Combination of invasive aspergillosis and mucormycosis in hematological patients

O Shadrivova1, S Khostelidi1, Y Borzova1, E Desyatik1, A Volkova2, M Popova2, O Uspenskaya3, O Ruzhinskaya3, T Shneyder3, T Bogomolova1, S Ignatyeva1, L Zubarovskaya2, B Afanasyev2, N Klimko1

Author address: 

1I.Mechnikov North-Western State Medical University, Saint Petersburg, Russia 2I.Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia 3Leningrad Regional Clinical Hospital, Saint Petersburg, Russia

Abstract: 

Purpose: To analyze demographic parameters, underlying diseases, etiology, treatment and survival rate of hematological patients with combination of invasive aspergillosis (IA) and mucormycosis in St. Petersburg, Russia.

Methods: The prospective study was conducted during the period 2007-2017 yy. Diagnosis of IA and mucormycosis was made according to EORTC/MSG criteria (2008). Species identification of Aspergillus and mycormycetes was confirmed by sequencing of beta-tubulin and ITS/D1-D2 fragments of fungal ribosomal DNA, respectively.

Results: In a prospective multicenter study in 2007-2017 yy. were included 512 oncohematological patients with IA, and 29 (5%) of them had a combination of IA with mucormycosis. The median age of patients with IA and mucormycosis was 31 years (range 5-65), male and female ratio 2:1, adults were 83%. Main underlying conditions were: acute lymphoblastic leukemia – 32%, acute myeloid leukemia – 25%, acute leukemia – 7%, non-Hodgkin's lymphoma - 14%, Hodgkin's lymphoma – 7%, chronic myeloid leukemia – 3%, chronic lymphoblastic leukemia – 3%, myelofibrosis -3%, neuroblastoma -3%, aplastic anemia - 3% . We identified that the combination of IA and mucormycosis significantly often develops in patients after allogeneic transplants of hematopoietic stem cells (allo-HSCT) (52%, p = 0.001).

Aspergillus spp. were isolated from 51% of patients. The main agents of IA were A. fumigatus - 55%, A. niger - 17%, A. flavus - 17%, and A. nidulans - 11%. Test «Platelia Aspergillus EIA» (Bio-Rad) was positive in 62% of patients. Diagnosis of mucormycosis was confirmed by histology and direct microscopy of biopsy samples in all patients. Cultures of clinical materials were positive in 69% cases: Rhizopus spp. (45%), Lichtheimia corymbifera (20%), Rhizomucor spp. (10%), Rhizomucor pusillus (10%), Mucor sp. (10%), Rhizopus stoloniter (5%).

The main sites of infection were lungs (76%), sinuses (17%), central nervous system (10%), more then two organs were affected in 45% patients. Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24%, p = 0,008), CT-signs - lesions with cavities (38%), hydrothorax (29%), and a "reverse halo" symptom (17%).

Antifungal therapy was used in 76% patients: posaconazole – 62%, amphotericin B deoxycholate – 50%, caspofungin – 41%, amphotericin B lipid complex – 41%. Combination therapy was used for 41% patients. Duration of antifungal therapy was 3 - 236 days (median - 45). Surgical treatment was used in 34% patients. Overall survival at 12 weeks was 38%. An unfavorable prognosis factor was dissemination of mycotic infections (p = 0.009).

Conclusion: The main underlying disease in hematological patients with IA and mucormycosis was acute leukemia (64%). The main etiology agents were A. fumigatus (55%) and Rhizopus spp. (45%). Antifungal therapy received 76% patients, surgery – 34%. Twelve weeks overall survival was 38%. Disseminated mycosiswas an unfavorable prognosis factor.

2018

Full conference title: 

The 8th Advances Against Aspergillus, Lisbon Conference Center, Lisbon, Portugal
    • AAA 8th (2018)