Combination of invasive aspergillosis and mucormycosis in children: a case report and the results of a multicenter study

Objective. To study risk factors, etiology, clinical signs and treatment outcomes of invasive aspergillosis (IA) and mucormycosis combination (IAM) in children. Materials and Methods. A retrospective review of Saint-Petersburg register (1998–2021) of patients with IA was done and children with IAM were included. EORTC/MSGERG 2019 criteria were used for diagnosing and treatment results evaluation of invasive mycosis. We presented a clinical case of IAM in a child with acute lymphoblastic leukemia relapse. Results. A total of 12 children with IAM were included. They accounted 8% of all pediatric patients with invasive aspergillosis (n = 152). IAM was diagnosed in children with hematological malignancies and solid tumors from 4 to 16 years (median age – 11.5 years), mostly in girls (83%). Main risk factors of IAM were prolonged lymphopenia (75%, median 22 days) and neutropenia (67%, median 30 days) due to chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. The predominant etiological agents of IA were Aspergillus niger (33%), A. nidulans (33%) and A. fumigatus (17%), of mucormycosis – Lichtheimia corymbifera (50%) and Rhizomucor spp. (50%). Based on EORTC/MSGERG 2019 criteria, «proven» mucormycosis was diagnosed in 83% of patients, «probable» – in 17%. «Probable» IA was found in 100% of patients. The most common clinical sites of IAM were the lungs (75%) and paranasal sinuses (43%), multifocal involvement was revealed in 33% of patients. Mucormycosis developed during antifungal therapy of IA in 83% of patients. Antifungal therapy of mucormycosis received 75% of patients (amphotericin B lipid complex – 89%, posaconazole – 78%, caspofungin – 33%), combined antifungal therapy – 33%, surgery – 50%; combination of surgical and antifungal treatment was used in 42% of patients. The overall 12-week survival was 77.8%. The use of combined surgical and antifungal treatment significantly improved the survival of children with IAM (p = 0.023). Conclusions. Mucormycosis was diagnosed in 8% of children with IA. IAM developed mostly in patients with hematological malignancies (83%), prolonged lymphopenia (75%) and neutropenia (67%) against the background of chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. In 83% of patients mucormycosis was diagnosed during antifungal therapy for IA. The development of IAM increased overall 12-week mortality (50%). The combination of antifungal therapy with surgical treatment significantly improved prognosis of IAM (p = 0.023).

[1]  P. Escribano,et al.  Correction: Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates , 2020, PloS one.

[2]  A. Veselov The tablet formulation of posaconazole: clinical pharmacology and the use in patients with hematologic malignancies , 2020 .

[3]  C. Jung,et al.  Antifungal prophylaxis with posaconazole tablet and oral suspension in patients with haematologic malignancy: Therapeutic drug monitoring, efficacy and risk factors for the suboptimal level , 2020, Mycoses.

[4]  J. Perfect,et al.  Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  E. Roilides,et al.  Escmid-ecmm guideline: diagnosis and management of invasive aspergillosis in neonates and children. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[6]  A. Chakrabarti,et al.  PS1284 GLOBAL GUIDELINE FOR THE DIAGNOSIS AND MANAGEMENT OF MUCORMYCOSIS: AN INITIATIVE OF THE ECMM IN COOPERATION WITH THE MSG ERC , 2019, HemaSphere.

[7]  A. Attarbaschi,et al.  Incidence and Outcome of Invasive Fungal Diseases in Children With Hematological Malignancies and/or Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Study , 2019, Front. Microbiol..

[8]  B. Afanasyev,et al.  Contrasts between mucormycosis and aspergillosis in oncohematological patients. , 2019, Medical mycology.

[9]  J. Donnelly,et al.  New Concepts in Diagnostics for Invasive Mycoses: Non-Culture-Based Methodologies , 2019, Journal of fungi.

[10]  B. Phillips,et al.  Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review , 2018, Journal of the Pediatric Infectious Diseases Society.

[11]  Л. С. Зубаровская,et al.  Сочетание инвазивного аспергиллеза и мукормикоза у онкогематологических больных , 2018 .

[12]  G. Ottaviani,et al.  Combined Orofacial Aspergillosis and Mucormycosis: Fatal Complication of a Recurrent Paediatric Glioma—Case Report and Review of Literature , 2016, Mycopathologia.

[13]  Sung‐Han Kim,et al.  Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[14]  A. Guarascio,et al.  Review of the New Delayed‐Release Oral Tablet and Intravenous Dosage Forms of Posaconazole , 2015, Pharmacotherapy.

[15]  A. Kolbin,et al.  Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia , 2014, Mycoses.

[16]  L. Pagano,et al.  SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients , 2013, Infection.

[17]  S. Alexander,et al.  Antifungal prophylaxis in pediatric hematology/oncology: New choices & new data , 2012, Pediatric blood & cancer.

[18]  M. Godoy,et al.  Reversed halo sign: high-resolution CT scan findings in 79 patients. , 2012, Chest.

[19]  C. Elie,et al.  A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007). , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  P. Hamal,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. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[21]  S. Y. Park,et al.  Clinical and radiological features of invasive pulmonary aspergillosis in transplant recipients and neutropenic patients , 2010, Transplant infectious disease : an official journal of the Transplantation Society.

[22]  J. Sivik,et al.  Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up , 2008, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[23]  G. Socié,et al.  Breakthrough Rhizopus infection on posaconazole prophylaxis following allogeneic stem cell transplantation , 2008, Bone Marrow Transplantation.

[24]  J. Mehta,et al.  Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy , 2007, Bone Marrow Transplantation.

[25]  D. Day,et al.  Pulmonary fungal infections after bone marrow transplantation , 2006, Pediatric Radiology.

[26]  W. Leisenring,et al.  Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  B. Gibson,et al.  Mixed pulmonary fungal infection with Aspergillus fumigatus and Absidia corymbifera in a patient with relapsed acute myeloid leukaemia , 2005, British journal of haematology.

[28]  F. Marty,et al.  Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. , 2004, The New England journal of medicine.

[29]  M. Sande,et al.  Simultaneous disseminated aspergillosis and zygomycosis in a leukemic patient. , 1979, Southern medical journal.