https://hal.archives-ouvertes.fr/hal-01953645/document

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline

Rationale: The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. Objectives: We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. Methods: We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n=524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. Measurements and Main Results: Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to haveputative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). Conclusions: The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients. Copyright © 2012 by the American Thoracic Society.

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A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill Patients

Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

https://www.cell.com/trends/microbiology/pdf/S0966-842X(10)00021-1.pdf

Therapy for fungal diseases: opportunities and priorities

Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry.

7 Laboratoire d'Epidemiologie et de SantePublique, Faculted e Medecine, UniversiteLouis Pasteur, Strasbourg, France (See the editorial commentary by Kohno on pages XXX-XX) Background. Invasive aspergillosis is associated with high death rates. Factors associated with increased mor- tality have not yet been identified in a large population of patients with various underlying conditions. Methods. We retrospectively reviewed 385 cases of suspected or documented aspergillosis that occurred during a 9-year period. We identified 289 episodes that fulfilled the criteria for possible, probable, or proven invasive aspergillosis according to the international definition criteria and that was treated with an anti-Aspergillus active antifungal drug. Clinical and microbiological variables were analyzed for their effects on overall and attributable mortality. Significant variables in univariate analysis were introduced into a multivariate Cox model. Results. Twelve-week overall and disease-specific survival rates were 52.2% (95% confidence interval, 46.5%- 57.9%) and 59.8% (95% confidence interval, 54.0%-65.4%), respectively. Receipt of allogeneic hematopoietic stem cell or solid-organ transplant, progression of underlying malignancy, prior respiratory disease, receipt of corti- costeroid therapy, renal impairment, low monocyte counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion, and proven or probable (as opposed to possible) aspergillosis are predictors of increased overall mortality. Similar factors are also predictors of increased attributable mortality, with the following exceptions: pleural effusion and low monocyte counts have no impact, whereas neutropenia is associated with a higher attributable mortality. Conclusions. Identification of predictors of death helps in the identification of patients who could benefit from more-aggressive therapeutic strategies. Initiation of therapy at the stage of possible infection improves out- come, and this finding calls for the development of efficient preemptive strategies to fill the gap between empirical and directed therapy.

Factors Associated with Overall and Attributable Mortality in Invasive Aspergillosis

Patients suffering from acute leukemia are at high risk for invasive aspergillosis and a large review and a recent clinical trial have shown that they represent the largest group of patients developing the disease. New host groups such as patients with multiple myeloma or low-grade lymphoproliferative disorders have contributed to an increase in the incidence of invasive aspergillosis over recent years. There are substantial differences in the diagnostic strategy and therapeutic outcome of disease between patients with a hematological malignancy and other host groups such as allogeneic hematopoietic stem cell transplant patients. Galactomannan detection ELISA test is more specific in adult patients with hematological malignancies than in hematopoietic stem cell transplantation recipients. As a result of possible improvement of the underlying immune deficiency upon recovery from neutropenia, survival is higher in leukemic patients with invasive aspergillosis than in other host groups. However, there is currently no evidence of an effective antifungal prophylaxis strategy against aspergillosis in leukemic patients. As these patients account for a majority of the aspergillosis cases, clinical trials on prophylaxis should not only be focused on allogeneic stem transplant recipients but also be designed for the patient with leukemia.

Alireza Moghaddam

Papers

Factors Associated with Overall and Attributable Mortality in Invasive Aspergillosis

Invasive aspergillosis in the hematologic and immunologic patient: new findings and key questions in leukemia.

Prognostic Factors for Survival in Invasive Aspergillosis in Adult Oncohematological Patients.

Prognostic Value of Porta-Hepatis Lymphadenopathy in Children with Hepatitis A