Abstract
Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management. A qPCR targeting Cunninghamella was developed a posteriori, and a retrospective analysis showed that a sample was positive more than 30 days before culture-based identification could be made.
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References
Farmakiotis D, Kontoyiannis DP. Mucormycoses. Infect Dis Clin North Am. 2016;30:143–63.
Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433–44.
Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011;17:1859–67.
Bitar D, Che D. Epidemiology of mucormycosis in metropolitan France, 1997-2010. Med Sci. 2013;29:7–12.
Millon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E, et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis. 2013;56:e95–101.
Caillot D, Valot S, Lafon I, Basmaciyan L, Chretien ML, Sautour M, et al. Is it time to include CT “Reverse Halo Sign” and qPCR targeting mucorales in serum to EORTC-MSG criteria for the diagnosis of pulmonary mucormycosis in leukemia patients? Open Forum Infect Dis. 2016;3:ofw190.
Bourcier J, Heudes PM, Morio F, Gastinne T, Chevallier P, Rialland-Battisti F, et al. Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016). Mycoses. 2017;60:526–33.
Springer J, Lackner M, Ensinger C, Risslegger B, Morton CO, Nachbaur D, et al. Clinical evaluation of a Mucorales-specific real-time PCR assay in tissue and serum samples. J Med Microbiol. 2016;65:1414–21.
Petraitis V, Petraitiene R, Antachopoulos C, Hughes JE, Cotton MP, Kasai M, et al. Increased virulence of Cunninghamella bertholletiae in experimental pulmonary mucormycosis: correlation with circulating molecular biomarkers, sporangiospore germination and hyphal metabolism. Med Mycol. 2013;51:72–82.
Bellanger AP, Millon L, Berceanu A, Grenouillet F, Grenouillet FE, Larosa F, et al. Combining Aspergillus mitochondrial and ribosomal QPCR, in addition to galactomannan assay, for early diagnosis of invasive aspergillosis in hematology patients. Med Mycol. 2015;53:760–4.
Strati P, Wierda W, Burger J, Ferrajoli A, Tam C, Lerner S, et al. Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: analysis of persistent and new-onset cytopenia. Cancer. 2013;119:3805–11.
Acknowledgements
This work was supported by a grant from the French Ministry of Health (PHRC (Projet Hospitalier de Recherche Clinique) national-ModiMucor 2014-A00580-47). We thank the National Reference Center of Invasive Mycosis and Antifungal Molecular Mycology Unit (CNRMA), Pasteur Institute, Paris, France. We thank Pamela Albert for her editorial assistance.
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Bellanger, AP., Berceanu, A., Rocchi, S. et al. Development of a quantitative PCR detecting Cunninghamella bertholletiae to help in diagnosing this rare and aggressive mucormycosis. Bone Marrow Transplant 53, 1180–1183 (2018). https://doi.org/10.1038/s41409-018-0194-5
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DOI: https://doi.org/10.1038/s41409-018-0194-5
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