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

Chong, GM; van der Beek, MT; von dem Borne, PA; Boelens, J; Steel, E; Kampinga, GA; Span, LFR; Lagrou, Katrien; Maertens, JA; Dingemans, GJH; Gaajetaan, GR; van Tegelen, DWE; Cornelissen, JJ; Vonk, AG; Rijnders, BJA

doi:10.1093/jac/dkw323

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:

Chong, GM

van der Beek, MT ; von dem Borne, PA ; Boelens, J ; Steel, E ; Kampinga, GA ; Span, LFR ; Lagrou, Katrien ; Maertens, JA ; Dingemans, GJH ; Gaajetaan, GR ; van Tegelen, DWE ; Cornelissen, JJ ; Vonk, AG ; Rijnders, BJA

Keywords:

Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, Microbiology, Pharmacology & Pharmacy, HIGH-RISK PATIENTS, AZOLE RESISTANCE, ANTIFUNGAL THERAPY, CLINICAL-SAMPLES, DRUG-RESISTANCE, FLUID SAMPLES, CYP51A GENE, FUMIGATUS, INFECTIONS, DNA, Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents, Aspergillus fumigatus, Azoles, Bronchoalveolar Lavage Fluid, Cytochrome P-450 Enzyme System, Drug Resistance, Fungal, Female, Fungal Proteins, Genotyping Techniques, Hematologic Diseases, Humans, Invasive Pulmonary Aspergillosis, Male, Middle Aged, Mutation, Polymerase Chain Reaction, Retrospective Studies, Survival Analysis, Treatment Failure, Young Adult, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, 3202 Clinical sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

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.