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1.
Eye Contact Lens ; 46(6): e66-e68, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33044373

RESUMO

We report a rare case of dematiaceous fungus colonization in the therapeutic bandage contact lens (BCL), in an eye with peripheral ulcerative keratitis. Bandage contact lens removal and appropriate treatment resulted in improvement of the visual acuity and prevented the spread of fungus to the underlying ocular structures. Microbiological evaluation of the BCL showed dematiaceous fungal filaments, and the fungus was identified as Bipolaris species. In patients with pigmented plaque-like lesions, with BCL in situ, dematiaceous fungus on the undersurface of the BCL should be kept in mind. Patient education regarding the importance of frequent BCL replacement, proper ocular hygiene, and timely follow-up should be emphasized.


Assuntos
Ascomicetos/isolamento & purificação , Betacoronavirus , Lentes de Contato/microbiologia , Úlcera da Córnea/microbiologia , Infecções por Coronavirus/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Micoses/microbiologia , Pneumonia Viral/epidemiologia , Idoso , Antifúngicos/uso terapêutico , Bandagens , Carboximetilcelulose Sódica/uso terapêutico , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Perda de Seguimento , Masculino , Micoses/diagnóstico , Micoses/tratamento farmacológico , Natamicina/uso terapêutico , Pandemias , Tomografia de Coerência Óptica , Acuidade Visual
2.
BMC Infect Dis ; 20(1): 800, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115429

RESUMO

BACKGROUND: Talaromyces marneffei infection is an important opportunistic infection associated with acquired immune deficiency syndrome (AIDS). However, it is unusual in patients with non-AIDS and other non-immunosuppressed conditions. We report a case of delayed diagnosis of disseminated T. marneffei infection in non-AIDS, non-immunosuppressive and non-endemic conditions. CASE PRESENTATION: We describe a previously healthy 24-year-old man who complained of a 3-month history of intermittent diarrhea and a recent week of uncontrollable high fever. The HIV antibody test was negative. Enhanced abdominal computed tomography (CT) and integrated 18F-2-deoxy-2-fluoro-D-glucose position emission tomography/computed tomography (FDG PET/CT) both suspected malignant lymphoma. However, a large number of yeast-like cells were found in macrophages in cervical lymph node samples by hematoxylin and eosin stain and silver hexamine stain. Subsequent blood culture suggested T. marneffei infection. Metagenomic Next Generation Sequencing (mNGS) results suggested T. marneffei as the dominant pathogen. Unfortunately, the patient continued to develop acute liver failure and died due to adverse events associated with amphotericin B. CONCLUSIONS: Early diagnosis in HIV-negative patients who are otherwise not immunosuppressed and endemic poses a serious challenge. T. marneffei infection is an FDG-avid nonmalignant condition that may lead to false-positive FDG PET/CT scans. Nevertheless, integrated FDG PET/CT is necessary in patients with fever of unknown origin in the early period to perform earlier biopsy for histopathology and culture in highly avid sites and to avoid delays in diagnosis and treatment.


Assuntos
Linfoma/diagnóstico por imagem , Micoses/diagnóstico , Talaromyces/genética , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , China , Diagnóstico Tardio , Diagnóstico Diferencial , Evolução Fatal , Febre , HIV/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/mortalidade , Masculino , Micoses/tratamento farmacológico , Micoses/microbiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Talaromyces/isolamento & purificação , Tomografia Computadorizada por Raios X , Adulto Jovem
3.
Top Antivir Med ; 28(2): 455-458, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32886465

RESUMO

Due to COVID-19, this year marked the first virtual Conference on Retroviruses and Opportunistic Infections (CROI) in the conference's 27-year history. There were important studies presented that provided new insights into the prevention, diagnosis, and treatment of tuberculosis (TB) and other HIV coinfections. Highlights related to TB and HIV coinfections from this year's meeting are reviewed below.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Infecções Oportunistas/epidemiologia , Saúde Pública , Tuberculose/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Controle de Doenças Transmissíveis/organização & administração , Congressos como Assunto , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Masculino , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/epidemiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Gravidez , Prevalência , Prevenção Primária/métodos , Medição de Risco , Análise de Sobrevida , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Interface Usuário-Computador , Adulto Jovem
4.
Maturitas ; 140: 49-54, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972635

RESUMO

OBJECTIVE: To compare the effects of a 12-week course of 5%Pueraria mirifica gel and placebo gel on the prevalence of bacterial vaginosis, vaginal fungi, vaginal pH, vaginal health index (VHI), and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20160517002), 60 postmenopausal women were randomly assigned to a 12-week course of eitherP. mirifica gel or identical placebo gel. MAIN OUTCOME MEASURE: Vaginal Nugent score, fungal culture, pH, VHI, and genitourinary symptoms were evaluated at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the proportion of participants with an abnormal Nugent score in the P. mirifica and the placebo groups were 6.7 % (2/30) and 23.3 % (7/30), respectively (p =  0.006). The mean changes in Nugent scores and VHI were significantly higher in the P. mirifica group (p <  0.05). There were no significant decreases in the prevalence of symptoms between the two groups after treatment (p > 0.05). CONCLUSION: A 12-week course of treatment with 5 % P. mirifica vaginal gel in postmenopausal women with GSM has been proved to be effective in reducing indicators of bacterial vaginosis compared with placebo gel. Nevertheless, the effect on alleviating genital symptoms was not demonstrated.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Doenças Urogenitais Femininas/tratamento farmacológico , Micoses/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Pueraria , Método Duplo-Cego , Feminino , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Fitoterapia , Pós-Menopausa , Síndrome , Vagina/química , Vagina/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/uso terapêutico
6.
BMC Infect Dis ; 20(1): 599, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795259

RESUMO

BACKGROUND: Fungal bloodstream infections (FBI) among intensive care unit (ICU) patients are increasing. Our objective was to characterize the fungal pathogens that cause bloodstream infections and determine the epidemiology and risk factors for patient mortality among ICU patients in Meizhou, China. METHODS: Eighty-one ICU patients with FBI during their stays were included in the study conducted from January 2008 to December 2017. Blood cultures were performed and the antimicrobial susceptibility profiles of the resulting isolates were determined. Logistic multiple regression and ROC curve analysis were used to assess the risk factors for mortality among the cases. RESULTS: The prevalence of FBI in ICU patients was 0.38% (81/21,098) with a mortality rate of 36% (29/81). Ninety-eight strains of bloodstream-infecting fungi, mainly Candida spp., were identified from these patients. Candida albicans was most common (43%). Two strains of C. parapsilosis were no-sensitive to caspofungin, C. glabrata were less than 80% sensitive to azole drugs. Logistic multiple regression showed that age, serum albumin, APACHE II score, three or more underlying diseases, and length of stay in ICU were independent risk factors for mortality in FBI. ROC curve analysis showed that APACHE II scores > 19 and serum albumin ≤25 g/L were the best predictors of mortality. CONCLUSION: Candida spp. predominated with high mortality rates among cases of FBI in ICU. Thus, clinical staff should enhance overall patient monitoring and concurrently monitor fungal susceptibility to reduce mortality rates.


Assuntos
Micoses/patologia , APACHE , Idoso , Antifúngicos/uso terapêutico , Área Sob a Curva , Azóis/uso terapêutico , Candida albicans/isolamento & purificação , Candida parapsilosis/isolamento & purificação , China/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/mortalidade , Prevalência , Curva ROC , Fatores de Risco
7.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32780290

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Linfopenia/epidemiologia , Micoses/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Viroses/epidemiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/virologia , Citocinas/biossíntese , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Linfócitos/microbiologia , Linfócitos/virologia , Linfopenia/tratamento farmacológico , Linfopenia/microbiologia , Linfopenia/virologia , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia , Viroses/tratamento farmacológico , Viroses/microbiologia , Viroses/virologia
9.
Rev Chilena Infectol ; 37(1): 77-81, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730404

RESUMO

The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.


Assuntos
Antifúngicos , Ascomicetos , Leucemia Mieloide Aguda , Micoses , Sinusite , Antifúngicos/uso terapêutico , Ascomicetos/isolamento & purificação , Criança , Humanos , Leucemia Mieloide Aguda/complicações , Micoses/complicações , Micoses/tratamento farmacológico , Neutropenia/etiologia , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Resultado do Tratamento
10.
PLoS One ; 15(6): e0235193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584882

RESUMO

Antimicrobial resistance is becoming a growing health problem, which has become a challenge for the physicians to control infection and also an economic burden on the healthcare. This increase in resistance to the present antimicrobial agents led the researchers to find some alternative and more efficient drugs which can fight with the resistant microorganisms more effectively. Hence, in silico approach is used to design some novel drugs against various targets of microorganisms. For effective virtual screening of the drugs, there is a need to know about the chemical structure and properties of the antimicrobial agents. Therefore, we have prepared a comprehensive database as a platform for the researcher to search for possible lead molecules. Antimicrobial chemotherapeutics database (ACD) is comprised of ~4100 synthetic antimicrobial compounds as well as ~1030 active antimicrobial peptides. The Antimicrobial peptides are mainly from biological sources but some of them are synthetic in nature. Only those compounds, which are found to be active against either bacteria (both Gram-positive and negative) or fungus, are selected for this database.The ACD database is freely available at URL: http://amdr.amu.ac.in/acd, and it is compatible with desktops, smartphones, and tablets.


Assuntos
Anti-Infecciosos , Simulação por Computador , Bases de Dados de Produtos Farmacêuticos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Micoses/tratamento farmacológico , Animais , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Fungos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos
11.
BMC Infect Dis ; 20(1): 394, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493232

RESUMO

BACKGROUND: Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. CASE PRESENTATION: We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents' revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). CONCLUSIONS: In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.


Assuntos
Hepatopatias/diagnóstico , Micoses/diagnóstico , Fator de Transcrição STAT3/genética , Talaromyces/isolamento & purificação , Antifúngicos/uso terapêutico , Pré-Escolar , Colonoscopia , Diagnóstico Diferencial , Humanos , Mucosa Intestinal/microbiologia , Perfuração Intestinal , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Masculino , Mutação de Sentido Incorreto , Micoses/tratamento farmacológico , Micoses/microbiologia , Tomografia Computadorizada por Raios X
12.
Int J STD AIDS ; 31(7): 694-698, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32538333

RESUMO

Human immunodeficiency virus (HIV) ribonucleic acid (RNA) levels generally remain undetectable in the cerebrospinal fluid of people living with HIV with peripheral viral suppression. Secondary HIV central nervous system (CNS) escape refers to the rare independent replication of HIV RNA in the central nervous system despite peripheral viral suppression that occurs in the setting of a concomitant non-HIV infection. We describe here a young man with perinatal HIV infection considered a viral controller who developed secondary HIV CNS escape in the setting of a presumed fungal CNS infection.


Assuntos
Antirretrovirais/uso terapêutico , Sistema Nervoso Central/virologia , Líquido Cefalorraquidiano/virologia , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , Cefaleia/etiologia , Fotofobia/etiologia , Carga Viral/efeitos dos fármacos , Replicação Viral/genética , Adulto , Antifúngicos/uso terapêutico , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/fisiopatologia , Infecções por HIV/virologia , Humanos , Masculino , Micoses/tratamento farmacológico , RNA Viral/líquido cefalorraquidiano , RNA Viral/efeitos dos fármacos , RNA Viral/genética , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(15): e19735, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282732

RESUMO

INTRODUCTION: The increase in the number of patients with prosthetic joints will entail a rise in the absolute number of infections associated with these procedures. Although less frequent, infections by Candida species are also expected to increase, and the clinical and surgical management of these cases is based on case reports and opinion of specialists. The objective of the present study was to review the available literature and describe the cases of prosthetic joint infection caused by Candida species in patients of the Institute of Orthopedics and Trauma of the University of São Paulo Faculty of Medicine Clinics Hospital (IOT-HCFMUSP) between 2007 and 2014. PATIENT CONCERNS: Eleven patients were diagnosed with prosthetic joint infection due to Candida with mean age of 65 years. The most frequent comorbidities were heart disease and diabetes mellitus, and the main personal antecedent was previous bacterial infection in the prosthetic joint. At least one risk factor for fungal infection was present in 73% of the patients. There was no difference between the prevalence of infections caused by Candida albicans and non-albicans Candida species, and there was bacterial co-infection in 55% of the cases. DIAGNOSIS: For building up the case series, patients with cultures of bone and joint specimens that were positive for Candida species and had a clinical diagnosis of prosthetic joint infection were included in the case series. INTERVENTIONS: Surgical debridement with removal of the prosthesis was the most frequently used surgical approach (45%). All patients were treated with monotherapy, and the most frequently used antifungal agent was fluconazole. The total duration of antifungal therapy was 6 months in 73% of the cases. OUTCOMES: After the initial management, 73% of the patients achieved clinical remission. CONCLUSION: The most indicated initial management was debridement with removal of the prosthesis, and the most used treatment regimen was fluconazole monotherapy. The most prevalent treatment duration was 6 months. The initial management led to a favorable outcome in 73% of the cases. DESCRIPTORS: Prosthetic joint infection, Candida, treatment, and diagnosis.


Assuntos
Candida albicans/isolamento & purificação , Prótese Articular/microbiologia , Osteoartrite/cirurgia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/cirurgia , Coinfecção/epidemiologia , Comorbidade , Desbridamento/métodos , Feminino , Fluconazol/uso terapêutico , Humanos , Prótese Articular/efeitos adversos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/cirurgia , Osteoartrite/complicações , Prevalência , Infecções Relacionadas à Prótese/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
15.
J Mycol Med ; 30(2): 100967, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32321676

RESUMO

A 44-year-old woman, victim of a road accident in Mali was diagnosed with left knee arthritis. Joint effusion aspiration and subcutaneous surgical biopsies were positive for a melanized asexual ascomycete. Using microscopy and molecular biology, the fungus was identified as Curvularia sp. In vitro antifungal susceptibility was determined by the EUCAST broth microdilution reference technique and by E-test. The patient was treated with liposomal amphotericin B before posaconazole relay. Mycological samples obtained 10 days after starting the antifungal therapy by liposomal amphotericin B were negative in culture. Curvularia spp. are environmental fungi which can under certain conditions be pathogenic for humans.


Assuntos
Acidentes de Trânsito , Artrite Infecciosa/microbiologia , Ascomicetos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/microbiologia , Adulto , Antifúngicos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/imunologia , Ascomicetos/isolamento & purificação , Ascomicetos/fisiologia , Evolução Fatal , Feminino , França , Humanos , Imunocompetência , Traumatismos do Joelho/tratamento farmacológico , Traumatismos do Joelho/imunologia , Articulação do Joelho/microbiologia , Mali , Micoses/complicações , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/microbiologia , Quadriplegia/etiologia , Quadriplegia/microbiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/microbiologia , Doença Relacionada a Viagens
16.
PLoS One ; 15(4): e0231811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302369

RESUMO

The disease chytridiomycosis, caused by the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), has contributed to global amphibian declines. Bd infects the keratinized epidermal tissue in amphibians and causes hyperkeratosis and excessive skin shedding. In individuals of susceptible species, the regulatory function of the amphibian's skin is disrupted resulting in an electrolyte depletion, osmotic imbalance, and eventually death. Safe and effective treatments for chytridiomycosis are urgently needed to control chytrid fungal infections and stabilize populations of endangered amphibian species in captivity and in the wild. Currently, the most widely used anti-Bd treatment is itraconazole. Preparations of itraconazole formulated for amphibian use has proved effective, but treatment involves short baths over seven to ten days, a process which is logistically challenging, stressful, and causes long-term health effects. Here, we explore a novel anti-fungal therapeutic using a single application of the ionic liquid, 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-NTf2), for the treatment of chytridiomycosis. BMP-NTf2 was found be effective at killing Bd in vitro at low concentrations (1:1000 dilution). We tested BMP-NTf2 in vivo on two amphibian species, one that is relatively tolerant of chytridiomycosis (Pseudacris regilla) and one that is highly susceptible (Dendrobates tinctorius). A toxicity trial revealed a surprising interaction between Bd infection status and the impact of BMP-NTf2 on D. tinctorius survival. Uninfected D. tinctorius tolerated BMP-NTf2 (mean ± SE; 96.01 ± 9.00 µl/g), such that only 1 out of 30 frogs died following treatment (at a dose of 156.95 µL/g), whereas, a lower dose (mean ± SE; 97.45 ± 3.52 µL/g) was not tolerated by Bd-infected D. tinctorius, where 15 of 23 frogs died shortly upon BMP-NTf2 application. Those that tolerated the BMP-NTf2 application did not exhibit Bd clearance. Thus, BMP-NTf2 application, under the conditions tested here, is not a suitable option for clearing Bd infection in D. tinctorius. However, different results were obtained for P. regilla. Two topical applications of BMP-NTf2 on Bd-infected P. regilla (using a lower BMP-NTf2 dose than on D. tinctorius, mean ± SE; 9.42 ± 1.43 µL/g) reduced Bd growth, although the effect was lower than that obtained by daily doses of itracanozole (50% frogs exhibited complete clearance on day 16 vs. 100% for itracanozole). Our findings suggest that BMP-NTf2 has the potential to treat Bd infection, however the effect depends on several parameters. Further optimization of dose and schedule are needed before BMP-NTf2 can be considered as a safe and effective alternative to more conventional antifungal agents, such as itraconazole.


Assuntos
Antifúngicos/farmacologia , Anuros/microbiologia , Quitridiomicetos/efeitos dos fármacos , Imidas/farmacologia , Líquidos Iônicos/farmacologia , Pirrolidinas/farmacologia , Animais , Antifúngicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Imidas/uso terapêutico , Líquidos Iônicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Pirrolidinas/uso terapêutico , Pele/microbiologia , Esporos Fúngicos/efeitos dos fármacos
17.
Drug Discov Ther ; 14(2): 93-97, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32321877

RESUMO

The management of patients with brain abscess poses a significant challenge to clinicians in patients with chronic kidney disease. Obtaining a biopsy sample from the affected area is the mainstay in the diagnosis, but it is often unavailable. In most cases, therapy is guided by clinical findings and imaging alone. We discuss three cases of brain abscess- each with a different scenario and discuss the issues faced in management. The first case was a 32-year-old post-renal transplant male patient with a brain abscess due to dematiaceous fungi and was treated with amphotericin. The second case was a 42-year-old female patient with stage 5 chronic kidney disease on maintenance hemodialysis who presented with a brain abscess due to suspected fungal infection based on imaging findings and was managed with antibiotics and voriconazole. The third case was a 42-year-old post-renal transplant male patient who presented with a brain abscess due to nocardiosis and was managed with cotrimoxazole, meropenem and linezolid. We also summarize the approach to the management of brain abscess in resource-limited settings.


Assuntos
Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Infecções Bacterianas/tratamento farmacológico , Feminino , Humanos , Transplante de Rim , Linezolida/uso terapêutico , Masculino , Meropeném/uso terapêutico , Micoses/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Voriconazol/uso terapêutico
18.
Am J Ophthalmol ; 215: 1-7, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32171765

RESUMO

PURPOSE: To evaluate the utility of repeat cultures at days 3 and 7 after starting antifungal medications for predicting outcomes in fungal keratitis. DESIGN: Prespecified secondary analysis of the randomized clinical Mycotic Antimicrobial Localized Injection trial. METHODS: Patients presenting to Aravind Eye Hospital, Pondicherry, India, with fungal keratitis and visual acuity worse than 20/70 received topical natamycin and were randomized to either receive intrastromal injection of voriconazole or topical therapy alone. All subjects received corneal cultures at date of presentation, day 3, and day 7. Outcome measures included 3-week and 3-month visual acuity and scar size, corneal perforation, and/or the need for therapeutic penetrating keratoplasty (TPK). Visual acuity and scar size were analyzed with multiple linear regression controlling for baseline measures. Survival analysis was used to analyze the risk of corneal perforation and/or need for TPK. RESULTS: Of the 70 study subjects with fungal keratitis, 25 of 69 (36%) remained culture positive at day 3, and 20 of 62 (32%) were culture positive at day 7. Culture positivity at day 3 conferred a hazard ratio of 2.8 for requiring TPK (P = .03) but was not a statistically significant predictor of perforation, scar size, or final visual acuity. Culture positivity at day 7 had a hazard ratio of 3.5 for requiring TPK (P = .003). Those with positive cultures at day 7 had on average 3 logMAR lines worse visual acuity at 3 months (95% confidence interval 0.9 to 5.2 logMAR lines, P = .006) and 1.1 mm larger scar size at 3 months after controlling for baseline measures (95% confidence interval 0.1 to 2.2 mm; P = .03). CONCLUSIONS: While not as predictive as day 7 cultures, culture positivity at day 3 after starting treatment is a significant predictor of the need for TPK in patients with moderate-to-severe filamentous fungal keratitis. This has applications for risk stratification, and may facilitate earlier consideration of TPK in high-risk patients.


Assuntos
Antifúngicos/uso terapêutico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/microbiologia , Fungos/isolamento & purificação , Micoses/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perfuração da Córnea/diagnóstico , Substância Própria/efeitos dos fármacos , Úlcera da Córnea/tratamento farmacológico , Método Duplo-Cego , Infecções Oculares Fúngicas/tratamento farmacológico , Feminino , Humanos , Injeções Intraoculares , Ceratoplastia Penetrante , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Natamicina/uso terapêutico , Prognóstico , Fatores de Tempo , Acuidade Visual/fisiologia , Voriconazol/uso terapêutico , Adulto Jovem
19.
Rev. iberoam. micol ; 37(1): 5-16, ene.-mar. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-193840

RESUMO

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease


El factor de necrosis tumoral (TNF) es una citocina proinflamatoria involucrada en una amplia gama de procesos fisiológicos importantes y desarrolla un papel en la patogenia de algunas enfermedades. Los antagonistas del TNF (infliximab, adalimumab, etanercept) son efectivos en el tratamiento de afecciones inflamatorias. Los agentes biológicos antilinfocitarios (rituximab, alemtuzumab), los antagonistas de la integrina (natalizumab, etrolizumab y vedolizumab), de la interleucina 17A (secukinumab, ixekizumab) o los antagonistas de la IL-2 (daclizumab, basiliximab) se usan ampliamente después del trasplante y en trastornos gastroenterológicos, reumatológicos, dermatológicos, neurológicos y hematológicos. Dado el papel relevante de estos elementos de defensa del huésped contra agentes bacterianos, virales y fúngicos, el riesgo de infección durante el tratamiento con estos antagonistas genera preocupación. Las infecciones por hongos, tanto oportunistas como endémicos, se han asociado con estas terapias biológicas, pero la relación causal no está clara, especialmente entre los pacientes con un control deficiente de su enfermedad subyacente o que están recibiendo terapia con esteroides. Los pacientes en tratamiento con estos medicamentos deben ser examinados para detectar infecciones micóticas endémicas latentes. La profilaxis con cotrimoxazol podría ser útil para prevenir la infección por Pneumocystis jirovecii en pacientes mayores de 65 años que estén tomando antagonistas de TNF, agentes biológicos antilinfocitarios, o tengan linfopenia y estén en tratamiento concomitante con esteroides. Al igual que con otros fármacos inmunosupresores, deben suspenderse los antagonistas de TNF y los anticuerpos antilinfocitarios en pacientes con enfermedad infecciosa activa hasta su control


Assuntos
Humanos , Imunomodulação , Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Micoses/tratamento farmacológico , Fatores de Necrose Tumoral/antagonistas & inibidores , Terapia Biológica
20.
Biochim Biophys Acta Biomembr ; 1862(8): 183246, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142818

RESUMO

The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, ß-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.


Assuntos
Antifúngicos/química , Peptídeos Catiônicos Antimicrobianos/química , Proteínas Fúngicas/química , Micoses/tratamento farmacológico , Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Apoptose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Cisteína/genética , Proteínas Fúngicas/genética , Humanos , Lipídeos de Membrana/química , Micoses/genética , Micoses/microbiologia , Penicillium chrysogenum/química , Penicillium chrysogenum/genética
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