en este grupo de pacientes el uso de métodos de diagnóstico no invasores permite guiar el abordaje terapéutico. En la actualidad se dispone de medicamentos antifúngicos del grupo de los azoles (voriconazol) y de las equinocandinas (caspofungina) que han mejorado el resultado de la AI. En este artículo se actualiza la literatura en cuanto al diagnóstico y tratamiento de la AI.

          Translated abstract

          The genus Aspergillus is ubiquitous in nature and has universal distribution; for this reason contact with this fungus includes immunocompetent and non-immunocompetent hosts. The most common form of acquiring this fungus is through air, and its clinical manifestations and topographic location correspond to the interaction of the fungus and its host's immune capacity. The main clinical manifestation of this fungus is a breathing condition and has a very significant impact on mortality and morbidity, especially in non-immunocompetent patients. Patients with haematological malignancies, heart or lung transplant surgeries, and AIDS are the most susceptible to present tissue and vascular invasion by this fungus in the form of invasive aspergillosis (IA). The IA presents diagnostic difficulties in non-immunocompetent hosts; therefore using non-invasive diagnosis methods for this group of patients offers therapeutic approach guidance. Antifungal drugs such as azoles (voriconazole) and echinocandins (caspofungin), that have improved the AI group results, are available nowadays. This article updates the literature on AI diagnosis and treatment.

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          Most cited references67

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          Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.

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            Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study.

            Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy. A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B. Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis). Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.
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              Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial.

              Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs. In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia. The median duration of neutropenia (neutrophil count, <500 cells/mm3) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; P < .05), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; P < .01). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%. Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                inf
                Infectio
                Infect.
                Asociación Colombiana de Infectología. (Bogotá )
                0123-9392
                December 2010
                : 14
                : suppl 2
                : s131-s144
                Affiliations
                [1 ] Universidad Nacional de Colombia Colombia
                [2 ] Instituto Nacional de Cancerología Mexico
                [3 ] del Instituto Nacional de Cancerología, Empresa Social del Estado
                Article
                S0123-93922010000600006
                4173146b-f50d-4f3d-8ad0-34fc371fd42e

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Colombia

                Self URI (journal page): http://www.scielo.org.co/scielo.php?script=sci_serial&pid=0123-9392&lng=en
                Categories
                INFECTIOUS DISEASES

                Infectious disease & Microbiology
                Invasive Aspergillosis,non-immunecompetent,diagnosis,treatment,Aspergilosis Invasora,inmunosupresión,diagnóstico,tratamiento

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