Lore Vanderbeke1,2, Isabel Spriet3,4, Christine Breynaert5, Bart J A Rijnders6, Paul E Verweij7,8, Joost Wauters2,9. 1. KU Leuven Department of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology. 2. University Hospitals Leuven, Department of General Internal Medicine, Medical Intensive Care Unit. 3. KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Clinical Pharmacology and Pharmacotherapy. 4. University Hospitals Leuven, Department of Pharmacy. 5. KU Leuven Department of Microbiology and Immunology, Laboratory of Clinical Immunology, Leuven, Belgium. 6. Department of Internal Medicine, section of Infectious Diseases, Erasmus University Medical Center, Rotterdam. 7. Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen. 8. Centre of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, The Netherlands. 9. KU Leuven Department of Microbiology and Immunology, Laboratory for Clinical Infectious and Inflammatory Disorders, Leuven, Belgium.
Abstract
PURPOSE OF REVIEW: Bacterial super-infection of critically ill influenza patients is well known, but in recent years, more and more reports describe invasive aspergillosis as a frequent complication as well. This review summarizes the available literature on the association of invasive pulmonary aspergillosis (IPA) with severe influenza [influenza-associated aspergillosis (IAA)], including epidemiology, diagnostic approaches and treatment options. RECENT FINDINGS: Though IPA typically develops in immunodeficient patients, non-classically immunocompromised patients such as critically ill influenza patients are at high-risk for IPA as well. The morbidity and mortality of IPA in these patients is high, and in the majority of them, the onset occurs early after ICU admission. At present, standard of care (SOC) consists of close follow-up of these critically ill influenza patients with high diagnostic awareness for IPA. As soon as there is clinical, mycological or radiological suspicion for IAA, antifungal azole-based therapy (e.g. voriconazole) is initiated, in combination with therapeutic drug monitoring (TDM). Antifungal treatment regimens should reflect local epidemiology of azole-resistant Aspergillus species and should be adjusted to clinical evolution. TDM is necessary as azoles like voriconazole are characterized by nonlinear pharmacokinetics, especially in critically ill patients. SUMMARY: In light of the frequency, morbidity and mortality associated with influenza-associated aspergillosis in the ICU, a high awareness of the diagnosis and prompt initiation of antifungal therapy is required. Further studies are needed to evaluate the incidence of IAA in a prospective multicentric manner, to elucidate contributing host-derived factors to the pathogenesis of this super-infection, to further delineate the population at risk, and to identify the preferred diagnostic and management strategy, and also the role of prophylaxis.
PURPOSE OF REVIEW: Bacterial super-infection of critically ill influenzapatients is well known, but in recent years, more and more reports describe invasive aspergillosis as a frequent complication as well. This review summarizes the available literature on the association of invasive pulmonary aspergillosis (IPA) with severe influenza [influenza-associated aspergillosis (IAA)], including epidemiology, diagnostic approaches and treatment options. RECENT FINDINGS: Though IPA typically develops in immunodeficientpatients, non-classically immunocompromised patients such as critically ill influenzapatients are at high-risk for IPA as well. The morbidity and mortality of IPA in these patients is high, and in the majority of them, the onset occurs early after ICU admission. At present, standard of care (SOC) consists of close follow-up of these critically ill influenzapatients with high diagnostic awareness for IPA. As soon as there is clinical, mycological or radiological suspicion for IAA, antifungal azole-based therapy (e.g. voriconazole) is initiated, in combination with therapeutic drug monitoring (TDM). Antifungal treatment regimens should reflect local epidemiology of azole-resistant Aspergillus species and should be adjusted to clinical evolution. TDM is necessary as azoles like voriconazole are characterized by nonlinear pharmacokinetics, especially in critically illpatients. SUMMARY: In light of the frequency, morbidity and mortality associated with influenza-associated aspergillosis in the ICU, a high awareness of the diagnosis and prompt initiation of antifungal therapy is required. Further studies are needed to evaluate the incidence of IAA in a prospective multicentric manner, to elucidate contributing host-derived factors to the pathogenesis of this super-infection, to further delineate the population at risk, and to identify the preferred diagnostic and management strategy, and also the role of prophylaxis.
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Authors: Oscar Fernández García; Lorena Guerrero-Torres; Carla M Roman-Montes; Andrea Rangel-Cordero; Areli Martínez-Gamboa; Alfredo Ponce-de-León; María F González-Lara Journal: Med Mycol Case Rep Date: 2021-07-09