TY - JOUR
T1 - Clinical Impact of Polymerase Chain Reaction-based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis
T2 - A Prospective Multicenter Study
AU - Huygens, Sammy
AU - Dunbar, Albert
AU - Buil, Jochem B.
AU - Klaassen, Corne H. W.
AU - Verweij, Paul E.
AU - van Dijk, Karin
AU - de Jonge, Nick
AU - Janssen, Jeroen J. W. M.
AU - van der Velden, Walter J. F. M.
AU - Biemond, Bart J.
AU - Bart, Aldert
AU - Bruns, Anke H. W.
AU - Haas, Pieter-Jan A.
AU - Demandt, Astrid M. P.
AU - Oudhuis, Guy
AU - von dem Borne, Peter
AU - van der Beek, Martha T.
AU - Klein, Saskia K.
AU - Godschalk, Peggy
AU - Span, Lambert F. R.
AU - Postma, Douwe F.
AU - Kampinga, Greetje A.
AU - Maertens, Johan
AU - Lagrou, Katrien
AU - Mercier, Toine
AU - Moors, Ine
AU - Boelens, Jerina
AU - Selleslag, Dominik
AU - Reynders, Marijke
AU - Zandijk, Willemien
AU - Doorduijn, Jeanette K.
AU - Cornelissen, Jan J.
AU - Schauwvlieghe, Alexander F. A. D.
AU - Rijnders, Bart J. A.
PY - 2023/7/5
Y1 - 2023/7/5
N2 - 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).
AB - 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).
KW - invasive aspergillosis
KW - azole resistance
KW - Aspergillus PCR
KW - clinical impact
KW - BRONCHOALVEOLAR LAVAGE
KW - FUMIGATUS
KW - VORICONAZOLE
KW - VALIDATION
U2 - 10.1093/cid/ciad141
DO - 10.1093/cid/ciad141
M3 - Article
C2 - 36905147
SN - 1058-4838
VL - 77
SP - 38
EP - 45
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -