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1.
Case Rep Transplant ; 2024: 8892177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372424

RESUMO

Cladophialophora bantiana is a dematiaceous fungi and the most common cause of cerebral phaeohyphomycosis. Here, we report a rare case of cerebral ventriculitis with development of a cerebral abscess due to C. bantiana diagnosed by cell-free DNA next-generation sequencing. Noninvasive diagnostics led to earlier disease identification and initiation of antifungal therapy, which has the potential to reduce mortality in this highly fatal disease.

2.
Mycoses ; 67(9): e13796, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39278821

RESUMO

BACKGROUND: Chromoblastomycosis (CBM) is a chronic infection of skin and subcutaneous tissue. CBM cases have been reported in local literature from Pakistan with heterogenous demographic, diagnostic and therapeutic information. The objective of this study is to share the experience of CBM from a large tertiary care hospital laboratory in Pakistan. METHOD: This was a retrospective observational study. Histopathology and microbiology data of suspected CBM between 2016 and 2022 was retrieved. Patients' demographics, site of involvement, histopathological findings and positive microbiology cultures were assessed. Literature search on Google Scholar, PubMed and PakMediNet was done between 1990 and 2023 with multiple terms. RESULT: A total of 16 CBM cases were identified; 14 were histopathology positive and two were both histopathology and culture positive. The median age was 21 years, and 11 patients were male. The predominant site was lower extremities followed by the face. Severe acanthosis, hyperkeratosis and granuloma with sclerotic bodies were observed in all histopathology slides. Alternaria spp. and Phialophora spp. were isolated from two culture-positive cases. A total of nine cases of CBM were reported from Pakistan in PubMed non-indexed journal. CONCLUSION: CBM is not a commonly thought of disease when evaluating skin lesions in Pakistan. A high index of suspicion when assessing patients who may have a history of trauma, exposure to soil and suggestive lesions is reasonable. An integrated approach between clinicians, histopathologist and microbiologist is required to do early identification and therapeutic interventions.


Assuntos
Cromoblastomicose , Humanos , Cromoblastomicose/microbiologia , Cromoblastomicose/diagnóstico , Cromoblastomicose/patologia , Cromoblastomicose/epidemiologia , Paquistão/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Adulto , Adulto Jovem , Adolescente , Centros de Atenção Terciária/estatística & dados numéricos , Pele/microbiologia , Pele/patologia , Pessoa de Meia-Idade , Criança , Antifúngicos/uso terapêutico
3.
Cureus ; 16(8): e67718, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39318939

RESUMO

Background Phaeohyphomycosis, a fungal infection caused by dematiaceous fungi, presents a significant health challenge affecting both immunocompromised and immunocompetent individuals. Despite its clinical importance, phaeohyphomycosis remains underrepresented in epidemiological studies, leading to gaps in our understanding of its prevalence, clinical manifestations, and associated risk factors. This retrospective study conducted in South India aims to address these gaps by examining the incidence, diverse clinical presentations, and other relevant epidemiological aspects of phaeohyphomycosis in patients referred for pathological examination. Objective To investigate the epidemiological trends, clinicopathological characteristics, and microbiological spectrum of phaeohyphomycosis in patients at a tertiary care center in South India over 10 years. Materials and methods This comprehensive study was conducted at Employees State Insurance Corporation Medical College & Post Graduate Institute of Medical Sciences and Research (ESIC Medical College and PGIMSR), Chennai, embodying a retrospective observational approach. Over a decade, researchers meticulously reviewed cases diagnosed with phaeohyphomycosis. This involved an in-depth analysis of patients' medical records to gather detailed information on presenting symptoms, history of thorn pricks, diabetic status, and other pertinent epidemiological data. Additionally, culture samples were selectively obtained from patients exhibiting abscesses or cystic swellings, followed by a thorough assessment of the culture reports. Results In the ten-year study period, a total of 46 cases were identified. Most lesions were solid or cystic and located on extremities, predominantly affecting the digits. Eight cases (17%) had a history of thorn prick injuries, and six cases (13%) were associated with diabetes mellitus. Microscopic examination revealed necrosis, granulomas, varying degrees of inflammatory infiltrates, giant cells, and pigmented fungal hyphae. In some cases, biopsies revealed pseudoepitheliomatous hyperplasia. Among the 19 cases where culture was performed, Alternaria was the most commonly isolated pathogen (42%). Conclusion The study brings to light the diagnostic challenges inherent in phaeohyphomycosis cases, which often eluded clinical diagnosis and were only conclusively identified via pathological examinations. While this research was primarily focused on outpatients presenting with minor symptoms, it underscores the potential for more severe clinical presentations in immunocompromised patients. Our findings emphasize the need for increased clinical awareness and the pivotal role of histopathological examination in accurately diagnosing phaeohyphomycosis, particularly in cases with extremity lesions. This study contributes significantly to the understanding of phaeohyphomycosis and advocates for ongoing research to better understand its epidemiology and clinical diversity.

4.
Microbiol Spectr ; 12(8): e0078124, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38920376

RESUMO

Primary cerebral phaeohyphomycosis is a life-threatening disease caused by neurotropic dematiaceous fungi. At present, there are no consensus guidelines regarding optimal antifungal therapy in such cases. Generally, a combination of antifungal agents is recommended for treatment. However, the activities of antifungal combinations against these fungi have not been investigated. In this study, we evaluated the in vitro activities of 13 double and five triple antifungal combinations against clinical isolates of Cladophialophora bantiana (n = 7), Fonsecaea monophora (n = 2), and Cladosporium cladosporioides (n = 1), using a simplified checkerboard procedure. The minimum inhibitory concentrations (MICs) of nine antifungal drugs were determined by the broth microdilution method, and the interaction between antifungal agents in each combination was assessed by the fractional inhibitory concentration index. Excellent activity was observed for posaconazole and itraconazole. Flucytosine had potent activity against C. bantiana but was ineffective against F. monophora, and C. cladosporioides. The echinocandins demonstrated high MICs for all the isolates. Synergistic interactions were observed for all the double combinations, except when itraconazole was combined with either amphotericin B or flucytosine. The combination of amphotericin B with caspofungin showed synergistic interactions against 40% of the isolates. Antagonism was observed with isavuconazole-flucytosine combination against two C. bantiana isolates. The triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole were synergistic against one isolate of F. monophora. For C. cladosporioides, synergy was observed for the triple combination of amphotericin B with caspofungin and flucytosine. Our results indicate that combination of caspofungin with amphotericin B or a triazole, with or without 5-flucytosine has great potential against neurotropic dematiaceous fungi.IMPORTANCEThis research uses a modified version of the checkerboard assay to standardize the in vitro testing of double and triple combinations of antifungal agents against neurotropic dematiaceous fungi. Antifungal combination therapy is associated with improved outcomes in cerebral phaeohyphomycosis. In this study, we demonstrate that posaconazole is the single most active antifungal drug against this group of fungi. The double combination of amphotericin B with caspofungin or a trizole, and the triple combinations of caspofungin and flucytosine with amphotericin B or posaconazole might hold promise in the treatment of cerebral phaeohyphomycosis. Our findings will guide in developing optimal therapeutic strategies for these refractory infections.


Assuntos
Antifúngicos , Feoifomicose Cerebral , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Humanos , Feoifomicose Cerebral/tratamento farmacológico , Feoifomicose Cerebral/microbiologia , Ascomicetos/efeitos dos fármacos , Cladosporium/efeitos dos fármacos , Triazóis/farmacologia , Quimioterapia Combinada , Flucitosina/farmacologia , Itraconazol/farmacologia , Equinocandinas/farmacologia
5.
Indian J Med Microbiol ; 49: 100605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38734140

RESUMO

Cerebral phaeohyphomycosis (CP) stands as an exceedingly uncommon yet severe type of fungal infection affecting the central nervous system, attributable to dematiaceous fungi. Despite the patient's immune status, CP is associated with grave prognosis. In the present study, authors describe the first case of left thalamic fungal abscess due to Rhinocladiella mackenziei in an immunocompetent 39-year-old male patient in Jaipur, Rajasthan. Early diagnosis by direct microscopy of aspirated pus and extensive management with surgical excision and prolonged antifungal coverage showed favourable outcome. The present case is one of the few cases documented globally who has survived.


Assuntos
Antifúngicos , Abscesso Encefálico , Humanos , Masculino , Adulto , Abscesso Encefálico/microbiologia , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/tratamento farmacológico , Antifúngicos/uso terapêutico , Feoifomicose Cerebral/diagnóstico , Feoifomicose Cerebral/microbiologia , Índia , Tálamo/patologia , Tálamo/microbiologia , Tálamo/diagnóstico por imagem , Resultado do Tratamento
6.
Cureus ; 16(2): e53863, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465023

RESUMO

Chromoblastomycosis is a rare fungal infection acquired by traumatic inoculation of pigmented fungi from an environmental source. The polymorphic presentation of chromoblastomycosis may mimic other dermatologic conditions, leading to delays in diagnosis. Thus, histopathology is critical in identifying the presence of fungi and confirming the diagnosis. We present a case of chromoblastomycosis caused by the organism Fonsecaea monophora mimicking a lesion of lichen planus to highlight the importance of histopathology in the diagnosis of this condition.

7.
Front Cell Infect Microbiol ; 14: 1296151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304196

RESUMO

Introduction: Azole resistance has been increasingly reported and become an issue for clinical managements of invasive mycoses. New strategy with combination therapy arises as a valuable and promising alternative option. The aim of the present study is to investigate the in vitro combinational effect of proton pump inhibitors (PPIs) and azoles against pathogenic fungi. Methods: In vitro interactions of PPIs including omeprazole (OME), lansoprazole (LAN), pantoprazole (PAN), and rabeprazole (RAB), and commonly used azoles including itraconazole (ITC), posaconazole (POS), voriconazole (VRC) and fluconazole (FLC), were investigated via broth microdilution chequerboard procedure adapted from the CLSI M27-A3 and M38-A2. A total of 67 clinically isolated strains, namely 27 strains of Aspergillus spp., 16 strains of Candida spp., and 24 strains of dematiaceous fungi, were studied. C. parapsilosis (ATCC 22019) and A. flavus (ATCC 204304) was included to ensure quality control. Results: PPIs individually did not exert any significant antifungal activity. The combination of OME with ITC, POS, or VRC showed synergism against 77.6%, 86.6%, and 4% strains of tested pathogenic fungi, respectively, while synergism of OME/FLC was observed in 50% strains of Candida spp. Synergism between PAN and ITC, POS, or VRC was observed against 47.8%, 77.6% and 1.5% strains of tested fungi, respectively, while synergism of PNA/FLC was observed in 50% strains of Candida spp. Synergism of LAN with ITC, POS, or VRC was observed against 86.6%, 86.6%, and 3% of tested strains, respectively, while synergism of LAN/FLC was observed in 31.3% strains of Candida spp. Synergy of the combination of RAB with ITC, POS, or VRC was observed against 25.4%, 64.2%, and 4.5% of tested strains, respectively, while synergism of RAB/FLC was observed in 12.5% of Candida spp.. Among PPIs, synergism was least observed between RAB and triazoles, while among triazoles, synergism was least observed between VRC and PPIs. Among species, synergy was much more frequently observed in Aspergillus spp. and dematiaceous fungi as compared to Candida spp. Antagonism between PPIs with ITC or VRC was occasionally observed in Aspergillus spp. and dematiaceous fungi. It is notable that PPIs combined with azoles showed synergy against azole resistant A. fumigatus, and resulted in category change of susceptibility of ITC and POS against Candida spp. Discussion: The results suggested that PPIs combined with azoles has the potential to enhance the susceptibilities of azoles against multiple pathogenic fungi and could be a promising strategy to overcome azole resistance issues. However, further investigations are warranted to study the combinational efficacy in more isolates and more species, to investigate the underlying mechanism of interaction and to evaluate the potential for concomitant use of these agents in human.


Assuntos
Azóis , Inibidores da Bomba de Prótons , Humanos , Azóis/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Fungos , Antifúngicos/farmacologia , Triazóis/farmacologia , Voriconazol/farmacologia , Fluconazol/farmacologia , Candida , Aspergillus , Candida parapsilosis , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica
8.
Cureus ; 15(10): e46850, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37954775

RESUMO

We report on a case study involving a 58-year-old male with a pigmented corneal ulcer. The patient presented with a two-month history of an unresolved corneal ulcer in the oculus sinister (OS), accompanied by increasing ocular discomfort. His best corrected visual acuity (BCVA) was 20/20 oculus dexter and hand motion OS. Examination of OS revealed mild conjunctival injection, diffuse corneal edema, and the presence of a central pigmented lesion. Microbiological analysis via culture identified the causative agent as Ochroconis fungi, belonging to the dematiaceous species. Subsequently, the patient's condition was managed through a comprehensive regimen that included multiple topical antifungal agents, a topical antibiotic, and povidone-iodine drops. After two months of treatment, the patient exhibited improvement in his condition. His BCVA improved to counting fingers at a distance of two feet OS.

9.
J Dermatol ; 50(10): 1313-1320, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37381719

RESUMO

Exophiala species cause chromoblastomycosis, mycetoma, and phaeohyphomycosis, which are occasionally fatally in immunocompromised patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides rapid and accurate examination of isolated bacteria and some fungal isolates, but the preparation method for filamentous fungi is complicated. In this study, 31 clinical isolates of Exophiala spp. in Japan were identified by MALDI-TOF MS with a library enriched by adding data. To simplify the sample preparation method, two modified methods were compared with the standard method for filamentous fungi. The agar cultivation sample preparation method reduced the time required for liquid culture and was considered suitable for clinical use. In 30 of 31 clinical isolates of Exophiala spp., the species identified by MALDI-TOF MS with the highest score matched the species identified by sequencing the internal transcribed spacer region. Exophiala dermatitidis, E. lecanii-corni, and E. oligosperma were identified above the genus level, while E. jeanselmei and E. xenobiotica were often not identified at the species level. The identification scores tended to be lower for less-registered strains in the in-house library. It is suggested that library enrichment and the modified preparation method may facilitate early diagnosis of rare fungal infections by Exophiala spp. in clinical laboratories using MALDI-TOF MS.


Assuntos
Exophiala , Micoses , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Japão , Fungos
10.
Braz J Microbiol ; 54(3): 1899-1914, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37389796

RESUMO

The myrtle rust (MR), caused by Austropuccinia psidii, is a worldwide threat to the cultivated and wild Myrtaceae. Originally from the neotropics, it has spread to North America, Africa, and Asia and has reached geographically isolated areas in the Pacific and Australasia. It is attacking native species in those new ranges and is still spreading and causing great concern for the damage caused to endemic Myrtaceae, and to the environment. Classical biological control is regarded as the most sustainable management option for mitigating such biological invasions. However, there are no examples of introductions of host-specific co-evolved natural enemies of plant pathogens, from their native range, as a management strategy for plant pathogens. In order to explore this neglected approach, a survey of potential fungal natural enemies of A. psidii was initiated recently in the state of Minas Gerais (Brazil). Several purported mycoparasites have been collected from A. Psidii pustules formed on myrtaceous hosts. This included some isolates of dematiaceous fungi recognized as having a Cladosporium-like morphology. Here we present the results of the investigation aimed at elucidating their identity through a polyphasic taxonomic approach. Besides morphological and cultural features, molecular analyses using sequences of translation elongation factor 1-α (EF1) and actin (ACT) were performed. The combination of data generated is presented herein and placed all Cladosporium-like isolates in six species of Cladosporium, namely, Cladosporium angulosum, C. anthropophilum, C. bambusicola, C. benschii, C. guizhouense, and C. macadamiae. None of these have ever been recorded in association with A. psidii. Now, with the identification of these isolates at hand, an evaluation of biocontrol potential of these fungi will be initiated. In contrast with the ready finding of fungicolous (possibly mycoparasitic) fungi on MR in this study, no evidence of those was recorded from Australasia until now.


Assuntos
Basidiomycota , Myrtus , Brasil , Cladosporium/genética , Basidiomycota/genética
11.
Molecules ; 28(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298832

RESUMO

C. brachyspora, a widespread dematiaceous fungus, was evaluated in this study to optimize the production of exopolysaccharides (CB-EPS). Optimization was performed using response surface methodology, and the best production yielded 75.05% of total sugar at pH 7.4, with 0.1% urea, after 197 h. The obtained CB-EPS showed typical signals of polysaccharides, which was confirmed by FT-IR and NMR. The HPSEC analysis indicated a polydisperse polymer, showing a non-uniform peak, with an average molar mass (Mw) of 24,470 g/mol. The major monosaccharide was glucose (63.9 Mol%), followed by mannose (19.7 Mol%), and galactose (16.4 Mol%). Methylation analysis encountered derivatives that indicated the presence of a ß-d-glucan and a highly branched glucogalactomannan. CB-EPS was tested on murine macrophages to verify its immunoactivity, and the treated cells were able to produce TNF-α, IL-6, and IL-10. However, the cells did not produce superoxide anions or nitric oxide nor stimulated phagocytosis. The results demonstrated an indirect antimicrobial activity of macrophages by stimulating cytokines, showing another biotech applicability for the exopolysaccharides produced by C. brachyspora.


Assuntos
Macrófagos , Polissacarídeos , Animais , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/farmacologia , Biotecnologia
12.
Methods Mol Biol ; 2667: 159-168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37145283

RESUMO

Infections by dematiaceous fungi especially phaeohyphomycosis are an emerging group of infectious diseases worldwide with a variety of clinical presentations. The mouse model is a useful tool for studying phaeohyphomycosis, which can mimic dematiaceous fungal infections in humans. Our laboratory has successfully constructed a mouse model of subcutaneous phaeohyphomycosis and found significant phenotypic differences between Card9 knockout and wild-type mice, mirroring the increased susceptibility to this infection observed in CARD9-deficient humans. Here we describe construction of the mouse model of subcutaneous phaeohyphomycosis and related experiments. We hope that this chapter can be beneficial for the study of phaeohyphomycosis and facilitate the development of new diagnostic and therapeutic approaches.


Assuntos
Feoifomicose , Humanos , Animais , Camundongos , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Fungos , Antifúngicos/uso terapêutico , Proteínas Adaptadoras de Sinalização CARD
13.
Heliyon ; 9(5): e15773, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215835

RESUMO

Curvularia rarely causes human infections despite its ubiquity in the environment. It is most associated with allergic diseases such as chronic sinusitis and allergic bronchopulmonary mycosis; however, causing a lung mass is rarely reported in the literature. We describe an interesting case of a 57-year-old man with a history of asthma and localized prostate cancer diagnosed with a Curvularia-caused lung mass that responded quickly to itraconazole.

14.
Indian J Pathol Microbiol ; 66(2): 314-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077074

RESUMO

Objectives: Phaeohyphomycosis refers to infections caused by phaeoid/dematiaceous or darkly pigmented fungi. This study was undertaken to further increase our knowledge about the incidence of phaeohyphomycosis and its causative agents. Materials and Methods: The present study was conducted over a period of one and a half years (January 2018-June 2019) on specimens received from patients with varied clinical manifestations ranging from superficial infections, subcutaneous cysts, pneumonia, brain abscess to a disseminated infection. These specimens were processed in the Department of Microbiology for potassium hydroxide (KOH) examination and culture and in Pathology for cytology/histopathological examination (HPE). All specimens positive on direct examination for dark grey, brown or black fungi were included in the study. Results: A total of 20 specimens were confirmed as phaeohyphomycosis. Most of the patients belonged to the age group of 41 to 50 years. Male: Female ratio was 2.3:1. Trauma was the most common risk factor. Spectra of the isolated fungal pathogens comprised of Bipolaris species, Exophiala species, Curvularia geniculata, Phialemonium species, Daldinia eschscholtzii, Hypoxylon anthochroum, Phaeoacremonium species, Leptosphaerulina australis, Medicopsis romeroi, Lasiodiplodia theobromae, Eutypella species, Chaetomium globosum, Alternaria species, Cladophialophora bantiana and 2 unidentified dematiaceous fungi. Recovery from phaeohyphomycosis was seen in 12 patients, 7 were lost to follow up and one patient succumbed to the illness. Conclusion: Infections caused by phaeoid fungi can no longer be viewed as rare. In fact, phaeohyphomycosis can have myriad of presentations spanning from mild cutaneous infections to fatal brain disease. Therefore, a high index of clinical suspicion is needed to diagnose such infections. The primary treatment modality remains surgical removal of the lesion in cutaneous or subcutaneous infections however disseminated disease with a guarded prognosis requires aggressive management.


Assuntos
Encefalopatias , Feoifomicose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Feoifomicose/diagnóstico , Feoifomicose/epidemiologia , Feoifomicose/tratamento farmacológico , Pele/patologia , Atenção à Saúde , Índia/epidemiologia , Antifúngicos/uso terapêutico
15.
Ther Adv Infect Dis ; 10: 20499361231161387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051439

RESUMO

Flucytosine is an antifungal agent first licensed in the 1970's. However, its clinical value has long been overlooked and its availability across the globe is limited. This review highlights the important clinical and pharmacological aspects of flucytosine. This a narrative review of the clinical and in vitro susceptibility literature, with a focus on clinical uses for flucytosine. Detailed literature review including early literature related to primary and acquired resistance to flucytosine. Flucytosine has good antifungal activity against Cryptococcus species, Candida species, and dematiaceous fungi. Its water solubility enables good penetration into the eye, urinary tract, central nervous system (CNS), cardiac vegetations and fungal biofilms. In combination with amphotericin B, it shows early fungicidal activity against Cryptococcus species, and this translates to ~20% improved survival in cryptococcal meningitis. Combination therapy also reduces the mortality of Candida meningitis, and should be used in neonatal candidiasis because of the high frequency of CNS infection. Monotherapy for urinary candidiasis is under-studied, but is usually effective. It is probably valuable in the treatment of Candida endocarditis and endophthalmitis: there are few data. It is not effective for aspergillosis or mucormycosis. Flucytosine monotherapy of urinary candidiasis resulted in 22% developing resistance on therapy and failing therapy, and in 29% of 21 patients with cryptococcosis. Certain regions of the world still do not have access to flucytosine compromising the management of certain severe fungal infections. Flucytosine has an important role in combination therapy for yeast and dematiaceous infections and probably as monotherapy for urinary candidiasis, with a modest risk of resistance emergence. Facilitating access to flucytosine in those regions (especially low-income countries) might alleviate the mortality of invasive fungal diseases.

16.
Front Cell Infect Microbiol ; 13: 1131416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36909734

RESUMO

Introduction: Chromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition. Methods: In this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates. Results: These analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC. Discussion: Overall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.


Assuntos
Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Everolimo/uso terapêutico , Anfotericina B/farmacologia , Micoses/tratamento farmacológico , Voriconazol , Testes de Sensibilidade Microbiana , Fungos
17.
Mycoses ; 66(4): 317-330, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36527168

RESUMO

BACKGROUND: A number of recalcitrant phaeohyphomycosis cases with a life-threatening prognosis have been observed in CARD9-deficient patients, but little is known about the long-term management strategies that are effective for such intractable individuals. OBJECTIVES: To study the genetic and immunological mechanisms underlying recalcitrant phaeohyphomycosis and to share our clinical experiences regarding its treatment. PATIENTS/METHODS: Ten CARD9-deficient patients with recalcitrant phaeohyphomycosis admitted to our centre in the past two decades were followed-up, and their clinical presentations, laboratory findings, treatment and prognoses were analysed; one of them was a novel case of recalcitrant phaeohyphomycosis harbouring CARD9 mutations. Innate and adaptive immunological responses of patient-derived peripheral blood mononuclear cells were evaluated using ELISA and flow cytometry. RESULTS: We identified a total of seven CARD9 mutations in the ten analysed patients. Moreover, patient-derived cells exhibited a significant impairment of innate and adaptive immune responses upon fungus-specific stimulation. All the patients experienced recurrence and exacerbation; four of them died, two exhibited continued disease progress with unsatisfactory therapeutic efficacy, three showed obvious improvement under maintenance therapy, and only one achieved a clinical cure. CONCLUSIONS: Our study highlighted that otherwise healthy patients diagnosed with early-onset, unexplained and recalcitrant phaeohyphomycosis should be analysed for CARD9 mutations and immune deficiency. Thereafter, the length and choice of management remain challengeable and must be adjusted based on the clinical presentations and responses of patients over their lifetimes. Although continued posaconazole treatment may be the promising first-line therapy at present, novel strategies are worth exploring.


Assuntos
Feoifomicose , Humanos , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Leucócitos Mononucleares/metabolismo , Mutação , Proteínas Adaptadoras de Sinalização CARD/genética
18.
J Infect Public Health ; 16(1): 25-33, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36459708

RESUMO

PURPOSE: To investigate the dematiaceous fungal profile of patients with ocular mycoses attending a tertiary eye care hospital in Coimbatore, India METHODS: The identification of dematiaceous fungus based on their morphology, their genotypes, and the measurement of the minimum inhibitory concentrations (MICs) using microdilution method of routinely used antifungal drugs were all compared. RESULTS: A total of 148 dematiaceous fungi were isolated during a study period of 27 months. Isolates were confirmed as Curvularia spp. (n = 98), Exserohilum spp. (n = 32), Alternaria spp. (n = 14), Exophiala spp. (n = 2), Cladosporium sp. (n = 1) and Aureobasidium sp. (n = 1). Out of 50 well grown isolates characterized genotypically based on the amplification and sequencing of the ITS region of the ribosomal RNA gene cluster and subsequent BLAST analysis, Curvularia lunata (n = 24), C. aeria (n = 1), C. spicifera (n = 8), C. hawaiiensis (n = 1), C. maydis (n = 2), C. papendorfii (n = 2), C. geniculata (n = 3), C. tetramera (n = 2) and Exs. rostratum (n = 7) were identified. In vitro antifungal susceptibilities of the most tested dematiaceous isolates showed that voriconazole had a MIC50 of 0.25 µg ml-1, while amphotericin B had a MIC50 of 0.25 µg ml-1 for Curvularia spp. and Alternaria spp. CONCLUSION: Voriconazole proved to be the most effective drug against the pigmented filamentous fungi, followed by amphotericin B, itraconazole and econazole.


Assuntos
Antifúngicos , Infecções Oculares Fúngicas , Humanos , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Voriconazol/farmacologia , Voriconazol/uso terapêutico , Filogenia , Infecções Oculares Fúngicas/microbiologia , Fungos , Testes de Sensibilidade Microbiana
19.
J Orthop Case Rep ; 13(12): 71-74, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38162370

RESUMO

Introduction: Dematiaceous fungi are a group of fungi characterized by the presence of melanin in their cell walls. These fungi are known to cause a wide range of infections in humans, including skin and soft-tissue infections, sinusitis, and meningitis. Infections caused by dematiaceous fungi are typically seen in immunocompromised hosts and manifest most commonly as cutaneous or subcutaneous disease. Systemic infections are exceedingly rare and associated with significant morbidity and mortality. Case Report: Here is a case study of a 75-year-old diabetic male with a rare case of dematiaceous fungal infection in the olecranon bursa. The patient presented with a painless swelling of 3-year duration over the right elbow which started draining pus for 1 month. Surgical excision of the bursa was performed, and histopathological examination and culture confirmed the diagnosis of dematiaceous fungal infection. We discuss the diagnosis, treatment, and management of this rare fungal infection. Conclusion: Although dematiaceous fungal infections are a rare cause of olecranon bursitis, the clinician must send a fungal culture in every case for prompt diagnosis and treatment.

20.
J Clin Med ; 11(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36143037

RESUMO

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.

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