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.
J Antimicrob Chemother
; 71(12): 3528-3535, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27530755
ABSTRACT
OBJECTIVES:
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.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 (Pâ=â0.01). Six week mortality was 2.7 times higher in patients with RAMs (50.0% versus 18.6%; Pâ=â0.07).CONCLUSIONS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspergillus fumigatus
/
Proteínas Fúngicas
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Líquido da Lavagem Broncoalveolar
/
Reação em Cadeia da Polimerase
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Sistema Enzimático do Citocromo P-450
/
Farmacorresistência Fúngica
/
Aspergilose Pulmonar Invasiva
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda