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1.
Front Cell Infect Microbiol ; 11: 711768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796121

RESUMO

Objective: Dirkmeia churashimaensis, belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents. Methods: An 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis, as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections. Results: Local barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn's disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections. Conclusions: The present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections.


Assuntos
Micoses , Ustilaginales , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Basidiomycota , Equinocandinas , Fluconazol , Humanos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Voriconazol
2.
Drugs R D ; 21(4): 419-429, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655050

RESUMO

OBJECTIVE: The aim of this study was to identify factors affecting blood concentrations of voriconazole following letermovir coadministration using population pharmacokinetic (PPK) analysis in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The following data were retrospectively collected: voriconazole trough levels, patient characteristics, concomitant drugs, and laboratory information. PPK analysis was performed with NONMEM® version 7.4.3, using the first-order conditional estimation method with interaction. We collected data on plasma voriconazole steady-state trough concentrations at 216 timepoints for 47 patients. A nonlinear pharmacokinetic model with the Michaelis-Menten equation was applied to describe the relationship between steady-state trough concentration and daily maintenance dose of voriconazole. After stepwise covariate modeling, the final model was evaluated using a goodness-of-fit plot, case deletion diagnostics, and bootstrap methods. RESULTS: The maximum elimination rate (Vmax) of voriconazole in patients coadministered letermovir and methylprednisolone was 1.72 and 1.30 times larger than that in patients not coadministered these drugs, respectively, resulting in decreased voriconazole trough concentrations. The developed PPK model adequately described the voriconazole trough concentration profiles in allo-HSCT recipients. Simulations clearly showed that increased daily doses of voriconazole were required to achieve an optimal trough voriconazole concentration (1-5 mg/L) when patients received voriconazole with letermovir and/or methylprednisolone. CONCLUSIONS: The development of individualized dose adjustment is critical to achieve optimal voriconazole concentration, especially among allo-HSCT recipients receiving concomitant letermovir and/or methylprednisolone.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Metilprednisolona , Acetatos , Antifúngicos , Humanos , Quinazolinas , Estudos Retrospectivos , Voriconazol
4.
Rev Chilena Infectol ; 38(4): 568-573, 2021 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-34652405

RESUMO

We report a case of invasive fungal infection with necrotizing conjunctivitis, scleritis and unilateral panuveitis caused by Scedosporium apiospermum in a 78-year-old woman that developed neutropenia by drugs indicated for rheumatoid arthritis. The etiological diagnosis was confirmed by mycological culture of an ocular secretion with the support of MALDI-TOF-TOF analysis and histopathological findings. The treatment involved surgical debridements together with topical solution and systemic therapy with voriconazole and steroids with a favorable evolution after 2 months of treatment. A relapse required a second therapeutic course for an additional 12 months with improvement and eradication of the agent. Fungal conjunctivitis due to S. apiospermum is a rare event associated with immunosuppressed patients. Its treatment involves surgical debridements and prolonged antifungal therapy.


Assuntos
Infecções Oculares Fúngicas , Infecções Fúngicas Invasivas , Scedosporium , Idoso , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Feminino , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/tratamento farmacológico , Voriconazol/uso terapêutico
5.
J Med Microbiol ; 70(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491156

RESUMO

Introduction. The increase of invasive fungal infections (IFIs) and associated treatment failure in populations at risk is driving us to look for new treatments.Hypothesis. The CIN-102 compound, derived from cinnamon essential oil, could be a new antifungal class with an activity, in particular, on strains resistant to current antifungals but also on biofilms, a factor of virulence and resistance of fungi.Aim. The aim of this study is to show the activity of CIN-102 on various strains resistant to current antifungals, on the biofilm and to determine the possibility of resistance induced with this compound.Methodology. We studied the MIC of CIN-102 and of current antifungals (voriconazole and amphotericin B) using CLSI techniques against eight different strains of three genera of filamentous fungi involved in IFIs and having resistance phenotypes to current antifungals. We also determined their effects on biofilm formation, and the induced resistance by voriconazole (VRC) and CIN-102.Results. MIC values determined for CIN-102 were between 62.5 and 250 µg ml-1. We demonstrated the antifungal effect of CIN-102 on biofilm, and more particularly on its formation, with 100 % inhibition achieved for most of the strains. CIN-102 at a sub-inhibitory concentration in the medium did not induce resistance in our strains, even after 30 generations.Conclusions. In this study we show that CIN-102 is effective against resistant filamentous fungi and against biofilm formation. In addition, our strains did not acquire a resistance phenotype against CIN-102 over time, unlike with VRC. CIN-102 is therefore an interesting candidate for the treatment of IFIs, including in cases of therapeutic failure linked to resistance, although further studies on its efficacy, safety and mechanism of action are needed.


Assuntos
Antifúngicos/farmacologia , Benzoatos/farmacologia , Biofilmes/efeitos dos fármacos , Cinamatos/farmacologia , Fungos/efeitos dos fármacos , Micoses , Terpenos/farmacologia , Anfotericina B/farmacologia , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Micoses/microbiologia , Voriconazol/farmacologia
6.
Anal Methods ; 13(39): 4585-4593, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34532726

RESUMO

Background: A liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method: For the quantification of voriconazole in human cerebrospinal fluid (CSF) was developed and validated, to guide the clinical use of voriconazole in the treatment of central nervous system infections. CSF samples were treated by protein precipitation with methanol containing fluconazole as the internal standard (IS). The supernatant was analyzed by LC-MS/MS using an Agilent EclipsePlus C18 column eluted with a methanol and water mobile phase at a flow rate of 0.4 mL min-1. Quantification was performed by multiple-reaction monitoring using the precursor and product ion pair 350/280.9 for voriconazole and 307/219.9 for fluconazole. Results: The calibration curve was linear over the range of 0.1-10.0 µg mL-1 (R2 = 0.9991). The inter-day and intra-day precisions were <4.20% and <9.97%, respectively. The recoveries for the three concentrations (0.2, 1.0, and 8.0 µg mL-1) were 99.96%, 107.00%, and 99.85%, and the matrix effects were 99.35%, 103.41%, and 99.64%, respectively. The stability under various conditions was also acceptable. The study also demonstrated that the CSF matrix could be replaced by plasma and artificial CSF. Conclusion: A simple and accurate method for the determination of voriconazole concentrations in human CSF was developed and validated, which can be used for drug monitoring in the treatment of central nervous system infections.


Assuntos
Monitoramento de Medicamentos , Espectrometria de Massas em Tandem , Cromatografia Líquida , Humanos , Reprodutibilidade dos Testes , Voriconazol
7.
Zhonghua Er Ke Za Zhi ; 59(10): 871-875, 2021 Oct 02.
Artigo em Chinês | MEDLINE | ID: mdl-34587685

RESUMO

Objective: To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children. Methods: The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children's Hospital were retrospectively analyzed. Results: The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence. Conclusions: CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergilose Pulmonar , Adolescente , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergillus fumigatus , Criança , Feminino , Humanos , Masculino , Aspergilose Pulmonar/complicações , Estudos Retrospectivos , Voriconazol
8.
An Acad Bras Cienc ; 93(suppl 3): e20200997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550200

RESUMO

Aspergillus genus causes many diseases, and the species Aspergillus flavus is highly virulent. Treatment of aspergillosis involves azole derivatives such as voriconazole and polyenes such as amphotericin B. Due to an increase in fungal resistance, treatments are now less effective; the search for new compounds with promising antifungal activity has gained importance. The aims of this study were to evaluate the effects of the synthetic amide 2-chloro-N-phenylacetamide (A1Cl) against strains of Aspergillus flavus and to elucidate its mechanism of action. Thus, the minimum inhibitory concentration, minimum fungicidal concentration, conidial germination, associations with antifungal agents, cell wall activities, membrane activities and molecular docking were evaluated. A1Cl presented antifungal activity against Aspergillus flavus strains with a minimum inhibitory concentration of between 16 and 256 µg/mL and a minimum fungicidal concentration between 32 and 512 µg/mL. The minimum inhibitory concentration of A1Cl also inhibited conidial germination, but when associated with amphotericin B and voriconazole, it promoted antagonistic effects. Binding to ergosterol on the fungal plasma membrane is the likely mechanism of action, along with possible inhibition of DNA synthesis through the inhibition of thymidylate synthase. It is concluded that the amide 2-chloro-N-phenylacetamide has promising antifungal potential.


Assuntos
Antifúngicos , Aspergillus flavus , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Triazóis , Voriconazol/farmacologia
10.
Indian J Ophthalmol ; 69(10): 2670-2674, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34571612

RESUMO

Purpose: To evaluate the outcomes of water-soluble intrastromal natamycin (IS-NTM) as an adjunct therapy for recalcitrant fungal keratitis. Methods: This was a prospective interventional pilot study in the setting of a tertiary eye-care center. Twenty eyes of 20 consecutive patients with microbiologically proven recalcitrant fungal keratitis (ulcer size >2 mm, depth >50%, and not responding to topical NTM for 2 weeks) were recruited. The selected patients were injected with a novel composition of IS-NTM (10 ug/0.1 mL, soluble natamycin) prepared aseptically in the ocular pharmacology department. All the patients continued using topical NTM suspension 5% 4-hourly until the ulcer healed. Repeat injections were undertaken after 72 h depending on the clinical response and all the patients were followed till 6 months. Results: The mean age of the patients was 40.42 ± 10.09 years. The mean duration of the presentation was 20.8 ± 5.1 days. The most commonly isolated organisms were Aspergillus sp. (12/20, 60%) and Fusarium sp. (8/20, 40%). No patient had iatrogenic perforation or precipitate formation after IS-NTM injection. The overall cure rate with IS-NTM was 95% (19/20 patients). The number of patients who healed with the 1st, 2nd, and 3rd injection was 13, 5, and 1, respectively. One (5%) had no response to treatment and was subjected to penetrating keratoplasty. The average time taken for the resolution of the epithelial defect, stromal infiltrates, and hypopyon was 34 ± 5.2 days, 35.3 ± 6.4 days, and 15 ± 2.5 days. Healing with deep vascularization and cataract was noted in 6/19 eyes (31%) and 13/19 eyes (68.42%), respectively. Conclusion: Intrastromal injection of a novel formulation of NTM holds a promising role as adjunctive therapy to topical NTM in the management of recalcitrant filamentous fungal keratitis. The preliminary results are encouraging and further studies are required to validate the results.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Adulto , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Pessoa de Meia-Idade , Natamicina , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Voriconazol
11.
Am J Case Rep ; 22: e932544, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373441

RESUMO

BACKGROUND Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. It has a remarkably high resistance profile with few effective antifungal agents, mostly limited to voriconazole and liposomal amphotericin B. Drug-induced liver injury (DILI) by 1 of these 2 antifungal agents further complicates the management of these infections. CASE REPORT A 38-year-old woman with short bowel syndrome presented to the hospital with concerns of abdominal pain and loose stools. An abdominal CT was negative for inflammatory or ischemic bowel disease, and there was no evidence of liver disease. She tested positive for SARS-CoV-2 and required transfer to the ICU due to hypotension requiring fluid resuscitation and vasopressors. On day 43 of her admission, the patient developed a low-grade fever, for which she underwent central-line and peripheral-blood cultures that were positive for Fusarium dimerum. The central line was removed and i.v. voriconazole started. After 3 days of treatment, the patient's liver enzymes rose abruptly. Voriconazole was discontinued and replaced with liposomal amphotericin B, and the liver enzymes improved significantly. The patient completed 14 days of therapy and was discharged from the hospital. CONCLUSIONS This is a case of F. dimerum infection followed by DILI from voriconazole treatment. Her infection was resolved after switching to liposomal amphotericin B, with improvement in liver enzymes on day 1 after discontinuing voriconazole. This observation demonstrates that altering antifungal classes may be an appropriate strategy when confronted with DILI.


Assuntos
COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Fusarium , Sepse , Adulto , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Humanos , SARS-CoV-2 , Sepse/tratamento farmacológico , Voriconazol/efeitos adversos
13.
Lancet ; 398(10300): 578, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391494
14.
Xenobiotica ; 51(10): 1199-1206, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34402388

RESUMO

Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study. Blood samples were collected before and 2 h after administration for subsequent testing and for the extraction of DNA samples. Voriconazole and voriconazole N-oxide in the plasma were detected by LC-MS/MS. The effect of voriconazole on CYP3A activity was evaluated by the ratio of the endogenous biomarkers 6ß-hydroxycortisol and cortisol.During the study period, the overall incidence of adverse reactions was 33.6% (with no deaths). The metabolite type of CYP2C19 and combined use of CYP2C19 enzyme inhibitors both had a significant impact on voriconazole exposure. Voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity. The exposure of CYP3A substrate in combination with metabolic enzyme inhibitors voriconazole could increase. Therefore, the combination uses with voriconazole need to be considered carefully and assessed adequately.


Assuntos
Citocromo P-450 CYP3A , Neoplasias Hematológicas , Antifúngicos , Cromatografia Líquida , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Genótipo , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Humanos , Espectrometria de Massas em Tandem , Voriconazol
16.
Antimicrob Agents Chemother ; 65(11): e0063821, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34370583

RESUMO

Scedosporium and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. Here, we assessed the ability of Scedosporium apiospermum and Fusarium solani species complex (FSSC) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB), and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] reduction assay. Planktonic cell and biofilm MIC50s were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5 to 32 mg/liter) and VRC (0.125 to 64 mg/liter) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MIC50s of D-AMB and L-AMB against S. apiospermum isolates were 1 and 2 mg/liter and against FSSC isolates were 0.5 and 1 mg/liter, respectively. Biofilm MIC50s of VRC against S. apiospermum and FSSC were 32 mg/liter and >256 mg/liter, respectively. Synergistic effects were observed at 2 to 4 mg/liter of L-AMB combined with 4 to 16 mg/liter of VRC against S. apiospermum biofilms (mean ΔE ± standard error, 17% ± 3.7%). Antagonistic interactions were found at 0.5 to 4 mg/liter of L-AMB combined with 0.125 to 16 mg/liter of VRC against FSSC isolates, at -28% ± 2%. D-AMB and L-AMB were more efficacious against S. apiospermum and FSSC biofilms than VRC.


Assuntos
Fusarium , Scedosporium , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Biofilmes , Humanos , Testes de Sensibilidade Microbiana , Voriconazol/farmacologia
17.
Mycopathologia ; 186(6): 893-895, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34455552

RESUMO

PURPOSE: To report a case of keratomycosis caused by a very rare pathogen, Myrothecium verrucaria. METHODS: This is a case report. A 53-year-old man complaint of left eye redness, irritation, intermittent pain after ashes entered his left eye. The patient was examined by slit lamp, anterior segment OCT and in vivo confocal microscopy. The HRT III-RCM image showed massive interlocking white thin lines in the cornea stroma. Corneal scrapings were collected for pathogen culture and PCR test. M. verrucaria was isolated and identified. RESULTS: Hourly topical natamycin (5%) and voriconazole (10 mg/ml) was given as well as intravenous fluconazole (200 mg per day). Treatment was continued with oral itraconazole, 200 mg/day, topical natamycin (5%), 4 times/day, and pranoprofen, 4 times/day. The therapy was tapered off over one and half a month. The cornea lesion healed with scar formation two months later. CONCLUSIONS: This is the first case report of M. verrucaria keratomycosis in China. We are the first to show the characteristic of M. verrucaria on cornea with In vivo confocal microscopy. A combination treatment of tropical natamycin, voriconazole and systemic fluconazole was effective in the treatment of M. verrucaria.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Hypocreales , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Natamicina , Voriconazol
19.
Antimicrob Agents Chemother ; 65(9): e0054921, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228541

RESUMO

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 µg/ml, respectively. Significant in vivo efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group (P values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant in vivo activity.


Assuntos
Candidíase , Fluconazol , Anidulafungina , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Nitrilas , Piridinas , Triazóis , Voriconazol/farmacologia , Voriconazol/uso terapêutico
20.
J Infect Chemother ; 27(10): 1520-1524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34215497

RESUMO

BACKGROUND: Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. CASE PRESENTATION: A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600-800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. CONCLUSIONS: CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.


Assuntos
Exophiala , Meningoencefalite , Adolescente , Antifúngicos/uso terapêutico , Humanos , Meningoencefalite/tratamento farmacológico , Voriconazol/uso terapêutico
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