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

被引：40

作者：

Huygens, Sammy ^{[1
,2
]}

Dunbar, Albert ^{[1
,2
]}

Buil, Jochem B. ^{[3
]}

Klaassen, Corne H. W. ^{[4
]}

Verweij, Paul E. ^{[3
]}

van Dijk, Karin ^{[5
]}

de Jonge, Nick ^{[6
]}

Janssen, Jeroen J. W. M. ^{[6
]}

van der Velden, Walter J. F. M. ^{[7
]}

Biemond, Bart J. ^{[8
]}

Bart, Aldert ^{[9
]}

Bruns, Anke H. W. ^{[10
]}

Haas, Pieter-Jan A. ^{[11
]}

Demandt, Astrid M. P. ^{[12
]}

Oudhuis, Guy ^{[13
]}

von dem Borne, Peter ^{[14
]}

van der Beek, Martha T. ^{[15
]}

Klein, Saskia K. ^{[16
,17
]}

Godschalk, Peggy ^{[18
]}

Span, Lambert F. R. ^{[17
]}

Postma, Douwe F. ^{[19
]}

Kampinga, Greetje A. ^{[20
]}

Maertens, Johan ^{[21
,22
]}

Lagrou, Katrien ^{[22
,23
,24
]}

Mercier, Toine ^{[22
]}

Moors, Ine ^{[25
]}

Boelens, Jerina ^{[26
]}

Selleslag, Dominik ^{[27
]}

Reynders, Marijke ^{[28
]}

Zandijk, Willemien ^{[4
]}

Doorduijn, Jeanette K. ^{[29
]}

Cornelissen, Jan J. ^{[29
]}

Schauwvlieghe, Alexander F. A. D. ^{[27
]}

Rijnders, Bart J. A. ^{[1
,2
]}

机构：

[1] Erasmus MC, Univ Med Ctr, Infect Dis Sect, Dept Internal Med, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands

[2] Erasmus MC, Univ Med Ctr, Dept Med Microbiol & Infect Dis, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands

[3] Radboud Univ Ctr, Dept Med Microbiol, Nijmegen, Netherlands

[4] Erasmus MC, Univ Med Ctr, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands

[5] Amsterdam Univ Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands

[6] Amsterdam Univ Med Ctr, Dept Hematol, Amsterdam, Netherlands

[7] Radboud Univ Ctr, Dept Hematol, Nijmegen, Netherlands

[8] Amsterdam Univ Med Ctr, Dept Hematol, Amsterdam, Netherlands

[9] Amsterdam Univ Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands

[10] Univ Med Ctr Utrecht, Dept Internal Med, Infect Dis, Utrecht, Netherlands

[11] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands

[12] Maastricht Univ Med Ctr, Dept Hematol, Maastricht, Netherlands

[13] Maastricht Univ Med Ctr, Dept Med Microbiol, Maastricht, Netherlands

[14] Leiden Univ Med Ctr, Dept Med Microbiol, Leiden, Netherlands

[15] Leiden Univ Med Ctr, Dept Hematol, Leiden, Netherlands

[16] Meander Med Ctr, Dept Hematol, Amersfoort, Netherlands

[17] Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands

[18] Meander Med Ctr, Dept Med Microbiol, Amersfoort, Netherlands

[19] Univ Med Ctr Groningen, Dept Internal Med & Infect Dis, Groningen, Netherlands

[20] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol, Groningen, Netherlands

[21] Univ Hosp Leuven, Dept Hematol, Leuven, Belgium

[22] Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Leuven, Belgium

[23] Univ Hosp Leuven, Dept Lab Med, Leuven, Belgium

[24] Univ Hosp Leuven, Natl Reference Ctr, Leuven, Belgium

[25] Ghent Univ Hosp, Dept Hematol, Ghent, Belgium

[26] Ghent Univ Hosp, Dept Med Microbiol, Ghent, Belgium

[27] AZ St Jan Brugge Oostende Hosp, Dept Hematol, Brugge, Belgium

[28] AZ St Jan Brugge Oostende Hosp, Dept Lab Med, Med Microbiol, Brugge, Belgium

[29] Erasmus MC, Dept Hematol, Rotterdam, Netherlands

来源：

CLINICAL INFECTIOUS DISEASES | 2023年 / 77卷 / 01期

关键词：

invasive aspergillosis; azole resistance; Aspergillus PCR; clinical impact; BRONCHOALVEOLAR LAVAGE; FUMIGATUS; VORICONAZOLE; VALIDATION;

D O I：

10.1093/cid/ciad141

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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).

引用

页码：38 / 45

页数：8

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