Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study

S Huygens, Albert Dunbar, Jochem B Buil, Corné H W Klaassen, Paul E Verweij, Karin van Dijk, Nick de Jonge, Jeroen J W M Janssen, Walter J F M van der Velden, Bart J Biemond, Aldert Bart, Anke H W Bruns, Pieter-Jan A Haas, Astrid M P Demandt, Guy Oudhuis, Peter von dem Borne, Martha T van der Beek, Saskia K Klein, Peggy Godschalk, Lambert F R SpanDouwe F Postma, Greetje A Kampinga, Johan Maertens, Katrien Lagrou, Toine Mercier, Ine Moors, Jerina Boelens, Dominik Selleslag, Marijke Reynders, Willemien Zandijk, Jeanette K Doorduijn, Jan J Cornelissen, Alexander F A D Schauwvlieghe, Bart J A Rijnders*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. 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).

Original languageEnglish
Pages (from-to)38-45
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume77
Issue number1
Early online date11 Mar 2023
DOIs
Publication statusPublished - 1 Jul 2023

Bibliographical note

Funding Information:
Financial support . This work was supported by Gilead Sciences, Inc, under grant number [IN-NL-131-4187].

Publisher Copyright:
© 2023 The Author(s).

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