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[PMID]:29202140
[Au] Autor:Nawrot U; Sulik-Tyszka B; Kurzyk E; Mroczynska M; Wlodarczyk K; Wróblewska M; Basak GW; Brillowska-Dabrowska A
[Ad] Endereço:Department of Pharmaceutical Microbiology and Parasitology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland.
[Ti] Título:Relation of the polymorphism of cyp51A sequence and the susceptibility of Aspergillus fumigatus isolates to triazoles determined by commercial gradient test (Etest) and by reference methods.
[So] Source:Acta Biochim Pol;64(4):631-634, 2017.
[Is] ISSN:1734-154X
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to evaluate the accuracy of commercial gradient test (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates using reference microdilution methods and the analysis of sequences of the cyp 51A gene. The study was performed on twenty clinical isolates which were identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2 fragment of ribosomal DNA and the ß-tubulin gene, out of them seventeen isolates showed wild-type cyp51A sequence and three were positive for the mutation TR34/L98H. All isolates were tested for the susceptibility to itraconazole (ITZ), voriconazole (VOR) and posaconasole (POS) using microdilution methods, according to EUCAST and CLSI protocols, as well as using Etest. The results of microdilution and Etests were analysed separately according to clinical breakpoints (CBP) defined by EUCAST version 7.0 and epidemiological cut off values (ECV). Etest as well as reference methods excellently recognised the WT isolates, which were susceptible to all tested triazoles, regardless of the method and CBP or ECV criteria used. The Etest recognized three non-WT isolates as resistant or intermediately sensitive to ITZ and POS and one as resistant to VOR. The categorical concordance between Etests and EUCAST and Etests and the CLSI method ranged from 90 to 100%. The interpretation of the results obtained from routine A. fumigatus Etests requires great caution. The use of the confirmative examinations with reference AST methods as well as with molecular tests is recommended.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Aspergillus fumigatus/efeitos dos fármacos
Sistema Enzimático do Citocromo P-450/genética
Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos
Farmacorresistência Fúngica/efeitos dos fármacos
Proteínas Fúngicas/genética
[Mh] Termos MeSH secundário: Aspergillus fumigatus/genética
Farmacorresistência Fúngica/genética
Itraconazol/farmacologia
Testes de Sensibilidade Microbiana/métodos
Polimorfismo Genético
Triazóis/farmacologia
Voriconazol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungal Proteins); 0 (Triazoles); 304NUG5GF4 (Itraconazole); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.14.- (cytochrome P-450 CYP51A, Aspergillus); JFU09I87TR (Voriconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.18388/abp.2017_1571


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[PMID]:28989052
[Au] Autor:Matowane RG; Wieteska L; Bamal HD; Kgosiemang IKR; Van Wyk M; Manume NA; Abdalla SMH; Mashele SS; Gront D; Syed K
[Ad] Endereço:Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
[Ti] Título:In silico analysis of cytochrome P450 monooxygenases in chronic granulomatous infectious fungus Sporothrix schenckii: Special focus on CYP51.
[So] Source:Biochim Biophys Acta;1866(1):166-177, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sporotrichosis is an emerging chronic, granulomatous, subcutaneous, mycotic infection caused by Sporothrix species. Sporotrichosis is treated with the azole drug itraconazole as ketoconazole is ineffective. It is a well-known fact that azole drugs act by inhibiting cytochrome P450 monooxygenases (P450s), heme-thiolate proteins. To date, nothing is known about P450s in Sporothrix schenckii and the molecular basis of its resistance to ketoconazole. Here we present genome-wide identification, annotation, phylogenetic analysis and comprehensive P450 family-level comparative analysis of S. schenckii P450s with pathogenic fungi P450s, along with a rationale for ketoconazole resistance by S. schenckii based on in silico structural analysis of CYP51. Genome data-mining of S. schenckii revealed 40 P450s in its genome that can be grouped into 32 P450 families and 39 P450 subfamilies. Comprehensive comparative analysis of P450s revealed that S. schenckii shares 11 P450 families with plant pathogenic fungi and has three unique P450 families: CYP5077, CYP5386 and CYP5696 (novel family). Among P450s, CYP51, the main target of azole drugs was also found in S. schenckii. 3D modeling of S. schenckii CYP51 revealed the presence of characteristic P450 motifs with exceptionally large reductase interaction site 2. In silico analysis revealed number of mutations that can be associated with ketoconazole resistance, especially at the channel entrance to the active site. One of possible reason for better stabilization of itraconazole, compared to ketoconazole, is that the more extended molecule of itraconazole may form a hydrogen bond with ASN-230. This in turn may explain its effectiveness against S. schenckii vis-a-vis resistant to ketoconazole. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Antifúngicos/química
Sistema Enzimático do Citocromo P-450/química
Proteínas Fúngicas/química
Genoma Fúngico
Itraconazol/química
Sporothrix/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antifúngicos/farmacologia
Domínio Catalítico
Cristalografia por Raios X
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Farmacorresistência Fúngica/genética
Proteínas Fúngicas/antagonistas & inibidores
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Expressão Gênica
Seres Humanos
Itraconazol/farmacologia
Cetoconazol/química
Cetoconazol/farmacologia
Simulação de Acoplamento Molecular
Família Multigênica
Filogenia
Plantas/microbiologia
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Alinhamento de Sequência
Sporothrix/classificação
Sporothrix/efeitos dos fármacos
Sporothrix/genética
Esporotricose/tratamento farmacológico
Esporotricose/microbiologia
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungal Proteins); 304NUG5GF4 (Itraconazole); 9035-51-2 (Cytochrome P-450 Enzyme System); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171010
[St] Status:MEDLINE


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[PMID]:29388537
[Au] Autor:Carreira A; Ferreira JB; Pereira I; Ferreira J; Filipe P; Ferreira RB; Monteiro S
[Ad] Endereço:1​CEV, SA, Parque Industrial de Cantanhede/Biocant-Park, lote 120, 3060-197 Cantanhede, Portugal.
[Ti] Título:Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.
[So] Source:J Med Microbiol;67(2):198-207, 2018 Feb.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. METHODOLOGY: The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. RESULTS: We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. CONCLUSION: These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Arthrodermataceae/efeitos dos fármacos
Fungicidas Industriais/farmacologia
Malassezia/efeitos dos fármacos
Tinha dos Pés/tratamento farmacológico
Tinha Versicolor/tratamento farmacológico
[Mh] Termos MeSH secundário: Antifúngicos/uso terapêutico
Proteção de Cultivos
Descoberta de Drogas
Fluconazol/farmacologia
Fungicidas Industriais/uso terapêutico
Seres Humanos
Itraconazol/farmacologia
Testes de Sensibilidade Microbiana
Tinha dos Pés/microbiologia
Tinha Versicolor/microbiologia
Trichophyton/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungicides, Industrial); 304NUG5GF4 (Itraconazole); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000675


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[PMID]:29192424
[Au] Autor:Heras-Mosteiro J; Monge-Maillo B; Pinart M; Lopez Pereira P; Reveiz L; Garcia-Carrasco E; Campuzano Cuadrado P; Royuela A; Mendez Roman I; López-Vélez R
[Ad] Endereço:Department of Preventive Medicine and Public Health & Immunology and Microbiology, Rey Juan Carlos University, Avda. Atenas s/n, Alcorcón, Madrid, Spain, 28922.
[Ti] Título:Interventions for Old World cutaneous leishmaniasis.
[So] Source:Cochrane Database Syst Rev;12:CD005067, 2017 12 01.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.
[Mh] Termos MeSH primário: Antiprotozoários/uso terapêutico
Itraconazol/uso terapêutico
Leishmaniose Cutânea/terapia
Paromomicina/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Animais
Anti-Infecciosos/uso terapêutico
Antiprotozoários/administração & dosagem
Terapias Complementares/métodos
Crioterapia/métodos
Extremo Oriente
Feminino
Temperatura Alta/uso terapêutico
Seres Humanos
Itraconazol/administração & dosagem
Terapia a Laser
Leishmania major
Leishmania tropica
Masculino
Meia-Idade
Oriente Médio
Bases para Pomadas/administração & dosagem
Paromomicina/administração & dosagem
Fotoquimioterapia
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Antiprotozoal Agents); 0 (Ointment Bases); 304NUG5GF4 (Itraconazole); 61JJC8N5ZK (Paromomycin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD005067.pub5


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[PMID]:29310381
[Au] Autor:Liu X; Yang J; Ma W
[Ad] Endereço:Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
[Ti] Título:Primary cutaneous aspergillosis caused by Aspergillus.fumigatus in an immunocompetent patient: A case report.
[So] Source:Medicine (Baltimore);96(48):e8916, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Primary cutaneous aspergillosis in immunocompromised patients has been well described in extensive investigations. However, in immunocompetent hosts, primary cutaneous infection of aspergillus occurs rarely, and remains poorly characterized. PATIENT CONCERNS: We present a case of primary cutaneous aspergillosis manifested by erythematous plague covered with flava eschar. DIAGNOSES: The patient was diagnosed with primary cutaneous aspergillosis. INTERVENTIONS: Treatments with oral itraconazole at a dose of 75 mg/d and local wound care with ciclopirox olamine ointment were administered. OUTCOMES: After half a month, a partial resolution and a decrease in tenderness indicated gradual improvement, and a complete remission was achieved 2 months later. LESSONS: Primary cutaneous aspergillosis could occur in immunocompetent hosts. The initial lesions may appear in different forms, including macules, papules, nodules, or plaques. Repeated biopsy of a skin lesion for both culture and histopathology is needed.
[Mh] Termos MeSH primário: Aspergilose/tratamento farmacológico
Aspergillus fumigatus
Dermatomicoses/tratamento farmacológico
[Mh] Termos MeSH secundário: Antifúngicos/uso terapêutico
Criança
Dermatomicoses/patologia
Seres Humanos
Imunocompetência
Itraconazol/uso terapêutico
Masculino
Piridonas/uso terapêutico
Pele/efeitos dos fármacos
Pele/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Pyridones); 19W019ZDRJ (ciclopirox); 304NUG5GF4 (Itraconazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008916


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[PMID]:28450167
[Au] Autor:Berben P; Mols R; Brouwers J; Tack J; Augustijns P
[Ad] Endereço:Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, 3000 Leuven, Belgium.
[Ti] Título:Gastrointestinal behavior of itraconazole in humans - Part 2: The effect of intraluminal dilution on the performance of a cyclodextrin-based solution.
[So] Source:Int J Pharm;526(1-2):235-243, 2017 Jun 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) is known to enable absorption of the lipophilic drug itraconazole. Since the interaction between HP-ß-CD and itraconazole is characterized by a non-lineair, A -type phase-solubility diagram, the present study aimed to investigate the influence of intraluminal dilution (water intake) on the behavior and performance of an orally administered cyclodextrin-based solution of itraconazole. Subsequently, the in vivo behavior was simulated by combining in vitro dilution with permeation assessment. After the administration of a Sporanox solution to healthy volunteers with or without a glass of water, gastrointestinal and systemic concentrations of itraconazole were simultaneously monitored. Independently of the intake of water, no gastric precipitation of itraconazole was observed. After transfer to the duodenum, precipitation occurred and was more pronounced in the condition with water, resulting in a 7.6-fold reduction in duodenal AUC compared to the condition without water. Nevertheless, plasma concentration-time profiles did not demonstrate any significant differences in AUC , C and t . Application of freshly aspirated intestinal fluids on Caco-2 cells clearly confirmed that higher intestinal itraconazole concentrations after intake of Sporanox without water do not generate a substantially increased itraconazole uptake. A two-stage in vitro dilution test was combined with a permeation compartment to capture this solubility-permeability interplay. In conclusion, this work demonstrates that variations in intraluminal dilution may have a drastic impact on the gastrointestinal behavior of lipophilic drugs in the presence of cyclodextrins. In the case of an AP-type interaction with cyclodextrins, the trade-off between solubility and permeability may be affected.
[Mh] Termos MeSH primário: 2-Hidroxipropil-beta-Ciclodextrina/química
Portadores de Fármacos/química
Absorção Intestinal
Itraconazol/farmacocinética
[Mh] Termos MeSH secundário: Células CACO-2
Seres Humanos
Solubilidade
beta-Ciclodextrinas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (beta-Cyclodextrins); 1I96OHX6EK (2-Hydroxypropyl-beta-cyclodextrin); 304NUG5GF4 (Itraconazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


  7 / 5163 MEDLINE  
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Colombo, Arnaldo Lopes
Camargo, Zoilo Pires de
Texto completo SciELO Brasil
[PMID]:28746570
[Au] Autor:Shikanai-Yasuda MA; Mendes RP; Colombo AL; Queiroz-Telles F; Kono ASG; Paniago AMM; Nathan A; Valle ACFD; Bagagli E; Benard G; Ferreira MS; Teixeira MM; Silva-Vergara ML; Pereira RM; Cavalcante RS; Hahn R; Durlacher RR; Khoury Z; Camargo ZP; Moretti ML; Martinez R
[Ad] Endereço:Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
[Ti] Título:Brazilian guidelines for the clinical management of paracoccidioidomycosis.
[So] Source:Rev Soc Bras Med Trop;50(5):715-740, 2017 Sep-Oct.
[Is] ISSN:1678-9849
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Gerenciamento Clínico
Paracoccidioidomicose/tratamento farmacológico
Paracoccidioidomicose/patologia
[Mh] Termos MeSH secundário: Brasil
Consenso
Diagnóstico Diferencial
Seres Humanos
Itraconazol/uso terapêutico
América Latina
Paracoccidioides
[Pt] Tipo de publicação:JOURNAL ARTICLE; PRACTICE GUIDELINE
[Nm] Nome de substância:
0 (Antifungal Agents); 304NUG5GF4 (Itraconazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171218
[Lr] Data última revisão:
171218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE


  8 / 5163 MEDLINE  
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[PMID]:29016694
[Au] Autor:Galvão EL; Rabello A; Cota GF
[Ad] Endereço:Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
[Ti] Título:Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis.
[So] Source:PLoS One;12(10):e0186117, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Several controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis. METHODOLOGY: PRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as Google Scholar and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions. RESULTS: A total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57-70%) for all studies and 60% (CI95%: 50-70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43-77%) and 66% (CI95%: 58-73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50-98%) for L. mexicana; 88% for L. infantum (CI95%: 27-99%); 80% for L. donovani; 53% (CI95%: 29-76%) for L. major; 49% for L. braziliensis (CI95%: 21-78%); and 15% (CI95%: 1-84%) for L. tropica. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48-72%), 64% (CI95%: 44-80%) 65% (CI95%: 56-72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3-14%), 12% (CI95% 8-19%) and 13% (CI95%: 6-29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies. CONCLUSIONS: Available evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Azóis/uso terapêutico
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Mucocutânea/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Cutânea
Administração através da Mucosa
Antifúngicos/efeitos adversos
Azóis/efeitos adversos
Bases de Dados Factuais
Seres Humanos
Itraconazol/efeitos adversos
Itraconazol/uso terapêutico
Cetoconazol/efeitos adversos
Cetoconazol/uso terapêutico
Leishmaniose Cutânea/epidemiologia
Leishmaniose Cutânea/parasitologia
Leishmaniose Mucocutânea/epidemiologia
Leishmaniose Mucocutânea/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Azoles); 304NUG5GF4 (Itraconazole); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186117


  9 / 5163 MEDLINE  
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[PMID]:29016668
[Au] Autor:Won EJ; Choi MJ; Shin JH; Park YJ; Byun SA; Jung JS; Kim SH; Shin MG; Suh SP
[Ad] Endereço:Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
[Ti] Título:Diversity of clinical isolates of Aspergillus terreus in antifungal susceptibilities, genotypes and virulence in Galleria mellonella model: Comparison between respiratory and ear isolates.
[So] Source:PLoS One;12(10):e0186086, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We analyzed the antifungal susceptibility profiles, genotypes, and virulence of clinical Aspergillus terreus isolates from six university hospitals in South Korea. Thirty one isolates of A. terreus, comprising 15 respiratory and 16 ear isolates were assessed. Microsatellite genotyping was performed, and genetic similarity was assessed by calculating the Jaccard index. Virulence was evaluated by Galleria mellonella survival assay. All 31 isolates were susceptible to itraconazole, posaconazole, and voriconazole, while 23 (74.2%) and 6 (19.4%) showed amphotericin B (AMB) minimum inhibitory concentrations (MICs) of ≤ 1 mg/L and > 4 mg/L, respectively. Notably, respiratory isolates showed significantly higher geometric mean MICs than ear isolates to AMB (2.41 vs. 0.48 mg/L), itraconazole (0.40 vs. 0.19 mg/L), posaconazole (0.16 vs. 0.08 mg/L), and voriconazole (0.76 vs. 0.31 mg/L) (all, P <0.05). Microsatellite genotyping separated the 31 isolates into 27 types, but the dendrogram demonstrated a closer genotypic relatedness among isolates from the same body site (ear or respiratory tract); in particular, the majority of ear isolates clustered together. Individual isolates varied markedly in their ability to kill infected G. mellonella after 72 h, but virulence did not show significant differences according to source (ear or respiratory tract), genotype, or antifungal susceptibility. The current study shows the marked diversity of clinical isolates of A. terreus in terms of antifungal susceptibilities, genotypes and virulence in the G. mellonella model, and ear isolates from Korean hospitals may have lower AMB or triazole MICs than respiratory isolates.
[Mh] Termos MeSH primário: Aspergilose/genética
Aspergillus/efeitos dos fármacos
Farmacorresistência Fúngica/genética
Orelha/microbiologia
Sistema Respiratório/microbiologia
[Mh] Termos MeSH secundário: Animais
Antifúngicos/farmacologia
Aspergilose/tratamento farmacológico
Aspergilose/microbiologia
Aspergillus/patogenicidade
Orelha/patologia
Genótipo
Hospitais Universitários
Seres Humanos
Itraconazol/farmacologia
Lepidópteros/microbiologia
Repetições de Microssatélites/genética
Sistema Respiratório/patologia
Triazóis/farmacologia
Voriconazol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Triazoles); 304NUG5GF4 (Itraconazole); 6TK1G07BHZ (posaconazole); JFU09I87TR (Voriconazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186086


  10 / 5163 MEDLINE  
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[PMID]:28980793
[Au] Autor:Giovane RA; Manhas P; Gates K
[Ad] Endereço:University of Alabama, Tuscaloosa, AL
[Ti] Título:Itraconazole or Amphotericin B for Talaromycosis.
[So] Source:N Engl J Med;377(14):1402, 2017 10 05.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Anfotericina B
Itraconazol
[Mh] Termos MeSH secundário: Antifúngicos
Aspergilose
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Antifungal Agents); 304NUG5GF4 (Itraconazole); 7XU7A7DROE (Amphotericin B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1709123



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