Abstract
Background
Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI).
Methods
We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center.
Results
Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis.
Conclusions
Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.
Similar content being viewed by others
References
Bitar D, Lortholary O, Le Strat Y, Nicolau J, Coignard B, Tattevin P, et al. Population-based analysis of invasive fungal infections, France, 2001–2010. Emerg Infect Dis. 2014;20:1163–9.
Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.
Kume H, Yamazaki T, Togano T, Abe M, Tanuma H, Kawana S, Okudaira M. Epidemiology of visceral mycoses in autopsy cases in Japan: comparison of the data from 1989, 1993, 1997, 2001, 2005 and 2007 in annual of pathological autopsy cases in Japan. Med Mycol J. 2011;52:117–27.
Auberger J, Lass-Flörl C, Ulmer H, Nogler-Semenitz E, Clausen J, Gunsilius E, et al. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol. 2008;88:508–15.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.
Leber AL, editor. Clinical microbiology procedures handbook, USA. Washington: ASM Press; 2016.
Kurtzman CP, Robnett CJ. Identification of Clinically important ascomycetous yeasts based on nucleotide divergence in the 5′ end of the large-subunit (26S) ribosomal DNA gene. J Clin Microbiol. 1997;35(5):1216–23.
Chen YC, Eisner JD, Kattar MM, Rassoulian-Barrett SL, Lafe K, Bui U, Limaye AP, Cookson BT. Polymorphic internal transcribed spacer region 1 DNA sequences identify medically important yeasts. J Clin Microbiol. 2001;39:4042–51.
Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91:986–9.
Kurosawa M, Yonezumi M, Hashino S, et al. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol. 2012;96(6):748–57.
Lewis RE, Cahyame-Zuniga L, Leventakos K, Chamilos G, Ben-Ami R, Tamboli P, Tarrand J, Bodey GP, Luna M. Kontoyiannis DP Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study. Mycoses. 2013;56(6):638–45.
Hardak E, Fuchs E, Leskes H, Geffen Y, Zuckerman T, Oren I. Diagnostic role of polymerase chain reaction in bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in immunocompromised patients—a retrospective cohort study. Int J Infect Dis. 2019;83:20–5.
Nosari AM, et al. Invasive fungal infections in lymphoproliferative disorders: a monocentric retrospective experience. Leuk Lymphoma. 2014;55(8):1844–8.
Takaoka K, et al. A novel scoring system to predict the incidence of invasive fungal disease in salvage chemotherapies for malignant lymphoma. Ann Hematol. 2014;93(10):1637–44.
Tisi MC, et al. Invasive fungal infections in chronic lymphoproliferative disorders: a monocentric retrospective study. Haematologica. 2017;102(3):e108–11.
Kanamori H, Rutala WA, Sickbert-Bennett EE, Weber J. Review of fungal outbreaks and infection prevention in healthcare settings during construction and renovation. Clin Infect Dis. 2015;61(3):433–44.
Guarro J. Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment. Eur J Clin Microbiol Infect Dis. 2013;32(12):1491–500.
Jossi M, Ambrosioni J, Macedo-Vinas M, Garbino J. Invasive fusariosis with prolonged fungemia in a patient with acute lymphoblastic leukemia: case report and review of the literature. Int J Infect Dis. 2010;14(4):e354–6.
Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53.
Slavin M, van Hal S, Sorrell TC, Lee A, Marriott DJ, Daveson K, Kennedy K, Hajkowicz K, Halliday C, Athan E, Bak N, Cheong E, Heath CH, OrlaMorrissey C, Kidd S, Beresford R, Blyth C, Korman TM, OwenRobinson J, Meyer W, Chen SC, Australia and New Zealand Mycoses Interest Group. Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality. Clin Microbiol Infect. 2015;21(5):490.e1–10 Epub 2015 Jan 14.
Hammond SP, Marty FM, Bryar JM, DeAngelo DJ, Baden LR. Invasive fungal disease in patients treated for newly diagnosed acute leukemia. Am J Hematol. 2010;85(9):695–9.
Bow EJ. Considerations in the approach to invasive fungal infection in patients with haematological malignancies. Br J Haematol. 2008;140(2):133–52.
Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191:1350–60.
Husain S, Alexander BD, Munoz P, Avery RK, Houston S, Pruett T, et al. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis. 2003;37:221–9.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The author declares that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Handling Editor: Stephane Ranque.
Rights and permissions
About this article
Cite this article
Hardak, E., Fuchs, E., Geffen, Y. et al. Clinical Spectrum, Diagnosis and Outcome of Rare Fungal Infections in Patients with Hematological Malignancies: Experience of 15-Year Period from a Single Tertiary Medical Center. Mycopathologia 185, 347–355 (2020). https://doi.org/10.1007/s11046-020-00436-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11046-020-00436-x