The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis

Cruciani, M., White, P. L., Mengoli, C., Löffler, J., Morton, C. O., Klingspor, L., Buchheidt, D., Maertens, J., Heinz, W. J., Rogers, T. R., Weinbergerova, B., Warris, A., Lockhart, D. E. A., Jones, B., Cordonnier, C., Donnelly, J. P., Barnes, R. A., Klingspor, L., Buchheidt, D., Maertens, J., Heinz, W. J., Rogers, T. R., Weinbergerova, B., Warris, A., Lockhart, D. E. A., Jones, B., Cordonnier, C., Donnelly, J. P. and Barnes, R. A. 2021. The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis. Journal of Antimicrobial Chemotherapy 76 (3) , pp. 635-638. 10.1093/jac/dkaa498

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Abstract

Background The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. Objectives To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). Methods As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. Results In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)]. Conclusions Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Oxford University Press
ISSN:	0305-7453
Date of First Compliant Deposit:	26 January 2022
Date of Acceptance:	29 October 2020
Last Modified:	09 Nov 2023 11:31
URI:	https://orca.cardiff.ac.uk/id/eprint/146985

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