COMBINATION OF INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma.

Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis.

Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %.

Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009).

1. Leventakos K., Lewis R., Kontoyiannis D. Fungal infections in leukemia patients: how do we prevent and treat them. Clin Infect Dis 2010;50(3):405–15. DOI: 10.1086/649879. PMID: 20047485.

2. Imai Y., Adachi Y., Kimura T. et al. An autopsy case of pulmonary fissure induced by zygomycosis. Int J Gen Med 2013;6:575–9. DOI: 10.2147/ijgm.s44701. PMID: 23874118.

3. Skiada A., Lanternier F., Groll A.H. et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica 2013;98(4):492–504. DOI: 10.3324/haematol.2012.065110. PMID: 22983580.

4. De Pauw B., Walsh T.J., Donnelly J.P. 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(12):1813–21. DOI: 10.1086/588660. PMID: 18462102.

5. Baddley J.W. Clinical risk factors for invasive aspergillosis. Med Mycol 2011;49(Suppl. l):7–12. DOI: 10.3109/13693786.2010.505204. PMID: 20718606.

6. Petrikkos G., Skiada A., Lortholary O. et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54(Suppl. 1):23–34. DOI: 10.1093/cid/cir866. PMID: 22247442.

7. Lanternier F., Dannaoui E., Morizot G. et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis 2012; 54(Suppl 1):35–43. DOI: 10.1093/cid/cir880. PMID: 22247443.

8. Skiada A., Pagano L., Groll A. 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(12):1859–67. DOI: 10.1111/j.1469–0691.2010.03456.x. PMID: 21199154.

9. Klimko N.N., Khostelidi S.N., Volkova A.G. et al. Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia. Mycoses 2014;57(Suppl. 3):91–6. DOI: 10.1111/myc.12247. PMID: 25187314.

10. Saegeman V., Maertens J., Ectors N. et al. Epidemiology of mucormycosis: review of 18 cases in a tertiary care hospital. Med Mycol 2010;48(2):245–54. DOI: 10.1080/13693780903059477. PMID: 19568978.

11. Климко Н.Н., Шадривова О.В., Хостелиди С.Н. и др. Инвазивный аспергиллез: результаты многоцентрового исследования. Онкогематология 2014;2:13–9. [Klimko N.N., Schadrivova O.V., Khostelidi S.N. et al. Invasive aspergillosis: results of multicenter study. Onkogematologiya = Oncohematology 2014;2:13–9. (In Russ.)]. DOI: 10.17650/1818-8346-2014-9-2-13-19.

12. Ruhnke M., Bohme A., Buchheidt D. Diagnosis of invasive fungal infections in hematology and oncology – guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO). Ann Oncol 2012;23(4):823–33. DOI: 10.1093/annonc/mdr407. PMID: 21948809.

13. Волкова А.Г., Попова М.О., Екушев К.А. и др. Роль бронхоскопии в диагностике инвазивного аспергиллеза легких у детей после трансплантации гемопоэтических стволовых клеток. Российский журнал детской гематологии и онкологии 2015;2:72–6. [Volkova A.G., Popov M.O., Ekushev K.A. et al. The role of bronchoscopy in diagnosis invasive pulmonary aspergillosis in children after hematopoietic stem cell transplantation. Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology 2015;2:72–6. (In Russ.)]. DOI: 10.17650/2311-1267-2015-2-2-72-76.

14. Климко Н.Н., Хостелиди С.Н., Шадривова О.В. и др. Инвазивный мукормикоз у онкогематологических больных (результаты проспективного исследования). Онкогематология 2017;2(12):14–22. [Klimko N.N., Khostelidi S.N., Shadrivova O.V. et al. Mucormycosis in oncohematology patients (results of the prospective study). Onkogematologiya = Oncohematology 2017;2(12):14–22. (In Russ.)]. DOI: 10.17650/1818-8346-2017-12-2-14-22.

15. Tissot F., Agrawal S., Pagano L. et al. ECIL-6 guidelines for the treatmen of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102(3):433–44. DOI: 10.3324/haematol.2016.152900. PMID: 28011902.

16. Диагностика и лечение микозов в отделениях реанимации и интенсивной терапии: Российские рекомендации. Отв. ред. Н.Н. Климко. 2-е изд. доп. и перераб. М.: Фармтек, 2015. [Diagnosis and treatment of mycoses in intensive care units. Russian recommendations. Ed.N. N. Klimko. Moscow: Farmtek, 2015. (In Russ.)].