MALDI-TOF MS-based evaluation for azole-susceptibility testing of Aspergillus fumigatus over reference broth microdilution method

Abstract INTRODUCTION: Azole resistance in Aspergillus fumigatus constitutes an emergency health problem, and the rapid and reliable characterization of this pathogen is essential to guide the appropriate antifungal therapy, techniques based on mass spectrometry, in these cases, could reduce the time of diagnosis in comparison to traditional methods used in hospital routine, with this we intend to establish a protocol to determine the antifungal susceptibility by MALDI TOF MS of Aspergillus fumigatus isolates and correlated with the CLSI guideline. METHODS: Sixteen Aspergillus fumigatus stored at the URM Culture Collection (Brazil) and another at Nantes University (France) were evaluated by the microdilution method in reference broth against itraconazole and voriconazole and the MALDI-TOF MS was used to identify the minimum concentration of change of the protein profile after exposure to the antifungal, the spectra obtained against each concentration were applied to generate composite correlation index (CCI) matrices for each filamentous isolate individually and used to generate heat maps and virtual gel. RESULTS: In this work, the minimum inhibitory concentration by CLSI and the minimum profile change concentration by MALDI-TOF, showed an agreement of 88.2% and 82.4% for itraconazole and voriconazole, respectively. CONCLUSIONS: MALDI-TOF MS is able to determine the cutoff point of susceptibility for Aspergillus fumigatus and allows to predict the best choice of antifungal for patients with invasive aspergillosis.