RESUMO
BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.
Assuntos
Infecções por HIV , Hipertermia Induzida , Sporothrix , Esporotricose , Adulto , Humanos , Masculino , Esporotricose/tratamento farmacológico , Esporotricose/patologia , Itraconazol/uso terapêutico , Itraconazol/farmacologia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
INTRODUCTION: There is an epidemic emergence of increased resistance in dermatophytes with to antifungal drugs with ergosterol1 (Erg1) and Erg11 mutations to terbinafine and azoles. Apart from mutations, mechanisms that predict clinical failure include efflux pumps, cellular kinases, heat shock proteins (Hsp), and biofilms. Apart from itraconazole and SUBATM (Super-Bioavailable) itraconazole, measures that can be used in terbinafine failure include efflux-pump inhibitors, Hsp inhibitors and judicious use of antifungal drugs (topical + systemic) combinations. AREAS COVERED: A PubMed search was done for the relevant studies and reviews published in the last 22 years using keywords dermatophytes OR Trichophyton, anti-fungal, resistance, mechanism and fungal AND resistance mechanisms. Our aim was to look for literature on prevalent species and we specifically researched studies on Trichophyton genus. We have analyzed varied antifungal drug mechanisms and detailed varied experimental and approved drugs to treat recalcitrant dermatophytosis. EXPERT OPINION: Apart from administering drugs with low minimum inhibitory concentration, combinations of oral and topical antifungals (based on synergy data) and new formulations of existing drugs are useful in recalcitrant cases. There is a need for research into resistance mechanism of the existent Trichophyton strains in therapeutic failures in tinea corporis & cruris instead of data derived from laboratory strains which may not mirror clinical failures.
Assuntos
Arthrodermataceae , Tinha , Humanos , Antifúngicos , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Trichophyton/genética , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Tinha/tratamento farmacológico , Tinha/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Sporotrichosis caused by Sporothrix brasiliensis is a global emergent infectious disease. Due to the scarcity of therapeutic options for fungal diseases, new antifungals are urgently needed. Nikkomycin Z (NikZ) is a future option as an agent against dimorphic fungi. We evaluated NikZ monotherapy and in combination with itraconazole (ITZ; the conventional therapy) in the treatment of experimental sporotrichosis caused by S. brasiliensis in a murine model. Animals were subcutaneously infected, and treated orally for 30 days. The study groups were as follows control (untreated), ITZ group (50 mg/kg/day), and three groups treated with NikZ, two by monotherapy (200 or 400 mg/kg/day), and one combining NikZ (400 mg/kg/day) and ITZ. Efficacy of treatments was evaluated via body weight gain, mortality and fungal burden in tissues. Efficacy was noted in all treatment groups, and the group receiving the drug combination showed even better results than those with monotherapy. Our study shows for the first time the high potential of NikZ to be used in the treatment of sporotrichosis caused by S. brasiliensis.
Assuntos
Sporothrix , Esporotricose , Animais , Camundongos , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia , Testes de Sensibilidade Microbiana , Itraconazol/uso terapêutico , Antifúngicos/uso terapêuticoRESUMO
BACKGROUND: Recalcitrant dermatophyte infections are being reported from various parts of the world due to varied causes including strain variation, steroid misuse, SQLE mutations, and variable quality of itraconazole pellet formulations. The oral drug preferred in endemic areas is itraconazole, to which MIC levels remain low, and clinical failures to itraconazole reported defy a sound scientific explanation. OBJECTIVES: The objective of the study was to conduct a proteomic and genomic analysis on isolates from therapeutically recalcitrant case with isolation of gene mutations and enzymatic abnormalities to explain azole failures. METHODS: Trichophyton mentagrophyte interdigitale complex strains were isolated from seven clinically non-responding tinea corporis/cruris patients, who had failed a sequential course of 6 weeks of terbinafine 250 mg QD and itraconazole 100 mg BID. After AFST 1 strain, KA01 with high MIC to most drugs was characterized using whole genome sequencing, comparative proteomic profiling, and total sterol quantification. RESULTS: Sterol quantification showed that the standard strain of Trichophyton mentagrophytes (MTCC-7687) had half the ergosterol content than the resistant KA01 strain. Genomic analysis revealed mutations in SQLE, ERG4, ERG11, MDR1, MFS genes, and a novel ERG3 mutation. Proteomic analysis established the aberrant expression of acetyl Co-A transferase in the resistant strain and upregulation of thioredoxin reductase and peroxiredoxin. CONCLUSION: Our findings demonstrate possible reasons for multidrug resistance in the prevalent strain with mutations in genes that predict terbinafine (SQLE) and azole actions (ERG4, ERG11, ERG3) apart from efflux pumps (MDR1, MFS) that can explain multidrug clinical failures.
Assuntos
Antifúngicos , Tinha , Humanos , Terbinafina/uso terapêutico , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Itraconazol/uso terapêutico , Proteômica , Trichophyton/genética , Tinha/tratamento farmacológico , Tinha/epidemiologia , Mutação , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana , Regulador Transcricional ERG/genéticaRESUMO
Sporotrichosis is a neglected and emerging mycosis caused by the traumatic implantation of Sporothrix propagules into the (sub)cutaneous tissues of humans and animals. We evaluated canine sporotrichosis's clinical-therapeutic, epidemiological profile, and in vitro susceptibility of isolates to itraconazole. The variables were evaluated by a chi-square test. A total of 69 dogs were infected with Sporothrix spp., and the molecular identification revealed an overwhelming occurrence of S. brasiliensis as the etiological agent. The epidemiological profile was male (56.5%), adults (4.9 ± 1.92 years old; 69.6%), and mongrels (53.6%). The clinical signs were 76.8%, ulcers, draining tracts, and nodules were predominant, mainly in the nasal region (82.2%). Dogs were diagnosed late with an evolution time of up to 3 months (34.8%). According to the prior therapeutic information, 52.2% received empirical therapy, 79.2% antibiotics, and had a 0.29 significantly greater chance of presenting lesion evolution time Ë 3 months (P < .05; Odds Ratio [OR] 1/0.29). Additionally, 25 S. brasiliensis isolates recovered between 2006-2012 (n = 15; Minimal inhibitory concentration (MIC): 0.06-2 µg/ml) and 2013-2018 (n = 10; MIC: 2â16 µg/ml) were tested against itraconazole (ITZ). These findings highlighted the resistance to ITZ in clinical cases due to S. brasiliensis occurring after 2013, showing the temporal evolution of ITZ-resistance. We warn of the importance of accurate and early diagnosis in Sporothrix-affected areas, and we report the emergence of ITZ-resistant isolates in Southern Brazil.
Sporotrichosis is a fungal zoonosis. We investigated the clinical-therapeutic, epidemiological profile, and in vitro susceptibility of isolates to itraconazole (ITZ) in canine cases in Southern Brazil. Our study highlighted the emergence of ITZ-resistant Sporothrix brasiliensis and the main challenges for clinical control of this neglected disease.
Assuntos
Doenças do Cão , Sporothrix , Esporotricose , Humanos , Cães , Masculino , Animais , Esporotricose/tratamento farmacológico , Esporotricose/epidemiologia , Esporotricose/veterinária , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Testes de Sensibilidade Microbiana/veterinária , Brasil/epidemiologia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologiaRESUMO
BACKGROUND: Fusarium species are saprophytic fungi with a worldwide distribution. These fungi cause various infections among immunocompromised patients; however, they can also involve immunocompetent individuals. CASE PRESENTATION: We report a case of a 41-year-old Iranian woman who presented with ulcerative lesions on her lips 10 months ago. She had a long history of anxiety but had no history of classical risk factors such as trauma, cosmetic lip tattoo, burning in her lips, smoking or use of alcohol and opium. A skin biopsy from the lower lip was performed and sent for microbiological examinations. Hyaline septate hyphae were seen on direct microscopy with potassium hydroxide. The clinical specimen was subcultured on sabouraud dextrose agar with chloramphenicol and prepared for antifungal susceptibility testing and molecular identification. Considering the minimum inhibitory concentrations (MIC) for antifungals, itraconazole (100 mg orally twice a day) was started for her, and after 2 months, the lesions were treated. She followed up for 3 months, and no signs of disease recurrence were observed. CONCLUSIONS: Selecting an appropriate treatment strategy according to the laboratory assessments is essential in clinical practice and the management of rare infections to prevent related mortality and morbidity of opportunistic fungal infections.
Assuntos
Fusarium , Itraconazol , Adulto , Ágar , Antifúngicos/uso terapêutico , Cloranfenicol , Feminino , Glucose , Humanos , Irã (Geográfico) , Itraconazol/uso terapêutico , Lábio , Ópio , Úlcera/tratamento farmacológicoRESUMO
Chronic topical cases of Sporotrichosis, a chronic fungal infection caused by the ubiquitously present cryptic members of the Sporothrix species complex, are treated with oral administrations of itraconazole. However, severe pulmonary or disseminated cases require repeated intra-venous doses of amphotericin B or even surgical debridement of the infected tissue. The unavoidable adverse side-effects of the current treatments, besides the growing drug resistance among Sporothrix genus, demands exploration of alternative therapeutic options. Medicinal herbs, due to their multi-targeting capacity, are gaining popularity amidst the rising antimicrobial recalcitrance. Withania somnifera is a well-known medicinal herb with reported antifungal activities against several pathogenic fungal genera. In this study, the antifungal effect of the whole plant extract of W. somnifera (WSWE) has been explored for the first time, against an itraconazole resistant strain of S. globosa. WSWE treatment inhibited S. globosa yeast form growth in a dose-dependent manner, with IC50 of 1.40 mg/ml. Minimum fungicidal concentration (MFC) was found to be 50 mg/ml. Sorbitol protection and ergosterol binding assays, revealed that anti-sporotrichotic effects of WSWE correlated well with the destabilization of the fungal cell wall and cell membrane. This observation was validated through dose-dependent decrease in overall ergosterol contents in WSWE-treated S. globosa cells. Compositional analysis of WSWE through high performance liquid chromatography (HPLC) exhibited the presence of several anti-microbial phytochemicals like withanone, withaferin A, withanolides A and B, and withanoside IV and V. Withanone and withaferin A, purified from WSWE, were 10-20 folds more potent against S. globosa than WSWE, thus, suggesting to be the major phytocompounds responsible for the observed anti-sporotrichotic activity. In conclusion, this study has demonstrated the anti-sporotrichotic property of the whole plant extract of W. somnifera against S. globosa that could be further explored for the development of a natural antifungal agent against chronic Sporotrichosis.
Assuntos
Plantas Medicinais , Sporothrix , Esporotricose , Withania , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Saccharomyces cerevisiae , Esporotricose/microbiologia , Withania/químicaRESUMO
Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.
Assuntos
Terapias Complementares , Fármacos Dermatológicos , Dermatoses do Pé , Onicomicose , Humanos , Onicomicose/tratamento farmacológico , Antifúngicos/uso terapêutico , Terbinafina/uso terapêutico , Itraconazol/uso terapêutico , Voriconazol/uso terapêutico , Dermatoses do Pé/tratamento farmacológico , Naftalenos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Resultado do TratamentoAssuntos
Uso Off-Label , Dermatopatias/tratamento farmacológico , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Colchicina/farmacologia , Colchicina/uso terapêutico , Dapsona/farmacologia , Dapsona/uso terapêutico , Dermatologia , Humanos , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Losartan/farmacologia , Losartan/uso terapêutico , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Ondansetron/farmacologia , Ondansetron/uso terapêutico , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Tetraciclinas/farmacologia , Tetraciclinas/uso terapêutico , Talidomida/farmacologia , Talidomida/uso terapêutico , Ácido Tranexâmico/farmacologia , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. METHODS: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. FINDINGS: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. INTERPRETATION: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.
Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Itraconazol/farmacologia , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/uso terapêutico , COVID-19/etiologia , COVID-19/transmissão , Chlorocebus aethiops , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacocinética , Itraconazol/uso terapêutico , Masculino , Mesocricetus , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudo de Prova de Conceito , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento , Células VeroRESUMO
BACKGROUND: Infectious keratitis is the main cause of preventable blindness worldwide, with about 1.5-2.0 million new cases occurring per year. This inflammatory response may be due to infections caused by bacteria, fungi, viruses or parasites. Fungal keratitis is a poorly studied health problem. OBJECTIVES: This study aimed to identify a new fungal species by molecular methods and to explore the possible efficacy of the three most common antifungals used in human keratitis in Mexico by performing in vitro analysis. The capacity of this pathogen to cause corneal infection in a murine model was also evaluated. METHODS: The fungal strain was isolated from a patient with a corneal ulcer. To identify the fungus, taxonomic and phylogenetic analyses (nrDNA ITS and LSU data set) were performed. An antifungal susceptibility assay for amphotericin B, itraconazole and voriconazole was carried out. The fungal isolate was used to develop a keratitis model in BALB/c mice; entire eyes and ocular tissues were preserved and processed for histopathologic examination. RESULTS AND CONCLUSION: This fungal genus has hitherto not been reported with human keratitis in Mexico. We described a new species Purpurecillium roseum isolated from corneal infection. P roseum showed resistance to amphotericin B and itraconazole and was sensitive to voriconazole. In vivo study demonstrated that P roseum had capacity to developed corneal infection and to penetrate deeper corneal tissue. The global change in fungal infections has emphasised the need to develop better diagnostic mycology laboratories and to recognise the group of potential fungal pathogens.
Assuntos
Antifúngicos/uso terapêutico , Hypocreales/classificação , Hypocreales/efeitos dos fármacos , Hypocreales/isolamento & purificação , Ceratite/microbiologia , Idoso , Anfotericina B/uso terapêutico , Animais , Córnea , DNA Fúngico , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Humanos , Hypocreales/patogenicidade , Itraconazol/uso terapêutico , Ceratite/tratamento farmacológico , Ceratite/patologia , México , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Técnicas de Tipagem Micológica , Micoses/tratamento farmacológico , Micoses/microbiologia , Filogenia , Voriconazol/uso terapêuticoRESUMO
The treatment of feline sporotrichosis is a challenge for veterinary clinicians since refractory cases may occur, due either to patient and/or to pharmacological management errors or due to the development of antifungal resistance. Thus, we aimed to describe the therapeutic history of feline cases infected by itraconazole-resistant Sporothrix brasiliensis in an endemic region of Southern Brazil. Medical records of cats attended at the Veterinary Clinic Hospital (Pelotas/RS, Brazil) between 2016 and 2017 were reviewed. Twelve cases of infection by S. brasiliensis with that showed high minimum inhibitory concentration (MIC) values (≥ 4 µg/mL) to itraconazole by M38-A2 of CLSI were selected. At the hospital consultation, disseminated (cats 1-l0, 12) and localized (cat 11) skin lesions remained in the cats, even after treatment with fluconazole, ketoconazole (02/12), and itraconazole (ITZ, 09/12) performed before this study. High doses (25-100 mg/kg/day) of ITZ for up to 4 months (03/12, cats 2, 6, 12) or over 12 months (05/12, cats 1, 5, 7, 8, 11) did not provide a clinical cure, except for the association of ITZ plus potassium iodide (01/12, cat 12) for 3 months, which proved useful in infections with itraconazole-resistant S. brasiliensis. However, the combined issues of abandonment of therapy by owners for financial reasons, difficulties surrounding therapy administration (03/12, cats 6, 11, 12), and the inappropriate choice of medication (01/12, cat 6), together reflect the reality of this endemic region, which greatly compromises clinical healing. This study highlighted the occurrence of refractory cases by itraconazole-resistant S. brasiliensis in cats from Southern Brazil, as well as the abandonment of treatment and therapeutic errors. We warn of the need for antifungal susceptibility tests to adapt therapeutic protocols in feline sporotrichosis.
Assuntos
Antifúngicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Farmacorresistência Fúngica , Itraconazol/uso terapêutico , Sporothrix/efeitos dos fármacos , Esporotricose/veterinária , Animais , Brasil , Doenças do Gato/microbiologia , Gatos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Sporothrix/fisiologia , Esporotricose/tratamento farmacológico , Esporotricose/microbiologiaRESUMO
Chromoblastomycosis (CBM) is a chronic granulomatous fungal infection caused by melanised or brown-pigmented fungi. It can lead to chronic persistent infections and may cause incapacity for labour in some severe clinical forms. The optimal therapy for CBM is still uncertain. Here, we reported the case of a 66-year-old male who has had red plaque and recurrent keratinised protrusions on his right forearm for 20 years. He was treated orally with terbinafine, itraconazole and isotretinoin. He also received carbon dioxide(CO2 ) laser to eradicate the keratinised protrusions and promote the penetration of photosensitiser. After the CO2 laser, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) was adopted immediately to inhibiting the growth of fungi in subcutaneous tissue. The patient received an important improvement with a plaque and crust reduction after 4 months. For such recalcitrant case of chromoblastomycosis, the use of retinoid, CO2 laser combined with ALA-PDT may be a new adjuvant therapy. We further reviewed the cases of chromoblastomycosis treated with laser, photodynamic therapy or retinoic acid.
Assuntos
Antifúngicos/uso terapêutico , Cromoblastomicose/terapia , Fotoquimioterapia/métodos , Retinoides/uso terapêutico , Idoso , Ácido Aminolevulínico/uso terapêutico , Cromoblastomicose/diagnóstico por imagem , Cromoblastomicose/patologia , Humanos , Isotretinoína/uso terapêutico , Itraconazol/uso terapêutico , Lasers , Lasers de Gás/uso terapêutico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Terbinafina/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Trichosporiosis is an opportunistic infection that includes superficial infections, white piedra, hypersensitivity pneumonitis, and invasive trichosporonosis. The effect of antifungal agents against these infections is largely weakened by drug resistance and biofilms-related virulence. Photodynamic therapy (PDT) is a new therapeutic approach developed not only to combat cancerous lesions but also to treat infectious diseases such as fungal infections. However, there are few studies on the antimicrobial mechanism of 5-aminolevulinic acid PDT (ALA-PDT) in treating Trichosporon. In this work, we explored the possibility of combining ALA-PDT with an antifungal agent to enhance the therapeutic efficacy of Trichosporon asahii (T. asahii) in a clinical setting and in vitro. STUDY DESIGN/MATERIALS AND METHODS: The biofilms of T. asahii were constructed by a 96-well plate-based method in vitro. The planktonic and adherent T. asahii were exposed to different concentrations of photosensitizers and different light doses. After PDT treatment, counting colony-forming units and tetrazolium (XTT) reduction assay were used to estimate the antifungal efficacy. The minimal inhibitory concentration of itraconazole before and after PDT treatment was determined by the broth dilution method, and XTT viability assay was used to detect and evaluate the synergistic potential of ALA-PDT and itraconazole combinations in inhibiting biofilms. Scanning electron microscopy (SEM) was performed to assess the disruption of biofilms. RESULTS: Using combination therapy, we have successfully treated a patient who had a T. asahii skin infection. Further in vitro studies showed that the antifungal effect of ALA-PDT on planktonic and adherent T. asahii was dependent on the concentration of ALA and light dosages used. We also found that the sensitivity of both planktonic and biofilm cells to itraconazole were increased after ALA-PDT. Synergistic effect were observed for biofilms in ALA-PDT and itraconazole-combined treatment. The disruption of biofilms was confirmed by SEM, suggesting that ALA-PDT effectively damaged the biofilms and the destruction was further enhanced by ALA-PDT combination of antifungal agents. CONCLUSIONS: In conclusion, these data suggest that ALA-PDT could be an alternative strategy for controlling infections caused by Trichosporon. The combination therapy of ALA-PDT with itraconazole could result in increased elimination of planktonic cells and biofilms compared with single therapy. All these findings indicate that it could be a promising treatment against trichosporonosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
Assuntos
Fotoquimioterapia , Trichosporon , Tricosporonose , Basidiomycota , Biofilmes , Humanos , Itraconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Tricosporonose/tratamento farmacológicoRESUMO
BACKGROUND: Cutaneous sporotrichosis, a subcutaneous mycosis because of Sporothrix schenckii, is sporadic worldwide with local hyperendemic pockets. OBJECTIVES: To study clinico-epidemiological and therapeutic aspects of sporotrichosis in our clinic. METHODS: We retrospectively analyzed medical records of 152 (M:F 52:100) patients with cutaneous sporotrichosis managed during 2010-2019. RESULTS: All patients were involved in agricultural activities, and 63.2% were aged 21-60 years. Women outnumbered men by nearly two times. Fixed and lymphocutaneous sporotrichosis occurred in 54.6% and 43.4% patients, respectively. Only 2% of patients had multifocal sporotrichosis. Only 48% of patients imputed their disease to prior injuries. Extremities, upper in 53.9% and lower in 21% of patients, were mostly involved. Scrotum involvement in one patient was unusual. A mixed inflammatory infiltrate in 38.7%, chronic granuloma formation in 35%, and presence of spores in 48.9% biopsies was noted. S. schenckii grew on Sabouraud's dextrose agar in 40.2% of cases. Treatment with saturated solution of potassium iodide was curative in 76.8% patients, and lesions healed in 2-9 months (average 5.2 months). Metallic taste was experienced by 42.9% of patients. Itraconazole therapy was safe and effective in seven patients, and the response was better when combined with SSKI compared to either drug used alone. CONCLUSION: Cutaneous sporotrichosis mostly affects persons during active years of life. The injuries predisposing to infection are mostly forgotten. Both fixed and lymphocutaneous sporotrichosis involving extremities remain common forms. SSKI alone or in combination with itraconazole is safe and effective treatment. Itraconazole is preferable in patients having preexisting hypothyroidism or intolerance to SSKI.
Assuntos
Agricultura , Antifúngicos/uso terapêutico , Granuloma/microbiologia , Doenças Profissionais/tratamento farmacológico , Iodeto de Potássio/uso terapêutico , Esporotricose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Criança , Tratamento Farmacológico , Extremidades , Feminino , Humanos , Índia/epidemiologia , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Doenças Profissionais/patologia , Iodeto de Potássio/efeitos adversos , Estudos Retrospectivos , Esporos Fúngicos , Esporotricose/epidemiologia , Esporotricose/etiologia , Esporotricose/patologia , Ferimentos e Lesões/complicações , Adulto JovemAssuntos
Cromoblastomicose , Fonsecaea , Melanócitos/patologia , Antifúngicos/uso terapêutico , Cromoblastomicose/diagnóstico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/patologia , Diagnóstico Diferencial , Fonsecaea/classificação , Fonsecaea/isolamento & purificação , Mãos/microbiologia , Mãos/patologia , Humanos , Hipertermia Induzida , Inflamação , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/patologia , Patologia Molecular , Vitiligo/diagnóstico , Vitiligo/patologiaRESUMO
BACKGROUND: Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. PRINCIPAL FINDINGS: We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. CONCLUSIONS: These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Antifúngicos/uso terapêutico , Ascomicetos/efeitos dos fármacos , Ascomicetos/efeitos da radiação , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/radioterapia , Fotoquimioterapia/métodos , China , Cromoblastomicose/patologia , DNA Fúngico , Feminino , Humanos , Itraconazol/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pele/metabolismo , Terbinafina/uso terapêutico , Voriconazol/uso terapêuticoRESUMO
In vitro and clinical data were analysed to evaluate the susceptibility profile of itraconazole in light of the new cut-off points. The in vitro activity of itraconazole was compared with that of eight comparators against 119 Candida bloodstream isolates from 2015 to 2018. Minimum inhibitory concentrations (MICs) were measured by the colorimetric MICRONAUT-S assay. The content of wells without any color change was sub-cultured to measure killing efficacy. No major differences were found against Candida albicans. Itraconazole, posaconazole and amphotericin B were the most active agents against Candida parapsilosis. Of the 32 isolates of C. parapsilosis that were resistant to fluconazole, 96.9%, 78.1% and 93.8% were susceptible to itraconazole, voriconazole and posaconazole, respectively. The ratio of the minimum fungicidal concentration (MFC) to the MIC of itraconazole was lower than for the other azoles against C. parapsilosis and C. glabrata. Itraconazole achieved greater inhibition over-time of the growth of C. parapsilosis than fluconazole. Seventy-three critically ill patients who were unresponsive to antibiotics received intravenous empirical treatment with itraconazole (nâ¯=â¯28) or comparators (nâ¯=â¯45). Case-control matching was conducted for severity, comorbidities, risk factors for candidemia, administered antibiotics and days of antifungal treatment. Breakthrough candidemia was found in 3.6% of patients treated with itraconazole and in 32.1% of patients treated with comparators (P: 0.020); breakthrough candidemia by C. parapsilosis was found in 3.6% and 28.6% of patients, respectively. Results indicate that itraconazole retains a valuable susceptibility profile against Candida isolates, particularly C. parapsilosis. This superior profile may explain the clinical efficacy in the occurrence of breakthrough candidemia and warrants further clinical investigation.
Assuntos
Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidemia/tratamento farmacológico , Candidemia/microbiologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/classificação , Candida/isolamento & purificação , Estado Terminal , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
MIC values for amphotericin B and three azoles determined by the EUCAST reference technique and by gradient concentration strips were compared for 30 Mucorales isolates belonging to clinically important species. Essential agreement (EA) within ±2 dilution steps at 24 hours between the techniques was 83.3% for isavuconazole. EAs for itraconazole, amphotericin B, and posaconazole were 86.7%, 73.3%, and 56.7%, respectively. A good agreement was obtained between visual and spectrophotometric readings for EUCAST.
Assuntos
Antifúngicos/uso terapêutico , Mucorales/efeitos dos fármacos , Nitrilas/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Anfotericina B/uso terapêutico , Azóis/uso terapêutico , Humanos , Itraconazol/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
In this study, we described the antifungal activity of three Brazilian propolis extracts: brown, green and from jataí bees against Sporothrix brasiliensis. The extracts were obtained from ethanolic extraction and their chemical composition was determined by high-performance liquid chromatography coupled to mass spectrometry. The cellular toxicity was measured in MDBK (Madin-Darby Bovine Kidney) cells and quantified by the MTT assay (3- (4,5 dimethylthiazol-2yl -2,5-diphenyl-2H bromine tetrazolato). For antifungal activity, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined by broth microdilution. The results showed that cell toxicity was not observed at lower concentrations (0.097 to 0.39μg/ml) for all extracts in comparison to cell control. Among the chemical compounds identified, caffeic acid, p-coumaric acid, chlorogenic acid, ferulic acid and rutin were quantified. In antifungal activity, green and jataí did not exhibit activity against the isolates (MIC and MFC greater than 0.78mg/ml). However, all isolates of S. brasiliensis were sensitive to brown propolis (MIC of 0.09 to 0.78mg/ml), including the standard strain (P<0.001). Among the Brazilian propolis studied, the brown propolis showed activity against the S. brasiliensis isolates and more studies should be undertaken in order to evaluate its promising use in the treatment of sporotrichosis.(AU)
Neste estudo, descreveu-se a atividade antifúngica de três extratos de própolis brasileiras: marrom, verde e de abelhas jataí (Tetragonisca angustula), contra Sporothrix brasiliensis. Os extratos foram obtidos de extração etanólica, e a sua composição química foi determinada por cromatografia líquida de alta eficiência, acoplada à espectrometria de massa. A toxicidade celular foi medida em células MDBK (Madin-Darby Bovine Kidney), avaliada por observação microscópica e quantificada pelo ensaio MTT (3- (4,5-dimetiltiazol-2-ilo -2,5-difenil-2H bromo tetrazolato). Para a atividade antifúngica, determinou-se a concentração inibitória mínima (CIM) e a concentração fungicida mínima (CFM) por meio de microdiluição em caldo. Os resultados mostraram que a toxicidade celular não foi observada em concentrações menores (0,097 a 0,39μg/ml). Entre os compostos químicos identificados, foram quantificados o ácido cafeico, ácido p-cumárico, ácido clorogênico, ácido ferúlico e a rutina. Na atividade antifúngica, as própolis verde e jataí não apresentaram atividade contra os isolados (CIM e CFM maior que 0,78mg/ml), porém todos os isolados de S. brasiliensis foram sensíveis à própolis marrom (CIM de 0,09 a 0,78mg/ml), incluindo a cepa padrão (P<0,001). Entre as própolis brasileiras estudadas, a marrom mostrou atividade contra S. brasiliensis, e mais estudos devem ser realizados para avaliar seu uso promissor no tratamento da esporotricose.(AU)