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VIPcheck: an agar-based assay for Aspergillus fumigatus azole susceptibility screening

November 28 2017

With the rise of azole resistance in Aspergillus fumigatus, susceptibility testing is more important than ever when choosing an antifungal treatment. Two reference methods based on broth microdilution are available (CLSI M38-A2 and EUCAST E.Def 9.3), but these are technically challenging and therefore not available in most routine microbiology labs, and sending samples to a mycology reference lab incurs a delay. A commercial agar-based assay would allow routine labs to rapidly screen at-risk patients and begin antifungal treatment while awaiting the results of external MIC testing. This year, two evaluations of such an assay were published in the Journal of Antimicrobial Chemotherapy. VIPcheckTM compares the growth of clinical isolates of A. fumigatus in control medium against their growth in the presence of either Voriconazole, Itraconazole or Posaconazole, giving results after 24-48 hours. Isavuconazole is not included in the assay due to a high degree of cross-resistance to voriconazole.

VIPcheckTM is being commercialised by a group in Nijmegen (Netherlands) and is currently available for research purposes only.

The Dutch group who designed VIPcheckTM tested it on a collection of well-characterised clinical isolates of A. fumigatus with a diverse range of resistance genotypes . Sensitivity (92-100%) and specificity (67-100%) were both high, and the test could be used easily by non-expert technicians.

 

A multicentre study reported a sensitivity and specificity of 99%. The only isolate to be mis-classified was a borderline resistant strain harbouring the M220T mutation. When a mixture of WT (80%) and azole resistant (20%) strains were tested, the sensitivity was still high, suggesting that the assay would be useful for mixed infections.

 

Additionally, a Belgian group used VIPcheckTM to test samples from 109 hospitalized patients (a mixture of cystic fibrosis, COPD and transplant patients), giving an overall prevalence of azole resistance of 12.8%. They suggest that the assay could be done in parallel with the AsperGenius real-time PCR assay in high-risk settings.