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1.
EBioMedicine ; 66: 103288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33752127

RESUMO

BACKGROUND: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. METHODS: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. FINDINGS: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. INTERPRETATION: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Itraconazol/farmacologia , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/uso terapêutico , COVID-19/etiologia , COVID-19/transmissão , Chlorocebus aethiops , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacocinética , Itraconazol/uso terapêutico , Masculino , Mesocricetus , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudo de Prova de Conceito , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento , Células Vero
3.
s.l; s.n; 2021. 6 p. tab, ilus.
Não convencional em Inglês | Sec. Est. Saúde SP, CONASS, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1146794

RESUMO

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective(AU).


Assuntos
Humanos , Masculino , Feminino , Quimioterapia Combinada , Lobomicose/tratamento farmacológico , Rifampina/uso terapêutico , Clofazimina/uso terapêutico , Itraconazol/uso terapêutico , Dapsona/uso terapêutico , Hanseníase/tratamento farmacológico
5.
Artigo em Inglês | MEDLINE | ID: mdl-33206863

RESUMO

Paracoccidioidomycosis caused by Paracoccidioides lutzii is endemic in the Midwest of Brazil and its clinical spectrum is still little known due to the recent identification of this fungal species. A patient resident in Southeast Brazil, but who had lived for many years in the Midwest region, presented with skin injuries, chronic cough and bilateral adrenal involvement. Paracoccidioides spp. was isolated in culture from a skin lesion biopsy. This isolate was later identified as P. lutzii using gene sequencing. A favorable initial response to treatment with itraconazole was observed, but a few weeks later, the patient developed respiratory failure and worsening of lung lesions. Evaluation by computed tomography and echocardiography were suggestive of pulmonary arterial hypertension, and a bronchoscopic biopsy showed peribronchial remodeling. The patient completed the antifungal treatment but maintained the respiratory dysfunction. The reported case shows that P. lutzii can be isolated from patients in a geographic area far from the place of infection acquisition and that, as P. brasiliensis , it can cause adrenal injury and cardio-respiratory complications as a consequence of excessive necrosis and fibrosis.


Assuntos
Paracoccidioides/isolamento & purificação , Paracoccidioidomicose , Brasil , Humanos , Itraconazol/uso terapêutico , Paracoccidioides/classificação , Paracoccidioidomicose/complicações , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/tratamento farmacológico , Hipertensão Arterial Pulmonar
7.
BMC Infect Dis ; 20(1): 717, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993529

RESUMO

BACKGROUND: Fungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). CASE PRESENTATION: An 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable. CONCLUSION: H. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.


Assuntos
Histoplasma/isolamento & purificação , Histoplasmose/diagnóstico , Histoplasmose/etiologia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/diagnóstico , Peritonite/etiologia , Administração Intravenosa , Administração Oral , Idoso de 80 Anos ou mais , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Ásia , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Histoplasmose/tratamento farmacológico , Histoplasmose/microbiologia , Humanos , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Falência Renal Crônica/terapia , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Resultado do Tratamento
9.
An Bras Dermatol ; 95(6): 740-742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32912801

RESUMO

Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400mg/day in the first month, decreased to 200mg/day until the sixth month of treatment.


Assuntos
Paracoccidioidomicose , Idoso , Antifúngicos/uso terapêutico , Feminino , Humanos , Itraconazol/uso terapêutico , Pulmão , Masculino , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/tratamento farmacológico
10.
Artigo em Inglês | MEDLINE | ID: mdl-32876295

RESUMO

Sporotrichosis is an implantation mycosis highly prevalent in Brazil, associated with soil activities and contact with infected animals. It has numerous clinical manifestations and its disseminated cutaneous form is uncommon, found in approximately 4% of cases and usually related to immunosuppressive conditions. We report an alcoholic 56-year-old male patient with no other comorbidities, presenting with multiple cutaneous nodules and ulcers. The patient was diagnosed with disseminated cutaneous sporotrichosis based on the isolation and identification of Sporothrix spp. The patient was initially treated with amphotericin B with satisfactory results and then with itraconazole.


Assuntos
Alcoolismo/complicações , Sporothrix/isolamento & purificação , Esporotricose/diagnóstico , Anfotericina B/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Brasil , Humanos , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esporotricose/tratamento farmacológico , Resultado do Tratamento , Úlcera/etiologia
11.
Am J Trop Med Hyg ; 103(5): 1852-1854, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815507

RESUMO

Chromoblastomycosis is a cutaneous fungal infection caused by dematiaceous fungi that belong to the order Chaetothyriales and family Herpotrichiellaceae. This infection is prevalent in tropical and subtropical areas and has been designated as a neglected tropical disease according to the WHO. Chromoblastomycosis infection is difficult to treat, and there are limited therapeutic options, making urgent the characterization of new medicines or approaches to treat such infection. In the present case report, two patients with extensive chromoblastomycosis lesions were treated with the combination of itraconazole, acitretin, and imiquimod. In the fourth month of treatment, both patients showed improvement of verrucous plates, suggesting that acitretin combined with drugs already used in chromoblastomycosis therapy can decrease the time of treatment, improving patient's quality of life.


Assuntos
Acitretina/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/patologia , Imiquimode/uso terapêutico , Itraconazol/uso terapêutico , Acitretina/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Quimioterapia Combinada , Humanos , Imiquimode/administração & dosagem , Itraconazol/administração & dosagem , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Masculino , Pessoa de Meia-Idade
13.
BMC Infect Dis ; 20(1): 562, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738901

RESUMO

BACKGROUND: Morbidity and mortality in transplant patients is increased by infection caused mainly by rare opportunistic pathogens. The present study reports a case where Hongkongmyces snookiorum caused subcutaneous phaeohyphomycosis in a kidney transplant patient. CASE PRESENTATION: A 47-year old Chinese woman with chronic kidney disease 5 underwent kidney transplantation 3 years ago. Her regular medications included Tacrolimus (1 mg, two times daily), Mycophenolate Mofetil (two times 250 mg, twice daily) and Prednisone acetate tablets (5 mg daily). Eighteen months ago, her proximal right index finger was red, painful and swollen. After admission, a hard and fluctuating 1 cm × 1 cm abscess was found on the dorsal side of the right index finger. Gram and fluorescence staining of a direct smear of a syringe extraction from the abscess revealed presence of filamentous fungi. White velvet colonies (2-3 mm) were found on blood plate and Sabouraud glucose agar (SGA) after 1 week, and grey aerial hyphae were observed. After 15 days, a 26 mm gray colony was also observed on SGA. The homology between this filamentous fungus and Hongkongmyces snookiorum ILLS00125755 (Genbank Sequence ID: MH161189.1) was 99.66%. An in vitro antifungal susceptibility test showed that this filamentous fungus was sensitive to azoles such as itraconazole and voriconazole. CONCLUSIONS: We report an opportunistic fungus infection caused by Hongkongmyces snookiorum in a transplant patient. Our finding shows that prevention of subcutaneous fungal infection is necessary for kidney transplantation patients.


Assuntos
Ascomicetos/isolamento & purificação , Transplante de Rim/efeitos adversos , Feoifomicose/etiologia , Antifúngicos/uso terapêutico , Feminino , Humanos , Itraconazol/uso terapêutico , Pessoa de Meia-Idade , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Insuficiência Renal Crônica/terapia , Voriconazol/uso terapêutico
14.
J Vet Med Sci ; 82(10): 1492-1496, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32848107

RESUMO

A 3-month-old male Scottish Fold kitten with pleural fluid and low ratio of albumin to globulin (A/G ratio) was brought to our small animal hospital. Since RNA from the type I feline coronavirus (FCoV) were detected in drained pleural fluid, the cat was tentatively diagnosed with effusive feline infectious peritonitis (FIP). Following the administration of itraconazole and prednisolone, the A/G ratio increased, and the pleural fluid mostly disappeared. The fecal FCoV levels temporarily decreased. However, the cat showed neurological manifestations and was eventually euthanized due to status epilepticus after 38 days of treatment. In conclusion, itraconazole partly exerted a beneficial effect in a cat with FIP. However, further investigation of a possible role of itraconazole in FIP treatment is warranted.


Assuntos
Inibidores de 14-alfa Desmetilase/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Peritonite Infecciosa Felina/tratamento farmacológico , Itraconazol/uso terapêutico , Prednisolona/uso terapêutico , Inibidores de 14-alfa Desmetilase/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Líquidos Corporais/virologia , Gatos , Coronavirus Felino/isolamento & purificação , Peritonite Infecciosa Felina/complicações , Itraconazol/administração & dosagem , Masculino , Prednisolona/administração & dosagem , RNA Viral/química , Estado Epiléptico/patologia , Estado Epiléptico/veterinária
17.
Adv Clin Exp Med ; 29(5): 535-545, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32458595

RESUMO

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by a loss of myelin, limb disabilities and dysregulation of gene expression. Unfortunately, there still is no treatment to cure MS. OBJECTIVES: To explore a novel way to treat MS using currently available antifungal drugs. MATERIAL AND METHODS: We built an experimental autoimmune encephalomyelitis (EAE) model to mimic MS and tested the effect of an antifungal drug - itraconazole - on EAE by comparing it with a phosphate-buffered saline (PBS) control group. We assessed the animal limb deficits with Weaver's scoring and used histology staining (including luxol fast blue (LFB) and hematoxylin & eosin (H&E) methods) to determine the demyelination in the spinal tissues. We also performed western blotting to quantify the expression changes of proteins related to endoplasmic reticulum (ER) stress response and apoptosis. RESULTS: The limb disabilities were greatly diminished and the demyelination in the spinal tissues of the EAE mice was mostly reduced following itraconazole treatment. The hyperactivation of the ER stress response and apoptosis pathway in EAE was also significantly diminished by the itraconazole treatment. In addition, the AMPK pathway was downregulated in EAE, its expression level bi-directionally affected the activity of the ER stress response, and its downregulation removed the beneficial effect of itraconazole. CONCLUSIONS: Our study revealed a new method for treating MS using currently approved antifungal drugs.


Assuntos
Antifúngicos/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Itraconazol/uso terapêutico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla
18.
Cochrane Database Syst Rev ; 4: CD013594, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343003

RESUMO

BACKGROUND: Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear. OBJECTIVES: We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020. SELECTION CRITERIA: We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single-arm trials, prospective cohort studies, and single-arm cohort studies. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS-I tool to assess risk of bias in non-randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI). MAIN RESULTS: We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low-certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high-certainty evidence). We found very low-certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died. AUTHORS' CONCLUSIONS: Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Infecções por HIV/complicações , Histoplasmose/tratamento farmacológico , Anfotericina B/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/efeitos adversos , Estudos de Coortes , Ácido Desoxicólico , Esquema de Medicação , Fluconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Histoplasmose/mortalidade , Humanos , Quimioterapia de Indução , Itraconazol/uso terapêutico , Rim/efeitos dos fármacos , Lipossomos , Quimioterapia de Manutenção , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
A A Pract ; 14(6): e01181, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32224696

RESUMO

Utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is expanding, but dual VA-ECMO circuits to treat cardiogenic shock with refractory hypoxemia is unreported. We describe the case of combined cardiogenic and distributive shock due to necrotizing pulmonary blastomycosis. After initial central VA-ECMO cannulation, acute respiratory distress syndrome (ARDS) with increasing shunt resulted in significant central hypoxemia due to progressive ventilation-perfusion mismatch. An additional circuit provided complete oxygenation of the high circulating volume. After 4 months on support, he underwent successful heart-lung-kidney transplantation. Dual ECMO circuits are technically feasible and may be advantageous in specific circumstances of high pulmonary shunting resulting in excessive hypoxemia unbalanced with appropriate oxygen delivery.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hipóxia/terapia , Pneumonia Necrosante/complicações , Choque Cardiogênico/terapia , Adulto , Anfotericina B/uso terapêutico , Evolução Fatal , Humanos , Hipóxia/etiologia , Itraconazol/uso terapêutico , Masculino , Pneumonia Necrosante/tratamento farmacológico , Choque Cardiogênico/etiologia
20.
An Bras Dermatol ; 95(2): 241-243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32165024

RESUMO

Sporotrichosis is a deep mycosis of subacute or chronic evolution, caused by the dimorphic fungus of the genus Sporothrix. The treatment is carried out with antifungal orally or intravenously. Therapeutic success can be affected by several factors, such as altered gastrointestinal physiology by surgery. More and more patients are submitted to bariatric surgeries and the literature for the alterations of the absorption of medications in this context is very scarce. We intend to contribute to a better understanding with this case report of cutaneous-lymphatic sporotrichosis in a patient after bariatric surgery without response to itraconazole treatment, even at high doses.


Assuntos
Antifúngicos/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Itraconazol/uso terapêutico , Esporotricose/tratamento farmacológico , Adulto , Feminino , Absorção Gastrointestinal , Humanos , Esporotricose/patologia , Falha de Tratamento
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