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Aspergillus Spp Pilzinfektionen des Respirationstraktes/HNO-Trakt ÖQUASTA 2015, Igls/Austria Maria Aigner Sektion für Hygiene und Med. Mikrobiologie Innsbruck Klinische Einteilung der Pilze • D ermatophyten • H efepilze • S chimmelpilze Candidapneumonie? • Prospektive Studie über 2 Jahre an ICU-PatientInnen • Von 1.587 ICU-Pat. 301 verstorben (19%) • Mikroskopisch/histopathologische Untersuchung von Lungengewebe im Rahmen der Autopsie • 135 Pat. (58%) histopathologische Zeichen einer Pneumonie • 77 Pat. (57%) positiver Candida-Nachweis im Respirationstrakt • KEINE gesicherte Candida-Infektion Meersseman et al. Intensive Care Med 2009 Pilzinfektionen des Respirationstraktes/HNO-Trakt • D ermatophyten • H efepilze • S chimmelpilze Verteilung der Schimmelpilzspezies aus infektionsrelevanten Regionen Innsbruck 2014 4% 4% 6% Aspergillus spp. (83% A. fumigatus complex) 12% Penicillium spp. Dematiacaeous moulds Mucorales 74% Andere Pilze 91% aus BAL Erkrankungsformen der Aspergillose Kousha Eur Respir Rev 2011 Erkrankungsformen der Aspergillose Kousha Eur Respir Rev 2011 Clinical scenarios of Aspergillus overlap syndromes in the lungs. ABPA: allergic bronchopulmonary aspergillosis; IPA: invasive pulmonary aspergillosis; CNA: chronic necrotising aspergillosis ABPA • 2% of asthmatics (7–14% of corticosteroid-dependent asthmatics) • 1–15% of CF-patients • usually suspected on clinical grounds (episodic wheezing, expectoration of sputum containing brown plugs, pleuritic chest pain, fever) • confirmed by radiological and serological testing • positive sputum culture is not necessary • Aspergillus may rarely be detected on fungal stain or culture Kousha Eur Respir Rev 2011 ABPA Diagnostic criteria for allergic bronchopulmonary aspergillosis (Patterson criteria) Asthma Immediate cutaneous hyperreactivity on Aspergillus skin test (type I reaction) Precipitating antibodies (IgG) in serum against A. Sens.:42.7% fumigatus Spez.:97.1% Sens.: 100% Elevated serum A fumigatus specific IgE(>0.35 kUA/L) Spez.: 69.3% Sens.: 97.1% Elevated serum IgE >1000 IU/mL Spez.: 37.7% Transient or fixed pulmonary opacities Central bronchiectasis Agarwal et al. Eosinophilia (>1000 cells/mL) PLoS ONE 2013 Aspergilloma • cavitary lung diseases (tuberculosis, sarcoidosis, neoplasm,…) • does usually not invade the surrounding lung parenchyma or blood vessels • Most patients are asymptomatic • Haemoptysis, cough, dyspnoea, fever • diagnosis is usually based on clinical and radiographic features along with serological or microbiological evidence of Aspergillus spp. Aspergilloma • Sputum cultures for Aspergillus spp. are positive in 50% of cases • Serum IgG antibodies to Aspergillus are positive in most cases (~78%) but may be negative in patients on corticosteroid therapy • Aspergillus antigen has been recovered from the BAL fluid of patients with aspergilloma, but the diagnostic value of this test is variable Schweer et al. Mycoses 2014 Chronic Necrotising Aspergillosis (semi-invasive or subacute invasive aspergillosis) • local invasion by Aspergillus species • slowly progressive course over weeks to months • vascular invasion or dissemination to other organs is unusual • underlying chronic lung disease (COPD, previous pulmonary tuberculosis, sarcoidosis,…) • mildly immunocompromised (diabetes mellitus, alcoholism, chronic liver disease, low- dose corticosteroid therapy,…) • Aspergilloma may be seen in nearly 50% of patients Chronic Necrotising Aspergillosis (semi-invasive or subacute invasive aspergillosis) Diagnostic criteria Characteristics Clinical Chronic (>1 month) pulmonary or systemic symptoms, including at least one of: weight loss, productive cough or haemoptysis No overt immunocompromising conditions (e.g. haematological malignancy, neutropenia, organ transplantation) Radiological Cavitary pulmonary lesion with evidence of paracavitary infiltrate New cavity formation, or expansion of cavity size over time Laboratory Elevated levels of inflammatory markers (eg. CRP) Isolation of Aspergillus spp. from pulmonary or pleural cavity positive serum immunoglobulin (Ig)G antibodies to A. fumigatus, but this varies over time Exclusion of other pulmonary pathogens that are associated with similar disease presentation (eg. tuberculosis) Modified to Kousha Eur Respir Rev 2011 Invasive aspergillosis • severe and prolonged immunosuppression • AML during remission induction chemotherapy • Allogeneic HSCT • SOT • Medical ICU patients, especially those treated by corticotherapy Invasive aspergillosis Untersuchungstechnik Vor-/Nachteile Mikroskopie/Histologie • Beweisend für invasive Pilzinfektion, wenn Probenmaterial aus einer sterilen Region gewonnen wird • Kontamination ausgeschlossen • rasch • Unterscheidung zwischen septierten/nicht septierten Hyphen und Pseudohyphen Invasive aspergillosis Untersuchungstechnik Vor-/Nachteile Kultur • erst nach einigen Tagen positiv • unzureichende Sensitivität • Kontamination/Besiedelung/Allergie/Infektion? • Speziesidentifizierung • Resistenztestung Sens. Mikroskopie + Kultur in BAL ~ 50% in high-risk patients mit hämatologischer Grunderkrankung Aspergillus fumigatus Diagnostik Untersuchungstechnik ABPA CPA IPA Gaklaktomannan-Test (+) (+) + (Aspergillus-AG) Serum:1 Serum: 2 Serum:3 Sens.: 25.7% Sens.: 23% Sens.: 78% Spez.: 82% Spez.: 85% Spez.: 81% BAL: 4 7 Pat. (5 CNPA, BAL:5 Sens. Spez. 2 ABPA) Overall 87% 89% Sens.: 85.7% (33-100%) (52-100%) Spez.: 76.3% Proven IA 100% 77% Serum vs. 65% 95% BAL5 85% 86% 1 Agarwal et al. Mycoses 2015; 2 Shin et al. J Infect 2014; 3 Leeflang et al. Cochrane Database Syst Rev 2008; 4 Kono et a. Respiratory Medicine 2013; 5 Zou et al. PLoS ONE 2012 Diagnostik Untersuchungstechnik Vor-/Nachteile PCR • 10-100 Konidien/ml • Kontamination/ Kolonisation/Infektion? • Standardisierung??? Sens.: 58-80.5% Spez.: 78.5-95.2% 1 25% der BAL´s gesunder Personen positiv2 For patients at risk and highly suspicious of IPA 1 Cruciani et al. Cochrane 2015; 2 Tuon et al. Rev Iberoam Micol 2007 Penicillium spp. (außer P. marneffei) • ubiquitously present in the environment and usually considered as laboratory contaminants or non- pathogenic • Superficial infections (keratitis and otomycosis) • Allergic pulmonary disease • Seit 1951 31 Fälle von invasiven Infektionen – 12 pulmonary infection – 4 prosthetic valve endocarditis – 6 CAPD peritonitis – 5 endophthalmitis – oesophagitis (both in AIDS), upper urinary tract infection and intracranial infection Lyratzopoulos et al. J Infect 2002 Dematiaceous moulds “Schwärzepilze” • Localised cutaneous infection and subcutaneous nodules • Eumycotic mycetoma • Chromoblastomycosis • Keratitis • Pulmonary infections: pneumonia, pulmonary nodules and endobronchial lesions • Cerebral infection • Other localised deep infections (bone and joint infections, peritonitis) • Disseminated infection • Allergic fungal sinusitis: Bipolaris, Curvularia, Exserohilum, and Alternaria species • Allergic bronchopulmonary mycosis (ABPM): Bipolaris and Curvularia < 200 reported cases worldwide ESCMID/ECMM Guideline Diagnosis and Management of Systemic Phaeohyphomycosis: Diseases Caused by Black Fungi CMI 2014 Mucorales • Rhizopus spp., Lichtheimia (Absidia) spp., Mucor spp., Rhizomucor spp. • Granulocytopenia, immunosuppression, uncontrolled diabetes and penetrating trauma, prolonged use of corticosteroids • Rhinocerebral (39%), pulmonary (24%), cutaneous (19%), gastrointestinal, disseminated mucormycoses (23%) • high associated mortality rates – 96% of patients with disseminated infections – 85% with gastrointestinal infections – 76% with pulmonary infections • Fluconazole, voriconazole, echinocandins and flucytosine lack meaningful in vitro activity against Mucorales Resistenztestung MHK-Verteilung aller Aspergillus-Isolate (n=151) nach Anzahl Österreich 2014 AMB Amphotericin B; CAS Caspofungin; FLC Flucytosin; ITR Itraconazol, MIC Micafungin; POS Posaconazol, VOR Voriconazol KEINE in vitro Resistenz gegenüber Voriconazol 9% in vitro Resistenz gegenüber Amphotericin B 8% in vitro Resistenz gegenüber Posaconazol Danke für Ihre Aufmerksamkeit!.
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