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- Title
PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay® in 201 patients with haematological disease suspected for invasive aspergillosis.
- Authors
Chong, G. M.; van der Beek, M. T.; von dem Borne, P. A.; Boelens, J.; Steel, E.; Kampinga, G. A.; Span, L. F. R.; Lagrou, K.; Maertens, J. A.; Dingemans, G. J. H.; Gaajetaan, G. R.; van Tegelen, D. W. E.; Cornelissen, J. J.; Vonk, A. G.; Rijnders, B. J. A.
- Abstract
<bold>Objectives: </bold>In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius® multiplex real-time PCR assay identifies clinically relevant Aspergillus species and four resistance-associated mutations (RAMs; TR34/L98H/T289A/Y121F) in the Cyp51A gene. This multicentre study evaluated the diagnostic performance of this assay on bronchoalveolar lavage (BAL) fluid and correlated the presence of RAMs with azole treatment failure and mortality.<bold>Methods: </bold>Stored BAL samples from patients with haematological diseases with suspected IA were used. BAL samples that were galactomannan/culture positive were considered positive controls for the presence of Aspergillus. Azole treatment failure and 6 week mortality were compared in patients with and without RAMs that had received ≥5 days of voriconazole monotherapy.<bold>Results: </bold>Two hundred and one patients each contributed one BAL sample, of which 88 were positive controls and 113 were negative controls. The optimal cycle threshold cut-off value for the Aspergillus species PCR was <38. With this cut-off, the PCR was positive in 74/88 positive controls. The sensitivity, specificity, positive predictive value and negative predictive value were 84%, 80%, 76% and 87%, respectively. 32/74 BAL samples were culture negative. Azole treatment failure was observed in 6/8 patients with a RAM compared with 12/45 patients without RAMs (P = 0.01). Six week mortality was 2.7 times higher in patients with RAMs (50.0% versus 18.6%; P = 0.07).<bold>Conclusions: </bold>The AsperGenius® assay had a good diagnostic performance on BAL and differentiated WT from Aspergillus fumigatus with RAMs, including in culture-negative BAL samples. Most importantly, detection of RAMs was associated with azole treatment failure.
- Subjects
ASPERGILLOSIS diagnosis; ASPERGILLOSIS treatment; BRONCHOALVEOLAR lavage; HEMATOLOGIC malignancies; PATIENT acceptance of health care; AZOLES; PATIENTS; THERAPEUTICS; ANTIFUNGAL agents; ASPERGILLUS; BLOOD diseases; BODY fluids; DRUG resistance in microorganisms; GENETIC techniques; HEMOPROTEINS; GENETIC mutation; HETEROCYCLIC compounds; POLYMERASE chain reaction; PROTEINS; PULMONARY aspergillosis; SURVIVAL analysis (Biometry); TREATMENT effectiveness; RETROSPECTIVE studies; DISEASE complications; PHARMACODYNAMICS; DIAGNOSIS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2016, Vol 71, Issue 12, p3528
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkw323