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Multicenter Study
. 2023 Jul 5;77(1):38-45.
doi: 10.1093/cid/ciad141.

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

Sammy Huygens  1 , Albert Dunbar  1 , Jochem B Buil  2 , Corné H W Klaassen  3 , Paul E Verweij  2 , Karin van Dijk  4 , Nick de Jonge  5 , Jeroen J W M Janssen  5 , Walter J F M van der Velden  6 , Bart J Biemond  5 , Aldert Bart  4 , Anke H W Bruns  7 , Pieter-Jan A Haas  8 , Astrid M P Demandt  9 , Guy Oudhuis  10 , Peter von dem Borne  11 , Martha T van der Beek  12 , Saskia K Klein  13   14 , Peggy Godschalk  15 , Lambert F R Span  14 , Douwe F Postma  16 , Greetje A Kampinga  17 , Johan Maertens  18   19 , Katrien Lagrou  19   20 , Toine Mercier  18   19 , Ine Moors  21 , Jerina Boelens  22 , Dominik Selleslag  23 , Marijke Reynders  24 , Willemien Zandijk  3 , Jeanette K Doorduijn  25 , Jan J Cornelissen  25 , Alexander F A D Schauwvlieghe  23 , Bart J A Rijnders  1
Affiliations
Multicenter Study

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

Sammy Huygens et al. Clin Infect Dis. .

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).

Keywords: Aspergillus PCR; azole resistance; clinical impact; invasive aspergillosis.

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Conflict of interest statement

Potential conflicts of interest J. M. reports grants from Gilead Sciences, Inc; consulting fees, payment for lectures/presentations, and support for meetings/travel expenses from Gilead Sciences, Inc, MSD, Pfizer, Takeda, and F2G; and participation on a data safety monitoring board or advisory board for Gilead Sciences, Inc, MSD, Pfizer, Takeda, F2G, and Cidara. P. G. reports partial support for travel to Trends In Medical Mycology conference. K. L. reports grants from Thermo Fisher Scientific and TECOmedical paid to their institution; consulting fees from Gilead, MSD, and MRM Health, all paid to their institution; and personal fees for lectures/presentations for Pfizer, Gilead, and FUJIFILM Wako. M. R. reports support for travel to Trends In Medical Mycology conference. J. J. reports grants from Novartis and BMS, both paid to their institution; payment for lectures from AbbVie, Novartis, Pfizer, and Incyte; and serving as president of the Apps for Care and Science, a nonprofit organization, supported by AbbVie, Alexion, Amgen, Astellas, BMS, Daiichi-Sankyo, Janssen-Cilag, Olympus, Incyte, Sanofi Genzyme, Servier, Jazz, and Takeda. J. B. reports research grants from Gilead Sciences, Inc, and F2G. P. V. reports research grants from F2G and Gilead, paid to their institution; honoraria for lectures from F2G, Gilead, and Pfizer, all paid to their institution; and participation on a data safety monitoring board for F2G, paid to their institution. S. H. reports support from Gilead for travel to the International Society for Human and Animal Mycology 2022 conference. B. R. reports research grants from Gilead Sciences, Inc; support for meetings/travel expenses from Gilead Sciences, Inc, F2G, and Pfizer; consulting fees from F2G; payment/honoraria for lectures/presentations from Gilead Sciences, Inc; and participation on a data safety monitoring board/advisory board for Exevir. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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References

    1. Herbrecht R, Denning DW, Patterson TF, et al. . Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347:408–15. - PubMed
    1. Maertens JA, Marr KA II, Patterson TF, et al. . Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2016; 387:760–9. - PubMed
    1. Lestrade PP, van der Velden W, Bouwman F, et al. . Epidemiology of invasive aspergillosis and triazole-resistant Aspergillus fumigatus in patients with haematological malignancies: a single-centre retrospective cohort study. J Antimicrob Chemother 2018; 73:1389–94. - PubMed
    1. Lestrade PP, Bentvelsen RG, Schauwvlieghe A, et al. . Voriconazole resistance and mortality in invasive aspergillosis: a multicenter retrospective cohort study. Clin Infect Dis 2019; 68:1463–71. - PubMed
    1. Verweij PE, Ananda-Rajah M, Andes D, et al. . International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat 2015:30–40. - PubMed

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