Aufgrund der in dieser Studie gewonnen Daten zur Prävalenz von ARAF bei CF-PatientInnen sollten CF-PatientInnen, die eine Azoltherapie erhalten sollen und/oder für eine Lungentransplantation gelistet sind, auf die Präsenz von A. fumigatus getestet und folgend auf eine Azol-Resistenz hin untersucht werden. Weiterhin sollte eine ausreichende Anzahl an Isolaten unabhängig vom Risikoprofil der PatientInnen getestet werden, um die lokale Resistenzlage beurteilen zu können.
Dafür sind phänotypische Screening-Verfahren mittels Azol-Agar das Mittel der Wahl.
Hier kann auch aufgrund der geringen Rate an Itraconazol-sensiblen Isolaten ohne Kreuzresistenz die Verwendung eines reinen Itraconazol-Agars erwogen werden.
Konform mit den Expertenempfehlungen zu ARAF bei invasiver Aspergillose sollte ab einem Grenzwert von 10% ARAF eine Erstlinien-Monotherapie mit Triazolen neu erwogen werden (Verweij et al., 2015; Verweij et al., 2016).
Hier werden eine Monotherapie mit Amphotericin B sowie eine Kombinationstherapie aus Triazol und Echinocandin als Therapiansätze diskutiert und von Leitlinien empfohlen. Der Nachteil einer Amphotericin B-Therapie liegt in der fehlenden Evidenz zur gleichwertigen Wirksamkeit von Amphotericin B im Vergleich zu Voriconazol bei Azol-sensiblen Isolaten (Verweij et al., 2015). Unklar bleibt die Bedeutung für die Entscheidung über die Durchführung einer Azolprophylaxe (P. P. A. Lestrade et al., 2019).
9 Zusammenfassung
Infektionen mit Aspergillus fumigatus stellen eine zunehmende Bedrohung für immunsupprimierte und chronisch erkrankte Patientinnen und Patienten aller Altersstufen dar. Mit zunehmend aufzufindender Resistenz gegenüber der vielgenutzten und gut verträglichen Gruppe der Azol-Antimykotika verringern sich Therapieoptionen auf Zweitlinienempfehlungen mit weniger Evidenz zur Heilungsrate.
Der Fokus dieser Arbeit lag auf der Erfassung der Resistenzlage von Aspergillus fumigatus sensu stricto in der besiedelteln Population der Zystische Fibrose-PatientInnen. Diese erste multizentrische Untersuchung fand in 2888 Isolaten von 961 PatientInnen aus zwölf Zentren eine Resistenzprävalenz von 5,3% in Deutschland. Eindeutige Risikofaktoren für eine Besiedelung mit Azol-resistenem Aspergillus fumigatus konnten in dieser Arbeit nicht ausgemacht werden. Die meisten Pilzisolate wiesen eine Panresistenz gegenüber allen Azolpräparaten, auch dem neuen Präparat Isavuconazol, auf.
Einzelne Isolate zeigten auch zentrenübergreifend genotypische Verwandtschaft, wie zuvor in anderen Studien gezeigt werden konnte.
Für die klinische Routine wird aus den gewonnenen Ergebnissen geschlossen, dass eine Erhebung der lokalen Resistenzlage in Kliniken mit gefährdetem Patientengut also sinnvoll zu erachten ist. Eine phänotypische Testung wird als ausreichend angesehen, sollte jedoch mit ausreichender Erfahrung der UntersucherInnen angewandt werden.
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