Fungal infections of the central nervous system and paranasal sinuses in onco‐haematologic patients. Epidemiological study reporting the diagnostic‐therapeutic approach and outcome in 89 cases

Abstract

Summary Invasive fungal infections (IFI) of the Central Nervous System (IFI‐CNS) and Paranasal Sinuses (IFI‐PS) are rare, life‐threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI‐CNS (71/89) and IFI‐PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5‐79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI‐CNS, and a sinus biopsy was performed in 56% of IFI‐PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI‐CNS (30/71), and it was positive in 67%. Eighty‐four pts received a first‐line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5‐835). A surgical intervention was performed in 26% of cases but only 10% of IFI‐CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1‐year overall survival was 32% without significant differences between IFI‐CNS and IFI‐PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI‐CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

The Neurotropic Black Yeast Exophiala dermatitidis Induces Neurocytotoxicity in Neuroblastoma Cells and Progressive Cell Death

“…Fungi have also been associated with other neurological diseases. Recently, an increasing number of opportunistic mycoses of the central nervous system (CNS) has been reported in healthy individuals and, in particular, in patients with sepsis, prolonged ventilation, oncological therapies, organ transplantation, overuse of antibiotics, HIV patients, and others [41,60]. Opportunistic mycoses of CNS are associated with higher morbidity and mortality [61,62] owing to pathogenic fungi such as Cryptococcus neoformans, which are able to cross the otherwise prohibitive blood-brain barrier [41,63].…”

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…Patients with aspergillosis within the CNS typically present with focal neurological signs such as pareses or seizures. Overall mortality is still high reaching 69% (with IFD‐attributable mortality 33%) in a recent study from Italy 115 . Comparable studies regarding drug treatment of CNS aspergillosis do not exist, but D‐AmB was found to be not effective 116 .…”

“…CNS: CNS infections caused by Candida spp. are extremely rare in adult patients with haematological malignancies 115,170 . Classically, patient groups at risk are (a) very low birth weight infants and (b) patients following neurosurgical interventions 171 .…”

Fungi as causative agents of healthcare-associated infections

“…(67%), następnie przestawiciele Mucorales (28%) oraz Fusarium sp. Połowa przypadków była ograniczona do zatok, a druga połowa miała postać rozsianą [30].…”

“…Wśród czynników etiologicznych dominował Aspergillus sp. (70%), rzadziej stwierdzano rodzaje z rzędu Mucorales (22%), Cryptococcus (4%) i Fusarium (2%) [30]. W 2012 r. wybuchła w USA największa zarejestrowana epidemia zakażeń związanych z zewnątrzoponowymi i dostawowymi iniekcjami octanu metyloprednizolonu (MPA) zanieczyszczonego pleśnią Exserohilum rostratum i kilkoma innymi mikroorganizmami.…”