RT PCR can help in Early Detection of Triazole-Resistant Aspergillosis

Invasive aspergillosis (IA) caused by triazole-resistant Aspergillus fumigatus has long been associated with high mortality rates. However, a prospective study by Sammy Huygens and peers demonstrated the potential clinical value of the AsperGenius polymerase chain reaction (PCR) assay in detecting azole resistance and initiating appropriate therapy sooner. The findings were published in Clinical Infectious Diseases.

The study, which focused on hematology patients, evaluated the efficacy of the PCR assay in diagnosing IA. Computed tomography scans were used to identify pulmonary infiltrates, and bronchoalveolar fluid (BALf) samples were collected for analysis. The primary objective was to determine antifungal treatment failure in patients with azole-resistant IA.

Out of the 323 patients enrolled, complete mycological and radiological data were available for 276 (94%) individuals. Among them, probable IA was diagnosed in 99 patients (36%). Adequate BALf samples were obtained from 293 patients (91%) for PCR testing. Aspergillus DNA was detected in 116 samples (40%), with A. fumigatus DNA found in 89 samples (30%). The resistance PCR was conclusive in 58 cases (65%), and resistance was detected in 8 of these samples (14%). Interestingly, two patients exhibited mixed infections with both azole-susceptible and azole-resistant strains. Among the remaining six patients, one experienced treatment failure.

The study's findings suggest that galactomannan positivity, a marker of IA, was significantly associated with mortality. In contrast, an isolated positive Aspergillus PCR on BALf did not demonstrate a clear clinical impact. These results indicate that real-time PCR-based resistance testing may play a crucial role in limiting the adverse effects of triazole resistance in IA patients.

The researchers also highlight the need for further clarification regarding the interpretation of the PCR criterion for BALf, as specified by the European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC). They suggest that additional parameters, such as a minimum cycle threshold value and multiple PCR-positive BALf samples, could enhance the accuracy and reliability of the assay.

Source:

Huygens, S., Dunbar, A., Buil, J. B., Klaassen, C. H. W., Verweij, P. E., van Dijk, K., de Jonge, N., Janssen, J. J. W. M., van der Velden, W. J. F. M., Biemond, B. J., Klein, S. K., Godschalk, P., … Rijnders, B. J. A. (2023). Clinical Impact of Polymerase Chain Reaction–Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study. In Clinical Infectious Diseases. Oxford University Press (OUP). https://doi.org/10.1093/cid/ciad141