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1.
Mycoses ; 65(2): 199-210, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34936143

RESUMO

BACKGROUND: Antifungal treatment duration and changes for invasive mould infections (IMI) have been poorly described. METHODS: We performed a 10-year cohort study of adult (≥18-year-old) allogeneic haematopoietic cell transplant recipients with proven/probable IMI to describe the duration and changes of antifungal treatment. All-cause-12-week mortality was described. RESULTS: Sixty-one patients with 66 IMI were identified. Overall treatment duration was 157 days (IQR: 14-675) and 213 (IQR: 90-675) days for patients still alive by Day 84 post-IMI diagnosis. There was at least one treatment change in 57/66 (86.4%) cases: median 2, (IQR: 0-6, range:0-8). There were 179 antifungal treatment changes due to 193 reasons: clinical efficacy (104/193, 53.9%), toxicity (55/193, 28.5%), toxicity or drug interactions resolution (15/193, 7.8%) and logistical reasons (11/193, 5.7%) and 15/193 (7.8%) changes due to unknown reasons. Clinical efficacy reasons included lack of improvement (34/104, 32.7%), targeted treatment (30/104, 28.8%), subtherapeutic drug levels (14/104, 13.5%) and other (26/104, 25%). Toxicity reasons included hepatotoxicity, nephrotoxicity, drug interactions, neurotoxicity and other in 24 (43.6%), 12 (21.8%), 12 (21.8%), 4 (7.4%) and 3 (5.5%) cases respectively. All-cause 12-week mortality was 31% (19/61), higher in patients whose antifungal treatment (logrank 0.04) or appropriate antifungal treatment (logrank 0.01) was started >7 days post-IMI diagnosis. All-cause 1-year mortality was higher in patients with ≥2 changes of treatment during the first 6 weeks post-IMI diagnosis (logrank 0.008) with an OR: 4.00 (p = .04). CONCLUSIONS: Patients with IMI require long treatment courses with multiple changes for variable reasons and potential effects on clinical outcomes, demonstrating the need more effective and safer treatment options. Early initiation of appropriate antifungal treatment is associated with improved outcomes.


Assuntos
Antifúngicos/uso terapêutico , Substituição de Medicamentos , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Transplantados , Adulto , Antifúngicos/classificação , Estudos de Coortes , Fungos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico
2.
Ann Hematol ; 99(7): 1429-1440, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32514626

RESUMO

With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.


Assuntos
Antifúngicos/uso terapêutico , Quimioprevenção/tendências , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Estaurosporina/análogos & derivados , Triazóis/uso terapêutico , Antifúngicos/classificação , Quimioprevenção/métodos , Interações Medicamentosas , Drogas em Investigação/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Estaurosporina/uso terapêutico
3.
Rev Soc Bras Med Trop ; 52: e20180480, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31340356

RESUMO

We report a rare case of subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana in an immunocompetent patient in Amazonas, Brazil. This dematiaceous fungus has been mainly associated with life-threatening infections affecting the central nervous systems of immunosuppressed patients. We present the clinical, laboratory, and therapeutic aspects, and in vitro susceptibility test results for different antifungal drugs. A brief review of the cases reported in the literature over the past 20 years has also been discussed. According to the literature review, the present case is the first report of subcutaneous phaeohyphomycosis due to C. bantiana in an immunocompetent patient in Latin America.


Assuntos
Ascomicetos/isolamento & purificação , Feoifomicose/diagnóstico , Feoifomicose/microbiologia , Antifúngicos/classificação , Antifúngicos/uso terapêutico , Biópsia , Brasil , Dermatomicoses/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Fungos Mitospóricos/isolamento & purificação , Feoifomicose/tratamento farmacológico , Feoifomicose/imunologia
4.
Molecules ; 24(4)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795596

RESUMO

This work reviews the new isolated cembranoid derivatives from species of the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016⁻2018. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton than in those belonging to the genera Lobophytum or Sinularia. Beyond the chemical composition, the biological properties were also reviewed, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. In spite of the biological activities detected in almost all samples, there is a remarkable diversity in the results which may be attributed to the chemical variability that needs to be deepened in order to develop new molecules with potential application in medicine.


Assuntos
Antozoários/química , Antibacterianos/química , Anti-Inflamatórios/química , Antifúngicos/química , Antineoplásicos/química , Diterpenos/química , Animais , Antozoários/metabolismo , Antibacterianos/classificação , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Inflamatórios/classificação , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antifúngicos/classificação , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antineoplásicos/classificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/classificação , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
5.
J Cyst Fibros ; 18(3): 364-367, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30638825

RESUMO

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in the domestic environment of patients at risk for aspergillosis. Here, we assessed the mother's and father's homes of an 18-year-old cystic fibrosis patient harbouring chronic colonisation with H285Y CYP51A azole-resistant isolate, in order to explore the link between environmental exposure and ARAF infection. In one dwelling, a very high overall contamination level was found (710-7.240 CFU/m3), with a predominance of A. fumigatus (640-6.490 CFU/m3), and ARAF showing the TR34/L98H mutation was isolated. Mycological follow-up of the patient showed the persistence of H285Y isolates, but no acquisition of TR34/L98H isolates was observed. This could be due to the low proportion of TR34/L98H isolates (<3%), or the establishment of preventative measures and dwelling remediation taken after the environmental investigation. Our data underlines the value of an environmental assessment to establish preventative measures and limit the risk of A. fumigatus exposure and ARAF acquisition.


Assuntos
Poluição do Ar em Ambientes Fechados , Antifúngicos , Aspergilose Broncopulmonar Alérgica , Aspergillus fumigatus , Azóis/farmacologia , Fibrose Cística , Adolescente , Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/prevenção & controle , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/classificação , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/etiologia , Aspergilose Broncopulmonar Alérgica/terapia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Farmacorresistência Fúngica , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Humanos , Masculino , Resultado do Tratamento
6.
J Cyst Fibros ; 18(2): 227-232, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30297214

RESUMO

Cystic fibrosis (CF) is characterised by chronic airway infection with bacteria and fungi. Infections caused by Scedosporium/Lomentospora species can occur and are difficult to treat. Moulds belonging to the genus Scedosporium/Lomentospora are detected most frequently in respiratory samples of patients with CF, next to Aspergillus spp. Our aim was to define pulmonary fungal infections due to Scedosporium/Lomentospora in CF and to study the antimycotic treatment. In this multicentre study (12 centres; duration January 2008 to December 2014) 31 patients with a lung infection caused by moulds of the genus Scedosporium/Lomentospora were included. 36 courses of antifungal treatment were documented. Scedosporium apiospermum sensu stricto accounted for 48.4% of cases. In 20/31 patients a therapeutic response under antimycotics (median duration 3.9 months) was achieved. Triple and double therapy was significantly more effective compared to monotherapy regarding FEV1, radiology, and symptoms. This data suggests that combined treatment is superior to monotherapy in patients with CF.


Assuntos
Antifúngicos , Fibrose Cística , Quimioterapia Combinada/métodos , Infecções Fúngicas Invasivas , Pneumopatias Fúngicas , Scedosporium , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/classificação , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Fibrose Cística/terapia , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Alemanha , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Testes de Função Respiratória/métodos , Scedosporium/efeitos dos fármacos , Scedosporium/isolamento & purificação , Tomografia Computadorizada por Raios X/métodos
7.
Rev. Soc. Bras. Med. Trop ; 52: e20180480, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1013305

RESUMO

Abstract We report a rare case of subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana in an immunocompetent patient in Amazonas, Brazil. This dematiaceous fungus has been mainly associated with life-threatening infections affecting the central nervous systems of immunosuppressed patients. We present the clinical, laboratory, and therapeutic aspects, and in vitro susceptibility test results for different antifungal drugs. A brief review of the cases reported in the literature over the past 20 years has also been discussed. According to the literature review, the present case is the first report of subcutaneous phaeohyphomycosis due to C. bantiana in an immunocompetent patient in Latin America.


Assuntos
Humanos , Masculino , Ascomicetos/isolamento & purificação , Feoifomicose , Feoifomicose/diagnóstico , Biópsia , Brasil , Hospedeiro Imunocomprometido , Dermatomicoses/tratamento farmacológico , Fungos Mitospóricos/isolamento & purificação , Feoifomicose/imunologia , Feoifomicose/tratamento farmacológico , Pessoa de Meia-Idade , Antifúngicos/classificação , Antifúngicos/uso terapêutico
9.
Rev. chil. infectol ; 35(4): 351-357, ago. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-978044

RESUMO

Resumen Introducción: El incremento de la enfermedad fúngica invasora (EFI) en pacientes inmunocomprometidos ha conducido a la frecuente prescripción de fármacos altamente activos pero de elevado costo económico. Objetivo: Caracterizar el uso de antifúngicos, evaluar su indicación y determinar consumo y costos asociados. Métodos: Estudio descriptivo, retrospectivo, desde enero de 2015 a abril de 2016. Auditoría de prescripciones y revisión de fichas clínicas; cada prescripción se clasificó de acuerdo a si correspondía a una EFI posible, probable o probada. Se calcularon consumos y costos de tratamientos. Resultados: Se auditaron 152 prescripciones de antifúngicos en 79 pacientes. El costo total de los medicamentos antifúngicos fue de US$ 714.413. El 52,1% del gasto (US $ 372.319) correspondió a indicaciones en EFI probada, 10,7% (US $ 76.377) EFI probable, 0.8% (US $ 5.638) no-EFI, 12,2% (US $ 87.459) EFI posibles y 1,5% (US $ 10.896) EFI descartada y 22,6% (US$ 161.723) fue profilaxis. El mayor consumo fue en indicaciones relacionadas a EFI probada con un DOT probada de 10,54 días, siendo anfotericina B liposomal y voriconazol iv los fármacos con mayor consumo con un DOTprobada AnBL de 3,15 y DOT probada voriconazol iv de 3,01. Conclusiones: El consumo de medicamentos antifúngicos genera altos costos correspondiente al 12% del presupuesto total de farmacia de nuestra institución. El gasto se asoció principalmente a indicaciones en EFI probadas, voriconazol y anfotericina B liposomal los con mayor consumo, lo que sumado a su alto costo y días prolongados de terapia generan un gran impacto en el presupuesto.


Background: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. Aim: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. Methods: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. Results: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. Conclusions: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Custos de Medicamentos , Infecções Fúngicas Invasivas/economia , Infecções Fúngicas Invasivas/tratamento farmacológico , Antifúngicos/economia , Antifúngicos/uso terapêutico , Chile , Estudos Retrospectivos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Infecções Fúngicas Invasivas/classificação , Hospitais Pediátricos , Antifúngicos/classificação
10.
Dev Comp Immunol ; 87: 90-97, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29894713

RESUMO

Drosomycin-type antifungal peptides (DTAFPs) are natural effectors of the innate immune system, which are restrictedly distributed in plants and ecdysozoans. Mehamycin is a bi-domain DTAFP (abbreviated as bDTAFP) firstly found in the Northern root-knot nematode Meloidogyne hapla. Here, we report its structural and functional features and the evolution of bDTAFPs in nematodes. Different from classical DTAFPs, mehamycin contains an insertion, called single Disulfide Bridge-linked Domain (abbreviated as sDBD), located in a loop region of the drosomycin scaffold. Despite this, recombinant mehamycin likely adopts a similar fold to drosomycin, as revealed by the circular dichroism spectral analysis. Functionally, it showed some weak activity against three species of fungi but relatively stronger activity against seven species of Gram-positive bacteria, indicative of functional diversification between mehamycin and classical DTAFPs. By computational data mining of the nematode databases, we identified polymorphic genes encoding mehamycin and a new multigene family of bDTAFPs (named roremycins) from Rotylenchulus reniformis. A combination of data suggests that the origination of sDBDs from M. hapla and R. reniformis is a consequence of convergent evolution, in which some probably suffered positive selection during evolution. Our study may be valuable in understanding the role of these unique antimicrobial peptides in the innate immunity of nematodes.


Assuntos
Antifúngicos/metabolismo , Proteínas de Helminto/química , Proteínas de Helminto/metabolismo , Nematoides/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Animais , Antifúngicos/classificação , Antifúngicos/farmacologia , Evolução Molecular , Fungos/classificação , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/efeitos dos fármacos , Proteínas de Helminto/genética , Modelos Moleculares , Nematoides/genética , Peptídeos/química , Peptídeos/genética , Filogenia , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Tylenchoidea/genética , Tylenchoidea/metabolismo
11.
Med Mycol ; 56(2): 197-206, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28525644

RESUMO

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.


Assuntos
Antifúngicos/uso terapêutico , Fungemia/complicações , Fungemia/tratamento farmacológico , Neoplasias Hematológicas/complicações , Idoso , Antifúngicos/classificação , Estudos de Casos e Controles , Feminino , Fungos/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Centros de Atenção Terciária , Resultado do Tratamento
12.
Curr Med Res Opin ; 34(7): 1209-1216, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28956459

RESUMO

BACKGROUND: Empirical antifungal therapy is effective in some patients with risk factors for invasive fungal disease (IFD) who do not qualify for the EORTC/MSG criteria for IFD, but who fail to respond to anti-bacterial and anti-viral therapy. OBJECTIVE: This retrospective single-center study investigated the epidemiology of IFD and empirical antifungal therapy in patients with hematological malignancies. METHODS: This study recruited 893 patients with hematologic malignancies who had failed to respond to anti-bacterial and anti-viral treatment and received antifungal therapy, but not for antifungal prophylaxis. Antifungal therapy regimens included amphotericin B, voriconazole, itraconazole and caspofungin. A total of 689 patients were diagnosed with proven, probable, or possible IFD, while 159 patients did not meet the EORTC/MSG criteria for IFD diagnosis but recovered with antifungal treatment, and 45 were excluded from having IFD. Effective treatment was defined as the disappearance or resolution of clinical symptoms of IFD. RESULTS: Patients diagnosed with IFD underwent chemotherapy at a higher proportion, and had significantly higher neutrophil counts compared to those who did not qualify for the EORTC/MSG criteria for IFD but responded to antifungals. The mortality due to all causes within 3 months was significantly higher for patients diagnosed with proven IFD, compared with those who did not qualify for the EORTC/MSG criteria for IFD. There was no discontinuation reported due to adverse events of caspofungin. CONCLUSION: Empirical antifungal treatment could help save the lives of some patients with severe infections who are strongly suspected of having IFD.


Assuntos
Antifúngicos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Hematológicas , Infecções Fúngicas Invasivas , Adulto , Idoso , Antifúngicos/classificação , China/epidemiologia , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Avaliação de Sintomas/métodos , Resultado do Tratamento
13.
Antonie Van Leeuwenhoek ; 110(2): 195-203, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27752797

RESUMO

A novel actinomycete strain, designated TRM 49605T, was isolated from a desert soil sample from Lop Nur, Xinjiang, north-west China, and characterised using a polyphasic taxonomic approach. The strain exhibited antifungal activity against the following strains: Saccharomyces cerevisiae, Curvularia lunata, Aspergillus flavus, Aspergillus niger, Fusarium oxysporum, Penicillium citrinum, Candida albicans and Candida tropicalis; Antibacterial activity against Bacillus subtilis, Staphylococcus epidermidis and Micrococcus luteus; and no antibacterial activity against Escherichia coli. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain TRM 49605T to the genus Streptomyces. Strain TRM 49605T shows high sequence similarities to Streptomyces roseolilacinus NBRC 12815T (98.62 %), Streptomyces flavovariabilis NRRL B-16367T (98.45 %) and Streptomyces variegatus NRRL B-16380T (98.45 %). Whole cell hydrolysates of strain TRM 49605T were found to contain LL-diaminopimelic acid as the diagnostic diamino acid and galactose, glucose, xylose and mannose as the major whole cell sugars. The major fatty acids in strain TRM 49605T were identified as iso C16:0, anteiso C15:0, C16:0 and Summed Feature 5 as defined by MIDI. The main menaquinones were identified as MK-9(H4), MK-9(H6), MK-9(H8) and MK-10(H6). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylinositol mannoside. The G+C content of the genomic DNA was determined to be 71.2 %. The DNA-DNA relatedness between strain TRM 49605T and the phylogenetically related strain S. roseolilacinus NBRC 12815T was 60.12 ± 0.06 %, which is lower than the 70 % threshold value for delineation of genomic prokaryotic species. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain TRM 49605T (=CCTCC AA2015026T = KCTC 39666T) should be designated as the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces luozhongensis sp. nov. is proposed.


Assuntos
Streptomyces/classificação , Streptomyces/fisiologia , Antibacterianos/classificação , Antibacterianos/metabolismo , Antifúngicos/classificação , Antifúngicos/metabolismo , Bactérias , Composição de Bases/genética , DNA Bacteriano/genética , Fungos/crescimento & desenvolvimento , Filogenia , RNA Ribossômico 16S/genética , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Streptomyces/genética , Streptomyces/metabolismo
14.
Dtsch Med Wochenschr ; 141(24): 1752-1756, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-27903025

RESUMO

The incidence of life threatening invasive fungal infections in patients with hematological malignancies during intensive chemotherapy or after hematopoetic stem cell transplantation, patients after solid organ transplantation, ICU patients and premature infants is rising. Mortality rates of invasive fungal infections, caused by Aspergillus species or mucormycetes, may reach 100%, in spite of considerable progress in diagnosis, antifungal prophylaxis and therapy. Comprehensive, profound knowledge of specific diagnostic and current treatment algorithms is essential to improve the prognosis of patients suffering from systemic fungal infections; this article encompasses recent developments in the field of antifungal treatment.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/classificação , Micologia/métodos , Micologia/tendências , Micoses/diagnóstico , Micoses/tratamento farmacológico , Medicina Baseada em Evidências , Humanos , Micoses/classificação , Resultado do Tratamento
15.
Expert Opin Drug Metab Toxicol ; 12(6): 645-55, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27111148

RESUMO

INTRODUCTION: Despite the increased availability of systemic antifungal agents in recent years, the management of invasive fungal disease is still associated with significant morbidity and mortality. Knowledge of a drug's pharmacokinetic behavior is critical for optimizing existing treatment strategies. AREAS COVERED: This review examines the pharmacokinetics of the major drug classes used to treat invasive mycoses including the echinocandins, imidazoles, triazoles, nucleoside analogs, and polyenes. It examines the mechanisms behind dose-exposure profiles that differ in children as compared with adults and explores the utility of pharmacogenetic testing and therapeutic drug monitoring. EXPERT OPINION: Lifesaving medical advances for oncologic and autoimmune conditions have resulted in a significant increase in the frequency of opportunistic fungal infections. Owing to the high rate of treatment failures observed when managing invasive fungal infections, strategies to optimize antifungal therapy are critical when caring for these complex patients. Opportunities to maximize positive outcomes include dose refinement based on age or genetic status, formulation selection, co-administration of interacting medications, and administration with regard to food. The application of therapeutic drug monitoring for dose individualization is a valuable strategy to achieve pharmacodynamic targets.


Assuntos
Antifúngicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Infecções Fúngicas Invasivas/tratamento farmacológico , Adulto , Fatores Etários , Antifúngicos/classificação , Antifúngicos/farmacocinética , Criança , Relação Dose-Resposta a Droga , Humanos , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Farmacogenética/métodos
16.
Med Chem ; 12(8): 795-800, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26924627

RESUMO

BACKGROUND: Fungi are an emerging threat in medicine and agriculture and current therapeutics have proved to be insufficient and toxic. This has led to an increased interest in peptide-based therapeutics, especially antifungal peptides (AFPs), being safer and more effective drug candidates against fungal threats. However, screening for peptides with antifungal activity is costly and timeconsuming. However, by using computational techniques, we can overcome these restricting factors. The aim of the present study is to compare different machine learning algorithms in combination with Chou's pseudo amino acid composition in classifying and predicting AFPs to represent a precise model for AFP prediction. METHODS: Five different machine learning algorithms frequently used for classification of biological data were used and their performance was evaluated and compared based on their accuracy, sensitivity, specificity and Matthew's correlation coefficient. The two algorithms with the best performance were then further verified with an independent test dataset. RESULTS: SVM and Bagged-C4.5 classifiers had the highest performance results among the five algorithms. Further validations showed that the model generated using SVM can be employed for precise classification and prediction of antifungal peptides. All the performance values of this model were above 80%, making the classifier highly accurate and trustable. CONCLUSION: Using computational approaches, especially data mining techniques, we can develop a precise prediction model for antifungal peptides. The model developed in this study using SVM can be considered a powerful tool for the prediction of antifungal peptides, which can be the first step in synthesis and discovery of novel fungi targeting agents.


Assuntos
Algoritmos , Antifúngicos/classificação , Aprendizado de Máquina , Peptídeos/classificação
17.
Rev. bras. plantas med ; 18(2,supl.1): 605-612, 2016. tab, graf
Artigo em Português | LILACS | ID: biblio-830058

RESUMO

RESUMO O objetivo deste trabalho foi avaliar a atividade antifúngica de óleos essenciais e vegetais no controle in vitro de Colletotrichum gloeosporioides, agente causal da antracnose em pós-colheita de frutíferas. Treze óleos essenciais foram utilizados em concentrações de 0,00%, 0,40%, 0,80%, 1,70%, 3,20%, 6,25%, 12,50%, 25,00%, 50,00% e 100,00%, e uma linhagem padrão de Colletotrichum gloeosporioides. Foram avaliadas a concentração inibitória mínima e a concentração mínima fungicida a fim de caracterizar o potencial de cada um dos óleos essenciais avaliados. Verificou-se que os óleos utilizados apresentaram atividade fungicida em diferentes concentrações, as quais variaram de 0,80% (melaleuca), 3,20%, (eucalipto), 6,25% (limão, capim limão, cravo da índia, canela e nim), 12,5% (hortelã e citronela), 25% (copaíba), 50% (coco e gengibre) e 100% (manjericão). O óleo de nim apresentou maior redução da carga microbiana em função do tempo de exposição, sendo necessários 30 minutos para anulação da contagem microbiana. O efeito antifúngico dos óleos essenciais, para controle de Colletotrichum gloeosporioides, depende da planta e da concentração empregada.


ABSTRACT This study aimed to evaluate the antifungal effect of essential and vegetal oils in the in vitro control of Colletotrichum gloeosporioides, a causal agent of anthracnose in fruit postharvest. Thirteen essential oils were used at concentrations of 0.00%, 0.40%, 0.80%, 1.70%, 3.20%, 6.25%, 12.50%, 25.00%, 50.00%, and 100.00%, and also a standard strain of Colletotrichum gloeosporioides, The minimum inhibitory concentration and minimum fungicidal concentration were assessed to characterize the potential of each of the essential oils tested. We found that used oils showed fungicidal activity at different concentrations, which varied in 0.80% (Melaleuca alternifólia), 3.20%, (Eucalyptus globulus), 6.25% (Citrus limonium, Cymbopogon citratus, Syzygium aromaticum, Cinnamomum zeylanicum, and Azadirachta indica), 12.5% (Mentha piperita and Cymbopogon winterianus), 25% (Copaifera langsdorfii), 50% (Cocos nucifera and Zingiber officinale), and 100% (Ocimum basilicum). The Azadirachta indica oil showed greater reduction of microbial load because of the exposure time, and took 30 minutes for annulment of microbial count. The antifungal effect of essential oils to control Colletotrichum gloeosporioides depends on the plant and quantity of concentration.


Assuntos
Plantas/classificação , Técnicas In Vitro/classificação , Óleos Voláteis/análise , Colletotrichum/fisiologia , Plantas Medicinais/classificação , Antifúngicos/classificação
18.
Rev Iberoam Micol ; 31(4): 249-54, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-25434346

RESUMO

Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper.


Assuntos
Fungemia/etiologia , Doenças Hematológicas/complicações , Antifúngicos/classificação , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/etiologia , Aspergilose/prevenção & controle , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Fungemia/diagnóstico , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Fungemia/microbiologia , Fungemia/prevenção & controle , Doenças Hematológicas/imunologia , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hospedeiro Imunocomprometido , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Mucormicose/microbiologia , Fatores de Risco , Scedosporium/isolamento & purificação
19.
Rev. bras. plantas med ; 16(3): 539-544, jul.-set. 2014. tab
Artigo em Inglês | LILACS | ID: lil-722274

RESUMO

Generally, the medicinal plants have antifungal substances that can be used for the plant protection against phytopathogens. The objective of this study was to know the efficiency of aqueous extracts from medicinal plants against the major etiological agents of coffee tree. The aqueous extracts used were extracted from bulbs of Allium sativum, leaves of Vernonia polysphaera, Cymbopogon citratus, Cymbopogon nardus, Cordia verbenacea, Eucalyptus citriodora, Ricinus communis, Azadirachta indica, Piper hispidinervum and flower buds of Syzygium aromaticum. The etiological agents considered for this study were Cercospora coffeicola, Colletotrichum gloeosporioides, Fusarium oxysporum, Phoma tarda, Rhizoctonia solani and Hemileia vastatrix. The screening for harmful extracts was done based on mycelial growth and conidial germination inhibition. All experiments performed were in vitro conditions. The inhibition of mycelial growth was performed mixing the extracts with the PDA. This mixture was poured in Petri dishes. On the center of the dishes was added one PDA disc with mycelium. It was incubated in a chamber set to 25ºC. The evaluation was done daily by measuring the mycelial growth. The germination assessment was also performed with Petri dishes containing agar-water medium at 2%. These were incubated at 25ºC for 24 hours. After this period the interruption of germination was performed using lactoglycerol. The experiments were conducted in a completely randomized design. The most effective plant extracts against the micelial growth and conidial germination were V. polysphaera, S. aromaticum and A. sativum.


Geralmente, as plantas medicinais têm substâncias antifúngicas que podem ser utilizadas para a proteção das plantas contra fitopatógenos. O objetivo deste estudo foi conhecer a eficiência de extratos aquosos de plantas medicinais contra os principais agentes etiológicos do cafeeiro. Os extratos aquosos utilizados foram extraídos de bulbos de Allium sativum, folhas de Vernonia polysphaera, Cymbopogon citratus, Cymbopogon nardus, Cordia verbenacea, Eucalyptus citriodora, Ricinus communis, Azadirachta indica, Piper hispidinervum e botões florais de Syzygium aromaticum. Os agentes etiológicos considerados neste estudo foram Cercospora coffeicola, Colletotrichum gloeosporioides, Fusarium oxysporum, Phoma tarda, Rhizoctonia solani e Hemileia vastatrix. A triagem dos extratos foi realizada com base no crescimento micelial e na inibição da germinação de conídios. Todos os experimentos foram realizados em condições in vitro. A inibição do crescimento micelial foi realizada misturando-se os extratos com PDA. Esta mistura foi vertida em placas de Petri. No centro das placas foi adicionado um disco de PDA com micélio. Incubou-se em câmara programada para 25°C. A avaliação foi feita diariamente através da medição do crescimento micelial. O experimento sobre a germinação também foi realizado com placas com meio ágar-água a 2%. Estas foram incubadas durante 24 horas. Após este período, a interrupção da germinação foi realizada utilizando lactoglicerol. Os experimentos foram conduzidos em delineamento inteiramente casualizado. Os extratos de plantas mais eficazes contra o crescimento micelial e germinação de conídios foram V. polysphaera, S. aromaticum e A. sativum.


Assuntos
Plantas Medicinais/efeitos adversos , Extratos Vegetais/análise , Coffea/metabolismo , Antifúngicos/classificação , Controle de Pragas/instrumentação
20.
Mikrobiyol Bul ; 46(4): 707-15, 2012 Oct.
Artigo em Turco | MEDLINE | ID: mdl-23188586

RESUMO

Trichosporon species cause systemic, mucosa associated and superficial infections which include white piedra. Disseminated fungal infections due to Trichosporon species have increased in the recent years. Hematologic malignancy, cytotoxic chemotherapy, and organ transplantation are the main risk factors for disseminated Trichosporon infections. Two most common species that cause the disseminated Trichosporon infections are Trichosporon asahii and Trichosporon mucoides. Diagnosis and treatment of Trichosporon infections are difficult. Invasive trichosporonosis caused by T.asahii has a high mortality rate and a very poor prognosis. Fungicidal activity of amphotericin B against T.asahii isolates is inadequate. For echinocandin group of drugs, high minimum inhibitory concentration (MIC, µg/ml) values are obtained. Currently, triazole antifungal agents are the preferred drugs for the treatment of Trichosporon infections. In this review article general characteristics of T.asahii and its infections were summarized.


Assuntos
Trichosporon/classificação , Tricosporonose/microbiologia , Antifúngicos/classificação , Antifúngicos/uso terapêutico , Citotoxinas/uso terapêutico , Neoplasias Hematológicas/complicações , Humanos , Transplante de Órgãos/efeitos adversos , Piedra/microbiologia , Prognóstico , Fatores de Risco , Trichosporon/efeitos dos fármacos , Trichosporon/patogenicidade , Tricosporonose/diagnóstico , Tricosporonose/epidemiologia , Tricosporonose/terapia
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