Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study.
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Huygens Sammy, Dunbar Albert, Buil Jochem B, Klaassen Corné H W, Verweij Paul E, van Dijk Karin, de Jonge Nick, Janssen Jeroen J W M, van der Velden Walter J F M, Biemond Bart J, Bart Aldert, Bruns Anke H W, Haas Pieter-Jan A, Demandt Astrid M P, Oudhuis Guy, von dem Borne Peter, van der Beek Martha T, Klein Saskia K, Godschalk Peggy, Span Lambert F R, Postma Douwe F, Kampinga Greetje A, Maertens Johan, Lagrou Katrien, Mercier Toine, Moors Ine, Boelens Jerina, Selleslag Dominik, Reynders Marijke, Zandijk Willemien, Doorduijn Jeanette K, Cornelissen Jan J, Schauwvlieghe Alexander F A D, Rijnders Bart J A
Аннотация
METHODS: In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA.
RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83).
CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).