Advanced search
1 file | 330.30 KB Add to list

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

Author
Organization
Abstract
Objectives: In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius (R) 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. Methods: 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. Results: 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). Conclusions: The AsperGenius (R) 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.
Keywords
HIGH-RISK PATIENTS, AZOLE RESISTANCE, ANTIFUNGAL THERAPY, CLINICAL-SAMPLES, DRUG-RESISTANCE, FLUID SAMPLES, CYP51A GENE, FUMIGATUS, INFECTIONS, DNA

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 330.30 KB

Citation

Please use this url to cite or link to this publication:

MLA
Chong, GM, MT van der Beek, PA von dem Borne, et al. “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.” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 71.12 (2016): 3528–3535. Print.
APA
Chong, G., van der Beek, M., von dem Borne, P., Boelens, J., STEEL, E., Kampinga, G., Span, L., et al. (2016). 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. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 71(12), 3528–3535.
Chicago author-date
Chong, GM, MT van der Beek, PA von dem Borne, Jerina Boelens, EVA STEEL, GA Kampinga, LFR Span, et al. 2016. “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.” Journal of Antimicrobial Chemotherapy 71 (12): 3528–3535.
Chicago author-date (all authors)
Chong, GM, MT van der Beek, PA von dem Borne, Jerina Boelens, EVA STEEL, GA Kampinga, LFR Span, K Lagrou, JA Maertens, GJH Dingemans, GR Gaajetaan, DWE van Tegelen, JJ Cornelissen, AG Vonk, and BJA Rijnders. 2016. “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.” Journal of Antimicrobial Chemotherapy 71 (12): 3528–3535.
Vancouver
1.
Chong G, van der Beek M, von dem Borne P, Boelens J, STEEL E, Kampinga G, et al. 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. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 2016;71(12):3528–35.
IEEE
[1]
G. Chong et al., “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,” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 71, no. 12, pp. 3528–3535, 2016.
@article{8509467,
  abstract     = {Objectives: In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius (R) 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. 
Methods: 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. 
Results: 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). 
Conclusions: The AsperGenius (R) 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.},
  author       = {Chong, GM and van der Beek, MT and von dem Borne, PA and Boelens, Jerina and STEEL, EVA and Kampinga, GA and Span, LFR and Lagrou, K and Maertens, JA and Dingemans, GJH and Gaajetaan, GR and van Tegelen, DWE and Cornelissen, JJ and Vonk, AG and Rijnders, BJA},
  issn         = {0305-7453},
  journal      = {JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY},
  keywords     = {HIGH-RISK PATIENTS,AZOLE RESISTANCE,ANTIFUNGAL THERAPY,CLINICAL-SAMPLES,DRUG-RESISTANCE,FLUID SAMPLES,CYP51A GENE,FUMIGATUS,INFECTIONS,DNA},
  language     = {eng},
  number       = {12},
  pages        = {3528--3535},
  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},
  url          = {http://dx.doi.org/10.1093/jac/dkw323},
  volume       = {71},
  year         = {2016},
}

Altmetric
View in Altmetric
Web of Science
Times cited: