RESUMEN
Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.
Asunto(s)
Anfotericina B , Antifúngicos , Melanogénesis , Inhibidores de la Bomba de Protones , Sporothrix , Esporotricosis , Humanos , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Itraconazol/farmacología , Melaninas/biosíntesis , Melaninas/metabolismo , Melanogénesis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Sporothrix/efectos de los fármacos , Sporothrix/metabolismo , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Terbinafina/farmacologíaRESUMEN
BACKGROUND: Terbinafine has been successfully used in the treatment of human sporotrichosis; however, its effectiveness in the treatment of feline sporotrichosis is unknown. Therefore, this study aimed to describe the use of terbinafine in the treatment of feline sporotrichosis. METHODS: A cohort study was conducted in cats with sporotrichosis to assess the effectiveness and safety of terbinafine (30â60 mg/kg/day). Clinical examination and analysis of laboratory parameters were performed monthly until clinical signs resolved or terbinafine treatment was discontinued. RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug. Of the remaining 30 cats, 10 achieved clinical cure, with a median treatment time of 18.5 weeks. Treatment failed in 18 cases, and two cats died. Twenty-two cats had adverse reactions to terbinafine treatment, and 10 cats showed elevation of serum transaminases. LIMITATION: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes. CONCLUSION: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.
Asunto(s)
Antifúngicos , Enfermedades de los Gatos , Esporotricosis , Terbinafina , Gatos , Animales , Terbinafina/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Esporotricosis/tratamiento farmacológico , Esporotricosis/veterinaria , Antifúngicos/uso terapéutico , Antifúngicos/efectos adversos , Resultado del Tratamiento , Masculino , Femenino , Estudios de CohortesRESUMEN
Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5-5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n = 12) and 1.0 µg/mL in those treated with ITZ + KI (n = 4). The clinical cure rate was 56.3% (n = 9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions, and hyporexia was the most frequent (n = 8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ + KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.
Itraconazole is the most common therapy for feline sporotrichosis, and combination therapy with potassium iodide is used in nonresponsive cases. Our study showed that all cats achieved a therapeutic plasma concentration of itraconazole, with higher levels in cats treated with the combination therapy.
Asunto(s)
Antifúngicos , Enfermedades de los Gatos , Itraconazol , Yoduro de Potasio , Esporotricosis , Animales , Gatos , Esporotricosis/tratamiento farmacológico , Esporotricosis/veterinaria , Esporotricosis/sangre , Itraconazol/sangre , Itraconazol/farmacocinética , Itraconazol/administración & dosificación , Itraconazol/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/microbiología , Antifúngicos/farmacocinética , Antifúngicos/sangre , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Masculino , Yoduro de Potasio/uso terapéutico , Yoduro de Potasio/administración & dosificación , Yoduro de Potasio/farmacocinética , Femenino , Resultado del Tratamiento , Quimioterapia Combinada , Administración Oral , Plasma/químicaAsunto(s)
Enfermedades de los Gatos , Sporothrix , Esporotricosis , Esporotricosis/epidemiología , Esporotricosis/microbiología , Esporotricosis/veterinaria , Esporotricosis/tratamiento farmacológico , Brasil/epidemiología , Gatos , Humanos , Animales , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/epidemiología , Sporothrix/aislamiento & purificación , Zoonosis/transmisión , Zoonosis/microbiología , Zoonosis/epidemiologíaRESUMEN
Sporotrichosis, a mycosis resulting from cutaneous or subcutaneous infection with the dimorphic fungus Sporothrix, has been reported in China, particularly in the northeast region. In this review, we conducted a thorough examination of the recent advancements in sporotrichosis in China, encompassing aspects such as etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment strategies. Within the Chinese context, fixed cutaneous sporotrichosis represents the prevailing clinical manifestation. Fungal culture stands as the gold standard for diagnosing sporotrichosis, while polymerase chain reaction techniques can enhance both the specificity and sensitivity of diagnosis. Besides conventional systemic antifungal agents, alternative modalities such as Chinese herbal medicines, photodynamic therapy and laser therapy show potential efficacy against sporotrichosis.
Sporotrichosis is a fungal infection on the skin. It is caused by a group of fungi called Sporothrix. Common symptoms are lesions on the skin, inflammatory papules, nodules and ulcers. These fungi live in the natural environment and cause infection by entering the body through a wound in the skin. China has a high prevalence of sporotrichosis, with northeast China the most seriously affected region. This review looks at the state of sporotrichosis in China.
Asunto(s)
Antifúngicos , Sporothrix , Esporotricosis , Esporotricosis/epidemiología , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Esporotricosis/diagnóstico , China/epidemiología , Humanos , Sporothrix/aislamiento & purificación , Sporothrix/genética , Sporothrix/efectos de los fármacos , Antifúngicos/uso terapéutico , Reacción en Cadena de la Polimerasa , FotoquimioterapiaRESUMEN
Sporotrichosis is a globally distributed subcutaneous mycosis caused by dimorphic Sporothrix species commonly found in soil, mosses, and decaying plant matter. The lymphocutaneous manifestation, historically associated with occupational activities and sapronotic transmission, has recently been observed to also occur through animal contact, particularly notable in Brazil. We describe a rare case of lymphocutaneous sporotrichosis with simultaneous pulmonary complications resulting from the scratching of a southern three-banded armadillo, Tolypeutes matacus, primarily inhabiting the arid forests of South America's central region. Speciation using multiplex quantitative polymerase chain reaction (qPCR) established the etiological agent as S. schenckii s. str., while amplified fragment length polymorphism (AFLP) analysis unveiled a novel genotype circulating in the Midwest of Brazil. The patient received treatment with itraconazole (200 mg/day) for two months, leading to substantial clinical improvement of cutaneous and pulmonary symptoms. This case highlights the critical role of animal-mediated transmission in sporotrichosis epidemiology, particularly within regions with diverse armadillo species. The unusual epidemiology and genetic characteristics of this case emphasize the need for enhanced awareness and diagnostic vigilance in atypical sporotrichosis presentations.
Asunto(s)
Antifúngicos , Armadillos , Itraconazol , Sporothrix , Esporotricosis , Animales , Humanos , Masculino , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Antifúngicos/uso terapéutico , Armadillos/microbiología , Brasil , Genotipo , Itraconazol/uso terapéutico , Reacción en Cadena de la Polimerasa Multiplex , Sporothrix/genética , Sporothrix/aislamiento & purificación , Sporothrix/clasificación , Esporotricosis/microbiología , Esporotricosis/diagnóstico , Esporotricosis/tratamiento farmacológico , Esporotricosis/transmisión , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
Sporotrichosis is recognized as the predominant subcutaneous mycosis in South America, attributed to pathogenic species within the Sporothrix genus. Notably, in Brazil, Sporothrix brasiliensis emerges as the principal species, exhibiting significant sapronotic, zoonotic and enzootic epidemic potential. Consequently, the discovery of novel therapeutic agents for the treatment of sporotrichosis is imperative. The present study is dedicated to the repositioning of pharmaceuticals for sporotrichosis therapy. To achieve this goal, we designed a pipeline with the following steps: (a) compilation and preparation of Sporothrix genome data; (b) identification of orthologous proteins among the species; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Sporothrix essential targets using validated genes from Saccharomyces cerevisiae; (e) molecular modeling studies; and (f) experimental validation of selected candidates. Based on this approach, we were able to prioritize eight drugs for in vitro experimental validation. Among the evaluated compounds, everolimus and bifonazole demonstrated minimum inhibitory concentration (MIC) values of 0.5 µg/mL and 4.0 µg/mL, respectively. Subsequently, molecular docking studies suggest that bifonazole and everolimus may target specific proteins within S. brasiliensis- namely, sterol 14-α-demethylase and serine/threonine-protein kinase TOR, respectively. These findings shed light on the potential binding affinities and binding modes of bifonazole and everolimus with their probable targets, providing a preliminary understanding of the antifungal mechanism of action of these compounds. In conclusion, our research advances the understanding of the therapeutic potential of bifonazole and everolimus, supporting their further investigation as antifungal agents for sporotrichosis in prospective hit-to-lead and preclinical investigations.
Asunto(s)
Antifúngicos , Reposicionamiento de Medicamentos , Genoma Fúngico , Pruebas de Sensibilidad Microbiana , Sporothrix , Esporotricosis , Sporothrix/efectos de los fármacos , Sporothrix/genética , Antifúngicos/farmacología , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Brasil , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Simulación del Acoplamiento Molecular , Genómica , Humanos , Evaluación Preclínica de Medicamentos , Descubrimiento de Drogas , Biología ComputacionalRESUMEN
A 26-year-old woman presented an eyelid lesion, after being scratched by a cat that had a similar skin lesion. It evolved into a cervical lymph node enlargement. With a hypothesis of Parinaud´s oculoglandular syndrome (POS) due to cat scratch disease (CSD), doxycycline was prescribed. After two weeks of treatment without improvement, a biopsy and blood sample were obtained. Itraconazole was prescribed and the skin lesion improved, but not the lymph node enlargement. A Sporothrix schenckii complex was isolated from the skin sample. Also, a specie-specific polymerase chain reaction detected Bartonella henselae DNA in her blood sample. Azithromycin was included to treat the bacterial infection, whereupon the lymph node also receded successfully. Sporotrichosis and CSD are zoonoses that can be transmitted to humans by traumatic inoculation due to scratches or bites from cats. Both can evolve with POS. Patients who present skin lesions and/or POS after being wounded by a cat should be investigated for both diseases.
Asunto(s)
Antibacterianos , Bartonella henselae , Enfermedad por Rasguño de Gato , Coinfección , Sporothrix , Esporotricosis , Femenino , Bartonella henselae/aislamiento & purificación , Bartonella henselae/genética , Humanos , Adulto , Sporothrix/aislamiento & purificación , Sporothrix/genética , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Esporotricosis/diagnóstico , Coinfección/microbiología , Animales , Gatos , Antibacterianos/uso terapéutico , Enfermedad por Rasguño de Gato/microbiología , Enfermedad por Rasguño de Gato/tratamiento farmacológico , Enfermedad por Rasguño de Gato/complicaciones , Enfermedad por Rasguño de Gato/diagnóstico , Azitromicina/uso terapéutico , Itraconazol/uso terapéutico , Doxiciclina/uso terapéutico , Piel/microbiología , Piel/patologíaRESUMEN
Sporotrichosis is a widespread fungal infection that affects skin and subcutaneous tissues in humans and animals. In cats, it is displayed as nodules, ulcers and lesions on the nasal and respiratory mucosa. Antifungal treatment of cats is crucial but many cases are difficult, thus resulting in discontinue of the treatment, with disastrous consequences for the animal, encouraging contamination of the environment, other animals and people. The effects of responsible ownership education and health education for owners of cats with feline sporotrichosis as well as the interval between veterinary consultations on treatment outcomes for three groups of owners and their pet cats were evaluated in this study. The responsible ownership education and health education strategies consisted in videos in easy and accessible language for people with any level of education and were presented during consultations for two of the three groups included. The time between appointments was two weeks for two of the groups, and four weeks for one of the groups. The median of treatment time for the group without educational activities was 138 days, while for the other two groups it was 77.5 days and 86 days. It was found a significative reduction in the treatment time in the groups exposed to Responsible ownership education videos. There was no contamination of those responsible for home treatment, and the interval between monthly appointments did not impact on cure or death rates compared to the interval between fortnightly appointments. All these results can be applied to feline sporotrichoses treatment protocols increasing the owners treatment adherence and reducing either, the treatment discontinuation and the treatment costs and helps to control zoonotic sporotrichosis. The importance of attractive and comprehensible educational strategies as part of the feline sporotrichosis treatment protocol for the promotion of one health was highlighted.
Asunto(s)
Enfermedades de los Gatos , Educación en Salud , Propiedad , Esporotricosis , Animales , Gatos , Enfermedades de los Gatos/terapia , Enfermedades de los Gatos/prevención & control , Enfermedades de los Gatos/microbiología , Esporotricosis/veterinaria , Esporotricosis/tratamiento farmacológico , Esporotricosis/prevención & control , Esporotricosis/terapia , Humanos , Femenino , Masculino , Antifúngicos/uso terapéuticoRESUMEN
A esporotricose é uma doenças causada por fungos do gênero Sporothrix, normalmente em regiões tropicais ou subtropicais. O Sporothrix brasiliensis é o agente etiológico mais descrito nos animais. Apesar de não ser uma doença de notificação compulsória nacional, desde o ano de 2023, tem-se orientado a notificação dos casos suspeitos e/ou confirmados de esporotricose humana e animal no estado de Goiás, através do Sistema de informação de Agravos de Notificação (Sinan) e do REDCap, respectivamente
Sporotrichosis is a disease caused by fungi of the genus Sporothrix, normally in tropical or subtropical regions. Sporothrix brasiliensis is the most described etiological agent in animals. Despite not being a nationally notifiable disease, since 2023, the notification of suspected and/or confirmed cases of human and animal sporotrichosis in the state of Goiás has been advised, through the Notifiable Diseases Information System ( Sinan) and REDCap, respectively
Asunto(s)
Humanos , Animales , Gatos , Perros , Esporotricosis/epidemiología , Esporotricosis/diagnóstico , Esporotricosis/prevención & control , Esporotricosis/tratamiento farmacológicoRESUMEN
BACKGROUND: Facial cutaneous sporotrichosis presents with diverse clinical manifestations, often leading to misdiagnosis. OBJECTIVE: This study aims to present the clinical characteristics of five misdiagnosed cases of facial cutaneous sporotrichosis, aiming to enhance understanding of this disease and prevent misdiagnosis and mistreatment. METHODS: Clinical data, histopathology, and fungal culture results of these five cases were comprehensively analyzed. RESULTS: Among these five patients, three presented with lymphocutaneous sporotrichosis, while two had the fixed cutaneous type. Due to misdiagnosis, initial treatments were ineffective for all patients. Upon histopathological examination and fungal culture confirming sporotrichosis, treatment with itraconazole for 3 months led to complete resolution of lesions. While one patient experienced a relapse due to noncompliance with the prescribed medication. CONCLUSION: Facial sporotrichosis, with its diverse clinical manifestations and obscure trauma history, is prone to misdiagnosis. Timely and thorough examinations are crucial for precise diagnosis and management. Itraconazole treatment demonstrated notable efficacy, and patient compliance is also essential for favorable outcomes.
Asunto(s)
Antifúngicos , Errores Diagnósticos , Dermatosis Facial , Itraconazol , Esporotricosis , Humanos , Esporotricosis/diagnóstico , Esporotricosis/tratamiento farmacológico , Femenino , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Antifúngicos/uso terapéutico , Adulto , Masculino , Dermatosis Facial/diagnóstico , Dermatosis Facial/tratamiento farmacológico , Dermatosis Facial/microbiología , Persona de Mediana EdadRESUMEN
Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
Asunto(s)
Antifúngicos , Enfermedades de los Gatos , Quimioterapia Combinada , Itraconazol , Sporothrix , Esporotricosis , Gatos , Animales , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Itraconazol/farmacología , Esporotricosis/tratamiento farmacológico , Esporotricosis/veterinaria , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/administración & dosificación , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/microbiología , Sporothrix/efectos de los fármacos , Hidrazonas/uso terapéutico , Hidrazonas/farmacología , Femenino , Masculino , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Resultado del TratamientoRESUMEN
The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.
Asunto(s)
Antihelmínticos , Antifúngicos , Pruebas de Sensibilidad Microbiana , Niclosamida , Sporothrix , Sporothrix/efectos de los fármacos , Sporothrix/genética , Sporothrix/clasificación , Niclosamida/farmacología , Antifúngicos/farmacología , Antihelmínticos/farmacología , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Genotipo , Humanos , Farmacorresistencia Fúngica , Sinergismo FarmacológicoRESUMEN
Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.
Asunto(s)
Sporothrix , Esporotricosis , Humanos , Antifúngicos/farmacología , Azoles/farmacología , Brasil , Filogenia , Itraconazol/farmacología , Esporotricosis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica/genéticaRESUMEN
BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.
Asunto(s)
Antifúngicos , Sporothrix , Esporotricosis , Esporotricosis/tratamiento farmacológico , Esporotricosis/diagnóstico , Humanos , Sporothrix/aislamiento & purificación , Antifúngicos/uso terapéutico , Gatos , Masculino , Adulto , Femenino , Animales , Brasil/epidemiología , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Infecciones Fúngicas del Sistema Nervioso Central/mortalidad , Estados Unidos/epidemiologíaRESUMEN
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.
Asunto(s)
Infecciones por VIH , Hipertermia Inducida , Sporothrix , Esporotricosis , Adulto , Humanos , Masculino , Esporotricosis/tratamiento farmacológico , Esporotricosis/patología , Itraconazol/uso terapéutico , Itraconazol/farmacología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológicoRESUMEN
INTRODUCTION: Sporotrichosis, a zoonosis caused by animal, mainly cat, scratches or bites, is caused by fungi belonging to the Sporothrix complex. Treatment usually consists in antifungal administration, although treatment failure and hepatotoxicity reports have been noted. Alternative sporotrichosis treatment methods, such as antimicrobial photodynamic therapy (aPDT), may, therefore, be indicated. CASE REPORT: In this context, this study followed a 56-year-old male renal transplanted patient displaying disseminated sporotrichosis, presenting erythematous skin lesions with ulcerated backgrounds and hardened consistency on the nose, oral and scalp. The lesions were present for about 2 months and the patient coexisted with cats. Intravenous amphotericin B administration was initiated, and immunosuppression was suspended. Seven aPDT sessions were also performed in 48 h intervals on the oral lesions, employing 0.01% methylene blue gel as the photosensitizing agent. After the 4th aPDT session, the patient was discharged, amphotericin B administration was suspended, and the treatment was continued with itraconazole, without immunosuppression. Red laser was applied to the oral lesions after the 7th aPDT session. Significant lesion improvement was observed after the final aPDT session and complete palate lesion repair was noted after two red laser sessions. CONCLUSION: These findings indicate that aPDT is a valuable strategy as an adjunct sporotrichosis treatment.