Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial.

Background: Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis.
Methods: We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus.
Results: The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0-9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, -2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03-.73], P = .02).
Conclusions: Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR.
Competing Interests: Potential conflicts of interests. L. M. reports personal fees outside the submitted work and travel grants from Gilead and Pfizer. S. B. reports personal fees outside the submitted work and travel grants from Gilead. F. L. reports personal fees from Airnspace, Gilead, and F2G outside the submitted work. A. A. reports personal fees form Gilead and Pfizer outside the submitted work, consulting fees from Pfizer for serving on an Advisory Board; travel grants from Gilead and Pfizer; and patent licensed for Pneumocystis PCR and patent issued for Histoplasma PCR. F. D. reports travel grants from Pfizer to attend Trend in Medical Mycology congress, Aberdeen, 2021 and is Vice President for French Society of Medical Mycology. R. H. reports research grant from Gilead, personal fees form Gilead and Pfizer outside the submitted work, and travel grants from Gilead and Pfizer. A. P. B. reports support for attending meetings and/or travel from Gilead. BD reports fees for travel and as a speaker at 2 national congresses in 2021 from Gilead and consultancy fees at an expert meeting planned in 01/2022 from Pfizer. F. B. reports consulting fees, payment or honoraria, and support for attending meetings and/or travel from Gilead and support for attending meetings and/or travel from Pfizer and leadership or fiduciary role from the Society of French Medical Mycology. S. B. reports honorarium from Gilead to attend an educational workshop and support for attending meetings and/or travel from Gilead travel grant for TIMM congress Aberdeen UK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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