Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

Schiave, Letícia Aparecida; Nascimento, Érika; Vilar, Fernando Crivelenti; Haes, Tissiana Marques de; Takayanagui, Osvaldo Massaiti; Gaitani, Cristiane Masetto de; Martínez, Roberto

doi:10.1016/j.bjid.2017.10.003

Cited by 10 publications

(7 citation statements)

References 27 publications

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“… Reichert-Lima et al (2016) C. neoformans and C. gattii isolates from both HIV-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease Nascimento et al (2017) FCZ non-susceptible C. neoformans . Use of LAmB in AIDS patient Santana et al (2017) FCZ levels in serum and cerebrospinal fluid Schiave et al (2018) Time-kill curves studies with AmB against C. neoformans / C . gattii species complex clinical isolates de Oliveira et al (2017) Heteroresistance to FCZ in clinical and environmental strains of C. neoformans and C. gattii Feliciano et al (2017) Cuba C. neoformans , FCZ susceptibility Fernández-Andreu et al (1999) New azoles and C. neoformans Cuban clinical isolates Illnait-Zaragozi et al (2008) FCZ, VCZ susceptibility of Cuban isolates Illnait-Zaragozi et al (2009) Venezuela A review of C. neoformans ECVs Ferrara et al (2017) AmB: amphotericin B; FCZ: fluconazole; ITZ: itraconazole; PCZ: posaconazole; VCZ: voriconazole.…”

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confidence: 99%

The status of cryptococcosis in Latin America

Firacative

Lizarazo

Illnait-Zaragozí

et al. 2018

Mem. Inst. Oswaldo Cruz

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Cryptococcosis is a life-threatening fungal infection caused by the encapsulated yeasts Cryptococcus neoformans and C. gattii, acquired from the environment. In Latin America, as occurring worldwide, C. neoformans causes more than 90% of the cases of cryptococcosis, affecting predominantly patients with HIV, while C. gattii generally affects otherwise healthy individuals. In this region, cryptococcal meningitis is the most common presentation, with amphotericin B and fluconazole being the antifungal drugs of choice. Avian droppings are the predominant environmental reservoir of C. neoformans, while C. gattii is associated with several arboreal species. Importantly, C. gattii has a high prevalence in Latin America and has been proposed to be the likely origin of some C. gattii populations in North America. Thus, in the recent years, significant progress has been made with the study of the basic biology and laboratory identification of cryptococcal strains, in understanding their ecology, population genetics, host-pathogen interactions, and the clinical epidemiology of this important mycosis in Latin America.

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mentioning

confidence: 99%

The status of cryptococcosis in Latin America

Firacative

Lizarazo

Illnait-Zaragozí

et al. 2018

Mem. Inst. Oswaldo Cruz

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“…Moreover, tumor necrosis factor alpha (TNF-␣) and lipopolysaccharide (LPS) increased the permeability of the BBB to amphotericin B significantly in comparison to that for the controls. The in vitro BBB model system also predicted the CNS permeation properties of fluconazole (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Amphotericin B Penetrates into the Central Nervous System through Focal Disruption of the Blood-Brain Barrier in Experimental Hematogenous Candida Meningoencephalitis

Petraitis

Petraitienė

Valdez

et al. 2019

Antimicrob Agents Chemother

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Hematogenous Candida meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeation and low cerebrospinal fluid (CSF) concentrations but is effective in the treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions. An in vitro blood-brain barrier (BBB) model was serially infected with Candida albicans. Liposomal AmB (LAMB) or deoxycholate AmB (DAMB) at 5 μg/ml was then provided, and the vascular and CNS compartments were sampled 4 h later. For in vivo correlation, rabbits with experimental HCME received a single dose of DAMB at 1 mg/kg of body weight or LAMB at 5 mg/kg and were euthanized after 1, 3, 6, and 24 h. Evans blue dye solution (2%, 2 ml/kg) administered intravenously (i.v.) at 1 h prior to euthanasia stained infected regions of tissue but not histologically normal areas. AmB concentrations in stained and unstained tissue regions were measured using ultraperformance liquid chromatography. For selected rabbits, magnetic resonance imaging (MRI) scans performed on days 1 to 7 postinoculation were acquired before and after i.v. bolus administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) at 15-min intervals through 2 h postinjection. The greatest degree of penetration of DAMB and LAMB through the in vitro BBB occurred after 24 h of exposure (P = 0.0022). In vivo the concentrations of LAMB and DAMB in brain abscesses were 4.35 ± 0.59 and 3.14 ± 0.89 times higher, respectively, than those in normal tissue (P ≤ 0.019). MRI scans demonstrated that Gd-DTPA accumulated in infected areas with a disrupted BBB. Localized BBB disruption in HCME allows high concentrations of AmB within infected tissues, despite the presence of low cerebrospinal fluid concentrations.

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“…FLC exhibits linear pharmacokinetics and excellent distribution into various tissues and body fluids, reaching a broad range of physiological concentrations. Serum concentrations are dose-dependent, with typical doses of 200–800 mg/day FLC corresponding to serum concentrations of ∼7.5–60.5 μg/ml FLC ( Schiave et al 2018 ). FLC levels reach peak serum concentration 1–6 h after administration and remain in the system for days (elimination half-life is ∼30 h in individuals with functioning kidneys [ Cousin 2003 ]).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, FLC concentrations vary between different tissues in the body (1 μg/ml to over 22 μg/ml), with the highest concentration of FLC being detected in the spleen ( Fischman et al 1993 ). Lower doses of FLC are used as prophylaxis for patients undergoing solid tissue transplantation ( Felton et al 2014 ; Pappas et al 2016 ; Schiave et al 2018 ) and recurrent vulvovaginal candidiasis ( Denning et al 2018 ), however higher daily doses of FLC may result in longer survival of patients with candidiasis ( Schiave et al 2018 ). Why different drug concentration influence treatment success remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans

Todd

Soisangwan

Peters

et al. 2023

Molecular Biology and Evolution

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Invasive fungal infections are a leading global cause of human mortality. Only three major classes of antifungal drugs are widely used, and resistance to all three classes can arise rapidly. The most widely prescribed antifungal drug, fluconazole, disseminates rapidly and reaches a wide range of concentrations throughout the body. The impact of drug concentration on the spectrum and effect of mutations acquired during adaptation is not known for any fungal pathogen, and how the specific level of a given stress influences the distribution of beneficial mutations has been poorly explored in general. We evolved 144 lineages from three genetically distinct clinical isolates of Candida albicans to four concentrations of fluconazole (0, 1, 8, and 64 μg/ml) and performed comprehensive phenotypic and genomic comparisons of ancestral and evolved populations. Adaptation to different fluconazole concentrations resulted in distinct adaptive trajectories. In general, lineages evolved to drug concentrations close to their MIC50 (the level of drug that reduces growth by 50% in the ancestor) tended to rapidly evolve an increased MIC50 and acquired distinct segmental aneuploidies and copy number variations. By contrast, lineages evolved to drug concentrations above their ancestral MIC50 tended to acquire a different suite of mutational changes and increased in drug tolerance (the ability of a subpopulation of cells to grow slowly above their MIC50). This is the first evidence that different concentrations of drug can select for different genotypic and phenotypic outcomes in vitro and may explain observed in vivo drug response variation.

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Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

Cited by 10 publications

References 27 publications

The status of cryptococcosis in Latin America

The status of cryptococcosis in Latin America

Amphotericin B Penetrates into the Central Nervous System through Focal Disruption of the Blood-Brain Barrier in Experimental Hematogenous Candida Meningoencephalitis

Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans

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