Fungal Infections of the Central Nervous System

Carod-Artal, Francisco Javier

doi:10.1007/978-3-319-70296-4_7

Cited by 4 publications

(3 citation statements)

References 126 publications

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“…However, other noncryptococcal, but amphotericin-responsive fungal infections occasionally cause CM (particularly histoplasmosis and, rarely, candida, paracoccidioidomycosis, and sporotrichosis). [68][69][70] Hence, after an empirical nonresponsive use of medications to M. tuberculosis and other bacterial infections, a trial with amphotericin could be considered. In patients with CM and severe neurological manifestations (i.e., in intensive care unit), after excluding cryptococcal meningitis, immediate empirical treatment with antibiotics and tuberculostatics should be prescribed.…”

Section: Empirical Treatment In Chronic Meningitis Of Unknown Etiologymentioning

confidence: 99%

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review

et al. 2022

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Background Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce. Objective To critically review the literature on CM and propose a rational approach in the Brazilian scenario. Methods Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil. Results In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data. Conclusion We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.

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Section: Empirical Treatment In Chronic Meningitis Of Unknown Etiologymentioning

confidence: 99%

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review

et al. 2022

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“…Cryptococcal meningitis is one of the most common fungal infections that affect the central nervous system (CNS), accounting for a large number of deaths annually [ 1 , 2 , 3 ]. The treatment of this infection comprises the use of amphotericin B (AmB), flucytosine (5-FH) and fluconazole (FLU) [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Modeling and Simulation as a Tool to Assess Voriconazole Exposure in the Central Nervous System

et al. 2023

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Voriconazole is a triazole antifungal used empirically for the treatment of complicated meningitis associated with Cryptococcus neoformans. Biopsy studies show that the drug exhibits adequate brain penetration although levels of cerebral spinal fluid (CSF) are highly variable. Considering that CSF is one of the main surrogates for CNS exposure, the present work proposed the building of a population pharmacokinetic modeling (popPK) model able to describing the exposure achieved by voriconazole in the plasma, interstitial cerebral fluid and CSF of healthy and infected rats. The developed popPK model was described by four compartments, including total plasma, free brain and total CSF concentrations. The following PK parameters were determined: Km = 4.76 mg/L, Vmax = 1.06 mg/h, Q1 = 2.69 L, Qin = 0.81 h−1 and Qout = 0.63 h−1. Infection was a covariate in the Michaelis–Menten constant (Km) and intercompartmental clearance from the brain tissue compartment to central compartment (Qout). Simulations performed with the popPK model to determine the probability of reaching the therapeutic target of fAUC > MIC showed that VRC has sufficient tissue exposure in the interstitial fluid and in the CSF for the treatment of fungal infections in these tissues at prevalent minimum inhibitory concentrations.

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“…Rhizopus spp. are responsible for more than 50% of all mucormycosis cases in the respiratory tract or central nervous system worldwide and are often found in cutaneous wounds [16,17].…”

Section: Introductionmentioning

confidence: 99%

Hyphae of Rhizopus arrhizus and Lichtheimia corymbifera Are More Virulent and Resistant to Antifungal Agents Than Sporangiospores In Vitro and in Galleria mellonella

Samdavid Thanapaul,

Roberds,

Rios

et al. 2023

JoF

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Mucorales species cause debilitating, life-threatening sinopulmonary diseases in immunocompromised patients and penetrating wounds in trauma victims. Common antifungal agents against mucormycosis have significant toxicity and are often ineffective. To evaluate treatments against mucormycosis, sporangiospores are typically used for in vitro assays and in pre-clinical animal models of pulmonary infections. However, in clinical cases of wound mucormycosis caused by traumatic inoculation, hyphal elements found in soil are likely the form of the inoculated organism. In this study, Galleria mellonella larvae were infected with either sporangiospores or hyphae of Rhizopus arrhizus and Lichtheimia corymbifera. Hyphal infections resulted in greater and more rapid larval lethality than sporangiospores, with an approximate 10–16-fold decrease in LD50 of hyphae for R. arrhizus (p = 0.03) and L. corymbifera (p = 0.001). Liposomal amphotericin B, 10 mg/kg, was ineffective against hyphal infection, while the same dosage was effective against infections produced by sporangiospores. Furthermore, in vitro, antifungal susceptibility studies show that minimum inhibitory concentrations of several antifungal agents against hyphae were higher when compared to those of sporangiospores. These findings support using hyphal elements of Mucorales species for virulence testing and antifungal drug screening in vitro and in G. mellonella for studies of wound mucormycosis.

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Fungal Infections of the Central Nervous System

Cited by 4 publications

References 126 publications

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review

Modeling and Simulation as a Tool to Assess Voriconazole Exposure in the Central Nervous System

Hyphae of Rhizopus arrhizus and Lichtheimia corymbifera Are More Virulent and Resistant to Antifungal Agents Than Sporangiospores In Vitro and in Galleria mellonella

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