Advances in the diagnosis and treatment of fungal infections of the CNS

Schwartz, Stefan; Kontoyiannis, Dimitrios P.; Harrison, Thomas S.; Ruhnke, Markus

doi:10.1016/s1474-4422(18)30030-9

Cited by 102 publications

(125 citation statements)

References 95 publications

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“…Although 74% of patients were neutropenic, severe neutropenia (PMN <500/mmc) has been documented in less than 50% of cases at the time of diagnosis of IFIs. This confirms that, in addition to neutropenia, other factors, such as the active state of the underlying haematological disease and the degree of patient's immunodepression, play an important predisposing role …”

Section: Discussionsupporting

confidence: 68%

“…IFIs with localisation at CNS and PS are a rare and severe infectious complication in the course of haematological diseases. The diagnosis of such infectious complications can be complex because the symptoms and signs are not specific, indirect microbiology techniques are not validated on all biological fluids (i.e, CSF), and biopsy is often difficult in patients with underlying haematological malignancies . In the cases of CNS or PS‐IFI, the antifungal treatment is frequently associated with a poor efficacy and this is due both to the poor permeability of antifungal drugs in anatomical sites (such as CNS) and to the inability, in most cases, to integrate drug therapy with surgery …”

Section: Discussionmentioning

confidence: 99%

“…In fact, in the 34 centres participating in this study, less than 1 case per centre per year was observed. With regard to the underlying haematological disease, most of the cases were observed in patients with AML and ALL or in recipients of an allogeneic SCT . In most cases, patients had an active disease at the time of the onset of IFI while few cases occurred with a haematological disease in remission or during the consolidation phase.…”

Section: Discussionmentioning

confidence: 99%

“…There is a lack of recent epidemiologic studies with a proper number of cases reporting the outcome of haematologic patients with IFI involving CNS and PS, and therefore, the most appropriate diagnostic and therapeutic approach remain to be clearly defined. In fact, in the literature, we found only case reports or small retrospective studies, more often not recent . The most frequently reported pathogens were moulds and especially Aspergillus and Mucormycetes .…”

Section: Introductionmentioning

confidence: 91%

“…In fact, in the literature, we found only case reports or small retrospective studies, more often not recent . The most frequently reported pathogens were moulds and especially Aspergillus and Mucormycetes . The therapeutic management of these infectious complications is still very complex and heterogeneous, and recent studies on the efficacy of new antimycotic drugs are limited so that there is no clear standard of care currently available.…”

Section: Introductionmentioning

confidence: 99%

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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

Candoni¹,

Климко

Busca

et al. 2019

Mycoses

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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.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Candoni¹,

Климко

Busca

et al. 2019

Mycoses

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Screening and Synthesis of Tetrazole Derivatives that Inhibit the Growth of Cryptococcus Species

et al. 2023

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Cryptococcosis has become a major health problem worldwide and caused morbidity and mortality in immunocompromised patients, especially those infected with human immunodeficiency virus (HIV). Despite the global distribution of cryptococcosis, the number and types of the available antifungals are limited, and the treatment outcomes in HIV patients are generally poor. In this study, we screened a compound library and identified one tetrazole derivative as an efficient inhibitor of Cryptococcus neoformans and Cryptococcus gattii. We further designed and synthesized a series of tetrazole derivatives and determined their structure‐activity relationship, demonstrating that tetrazole backbone‐containing compounds could be developed as novel antifungal drugs with distinct mechanisms against Cryptococcus spp. Our findings provide a starting point for novel target identification and structural optimization to develop a distinct class of therapeutics for patients with cryptococcosis.

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Invasive mold disease of the central nervous system in children and adolescents with cancer or undergoing hematopoietic stem cell transplantation: Analysis of 29 contemporary patients

Lauten

Attarbaschi

Cario

et al. 2019

Pediatric Blood & Cancer

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Background Invasive mold disease (IMD) is a severe infectious complication in immunocompromised patients. The outcome of central nervous system (CNS) IMD is poor, but contemporary data, in particular in the pediatric setting, are lacking. Procedure For this retrospective multicenter analysis, pediatric patients < 18 years with proven or probable CNS IMD receiving chemotherapy or undergoing allogeneic HSCT were reported by the local investigator. CNS IMD had to be diagnosed between 2007 and 2016. Proven CNS IMD was defined as compatible CNS imaging or macroscopic autopsy findings in conjunction with a positive microscopic or microbiological result in the brain tissue or cerebrospinal fluid. Probable CNS IMD was defined as compatible CNS imaging findings in combination with proven or probable IMD at a site outside the CNS. Results and conclusions A total of 29 patients (median age, 14 years; 14 allogeneic HSCT recipients) were diagnosed with proven (n = 12) or probable (n = 17) CNS IMD. Aspergillus spp. was the most common fungal pathogen. All but one patient had IMD sites outside the CNS and eight patients (27.6%) were neurologically asymptomatic at diagnosis of CNS IMD. Forty‐nine percent of the patients survived CNS IMD; however, 46.7% of the survivors suffered from severe long‐term neurological sequelae. Our data suggest that (1) outcome of CNS IMD has improved in children as compared with previous series, (2) half of surviving patients suffer from severe neurological sequelae, and (3) imaging of the CNS should be performed in all children with IMD irrespective of neurological symptoms.

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Advances in the diagnosis and treatment of fungal infections of the CNS

Cited by 102 publications

References 95 publications

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

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

Screening and Synthesis of Tetrazole Derivatives that Inhibit the Growth of Cryptococcus Species

Invasive mold disease of the central nervous system in children and adolescents with cancer or undergoing hematopoietic stem cell transplantation: Analysis of 29 contemporary patients

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