
Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis : a prospective multicenter study
- Author
- Sammy Huygens, Albert Dunbar, Jochem B. Buil, Corne 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. Span, Douwe F. Postma, Greetje A. Kampinga, Johan Maertens, Katrien Lagrou (UGent) , Toine Mercier, Ine Moors (UGent) , Jerina Boelens (UGent) , Dominik Selleslag, Marijke Reynders, Willemien Zandijk, Jeanette K. Doorduijn, Jan J. Cornelissen, Alexander F. A. D. Schauwvlieghe and Bart J. A. Rijnders
- Organization
- Abstract
- This prospective multicenter study showed that real-time resistance testing may limit the impact of azole resistance on mortality. An isolated positive polymerase chain reaction assay was not associated with mortality. Its place in the current EORTC/MSGERC definitions should be reconsidered. 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
- invasive aspergillosis, azole resistance, Aspergillus PCR, clinical impact, BRONCHOALVEOLAR LAVAGE, FUMIGATUS, VORICONAZOLE, VALIDATION
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HPHHYSNVS1GFD3T0AJ07HRAC
- MLA
- Huygens, Sammy, et al. “Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis : A Prospective Multicenter Study.” CLINICAL INFECTIOUS DISEASES, vol. 77, no. 1, Oxford Univ Press Inc, 2023, pp. 38–45, doi:10.1093/cid/ciad141.
- APA
- Huygens, S., Dunbar, A., Buil, J. B., Klaassen, C. H. W., Verweij, P. E., van Dijk, K., … Rijnders, B. J. A. (2023). Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis : a prospective multicenter study. CLINICAL INFECTIOUS DISEASES, 77(1), 38–45. https://doi.org/10.1093/cid/ciad141
- Chicago author-date
- Huygens, Sammy, Albert Dunbar, Jochem B. Buil, Corne H. W. Klaassen, Paul E. Verweij, Karin van Dijk, Nick de Jonge, et al. 2023. “Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis : A Prospective Multicenter Study.” CLINICAL INFECTIOUS DISEASES 77 (1): 38–45. https://doi.org/10.1093/cid/ciad141.
- Chicago author-date (all authors)
- Huygens, Sammy, Albert Dunbar, Jochem B. Buil, Corne 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. Span, Douwe 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, and Bart J. A. Rijnders. 2023. “Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis : A Prospective Multicenter Study.” CLINICAL INFECTIOUS DISEASES 77 (1): 38–45. doi:10.1093/cid/ciad141.
- Vancouver
- 1.Huygens S, Dunbar A, Buil JB, Klaassen CHW, Verweij PE, van Dijk K, et al. Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis : a prospective multicenter study. CLINICAL INFECTIOUS DISEASES. 2023;77(1):38–45.
- IEEE
- [1]S. Huygens et al., “Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis : a prospective multicenter study,” CLINICAL INFECTIOUS DISEASES, vol. 77, no. 1, pp. 38–45, 2023.
@article{01HPHHYSNVS1GFD3T0AJ07HRAC, abstract = {{This prospective multicenter study showed that real-time resistance testing may limit the impact of azole resistance on mortality. An isolated positive polymerase chain reaction assay was not associated with mortality. Its place in the current EORTC/MSGERC definitions should be reconsidered. 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).}}, author = {{Huygens, Sammy and Dunbar, Albert and Buil, Jochem B. and Klaassen, Corne H. W. and Verweij, Paul E. and van Dijk, Karin and de Jonge, Nick and Janssen, Jeroen J. W. M. and van der Velden, Walter J. F. M. and Biemond, Bart J. and Bart, Aldert and Bruns, Anke H. W. and Haas, Pieter-Jan A. and Demandt, Astrid M. P. and Oudhuis, Guy and von dem Borne, Peter and van der Beek, Martha T. and Klein, Saskia K. and Godschalk, Peggy and Span, Lambert F. R. and Postma, Douwe F. and Kampinga, Greetje A. and Maertens, Johan and Lagrou, Katrien and Mercier, Toine and Moors, Ine and Boelens, Jerina and Selleslag, Dominik and Reynders, Marijke and Zandijk, Willemien and Doorduijn, Jeanette K. and Cornelissen, Jan J. and Schauwvlieghe, Alexander F. A. D. and Rijnders, Bart J. A.}}, issn = {{1058-4838}}, journal = {{CLINICAL INFECTIOUS DISEASES}}, keywords = {{invasive aspergillosis,azole resistance,Aspergillus PCR,clinical impact,BRONCHOALVEOLAR LAVAGE,FUMIGATUS,VORICONAZOLE,VALIDATION}}, language = {{eng}}, number = {{1}}, pages = {{38--45}}, publisher = {{Oxford Univ Press Inc}}, title = {{Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis : a prospective multicenter study}}, url = {{http://doi.org/10.1093/cid/ciad141}}, volume = {{77}}, year = {{2023}}, }
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