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1.
Mycoses ; 67(6): e13751, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825584

ABSTRACT

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.


Subject(s)
Antifungal Agents , Itraconazole , Microsporum , Tinea Capitis , Humans , Child, Preschool , Antifungal Agents/therapeutic use , Male , Female , Tinea Capitis/drug therapy , Tinea Capitis/epidemiology , Tinea Capitis/microbiology , Itraconazole/therapeutic use , China/epidemiology , Microsporum/isolation & purification , Child , Infant , Glucocorticoids/therapeutic use , Treatment Outcome , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/microbiology , Risk Factors , Adolescent , Adult , Middle Aged , Retrospective Studies
2.
Acta Trop ; 255: 107237, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723739

ABSTRACT

The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased incidence of dermatophytosis among feline companions. Despite this growing concern, there is a noticeable scarcity of studies in India delving into the etiological factors contributing to dermatophytosis in cats. This disease is a threat to animal health and carries public health significance, given that cats are recognized reservoir hosts for Microsporum canis, a common dermatophyte affecting humans and animals. This study endeavours to identify the dermatophytes affecting cats and establish a standardized therapeutic regimen while accounting for the local stigma surrounding the regular bathing of cats. The study involved the examination of 82 cats presenting dermatological lesions, when subjected to cultural examination in dermatophyte test medium revealed 36 afflicted with dermatophytes. Isolates were presumptively identified by staining using lactophenol cotton blue, Chicago sky blue 6B, and Calcofluor white stains. Molecular-level identification of the isolates was confirmed through PCR-RFLP, amplifying the Internal Transcribed Spacer Sequence of 16 s rDNA, followed by restriction digestion using the Mva1 enzyme. Among the thirty-six isolates, 29 were identified as M. canis, while the remaining 7 were M. gypseum. The cases were categorized into five groups and treated with Lime Sulphur dip, 4 % chlorhexidine shampoo, a shampoo containing 2 % miconazole and 4 % chlorhexidine, oral itraconazole alone, and a combination of oral itraconazole with lime-Sulphur dip. Statistical analysis revealed that the response was notably swifter with lime Sulphur dip when considering only topical therapy. Moreover, the mycological cure was most expeditious when combining Lime Sulphur dip with oral itraconazole. These findings underscore the pivotal role of topical biocides in feline dermatophytosis treatment, potentially reducing the reliance on specific antifungals and thereby contributing to the mitigation of antimicrobial resistance emergence.


Subject(s)
Antifungal Agents , Cat Diseases , Microsporum , Tinea , Cats/microbiology , Animals , Cat Diseases/microbiology , Cat Diseases/drug therapy , India/epidemiology , Tinea/veterinary , Tinea/microbiology , Tinea/drug therapy , Tinea/epidemiology , Antifungal Agents/therapeutic use , Microsporum/isolation & purification , Microsporum/genetics , Male , Female , Arthrodermataceae/isolation & purification , Arthrodermataceae/genetics , Arthrodermataceae/classification , Arthrodermataceae/drug effects , Itraconazole/therapeutic use , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , DNA, Fungal/genetics , DNA, Ribosomal Spacer/genetics
3.
Mycoses ; 67(4): e13724, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38584320

ABSTRACT

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.


Subject(s)
Sporothrix , Sporotrichosis , Aged , Middle Aged , Humans , Female , Itraconazole/pharmacology , Itraconazole/therapeutic use , Sporotrichosis/microbiology , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Terbinafine/therapeutic use , Retrospective Studies , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Sporothrix/genetics , China/epidemiology
4.
Microbiol Spectr ; 12(6): e0396723, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38647345

ABSTRACT

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.


Subject(s)
Antifungal Agents , Cat Diseases , Drug Therapy, Combination , Itraconazole , Sporothrix , Sporotrichosis , Cats , Animals , Itraconazole/therapeutic use , Itraconazole/administration & dosage , Itraconazole/pharmacology , Sporotrichosis/drug therapy , Sporotrichosis/veterinary , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/administration & dosage , Cat Diseases/drug therapy , Cat Diseases/microbiology , Sporothrix/drug effects , Hydrazones/therapeutic use , Hydrazones/pharmacology , Female , Male , Microbial Sensitivity Tests , Biofilms/drug effects , Treatment Outcome
5.
Expert Opin Pharmacother ; 25(5): 511-519, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38623728

ABSTRACT

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.


Subject(s)
Antifungal Agents , Arthrodermataceae , Drug Resistance, Fungal , Microbial Sensitivity Tests , Mutation , Terbinafine , Tinea , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Humans , Drug Resistance, Fungal/genetics , Tinea/drug therapy , Tinea/microbiology , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Terbinafine/pharmacology , Terbinafine/therapeutic use , Itraconazole/pharmacology , Itraconazole/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology
6.
Med Mycol ; 62(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38533658

ABSTRACT

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.


Subject(s)
Chromoblastomycosis , Mycoses , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Flucytosine/pharmacology , Itraconazole/pharmacology , Itraconazole/therapeutic use , Fungi , Chromoblastomycosis/microbiology , Chromoblastomycosis/veterinary , Mycoses/drug therapy , Mycoses/veterinary , Microbial Sensitivity Tests/veterinary
7.
BMJ Case Rep ; 17(3)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38458767

ABSTRACT

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent as Fusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy. F. falciforme has been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.


Subject(s)
Fusarium , Mycetoma , Male , Humans , Mycetoma/diagnosis , Mycetoma/drug therapy , Neglected Diseases , Itraconazole/therapeutic use
8.
BMJ Case Rep ; 17(3)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38490708

ABSTRACT

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.


Subject(s)
Ascomycota , Chromoblastomycosis , Male , Humans , Terbinafine/therapeutic use , Itraconazole/therapeutic use , Chromoblastomycosis/diagnosis , Chromoblastomycosis/drug therapy , Chromoblastomycosis/microbiology , Buttocks/pathology , Antifungal Agents/therapeutic use
9.
J Mycol Med ; 34(2): 101474, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38484562

ABSTRACT

Histoplasmosis is a mycosis due to a dimorphic fungus Histoplasma capsulatum. This study aimed at providing an overview of histoplasmosis epidemiological, clinical, diagnostic, and therapeutic aspects from the last 30 years. This review was carried out using a systematic literature search on histoplasmosis from 1992 to 2021. We describe the clinical features, diagnostic methods and treatment. Empirical searches were conducted via the databases PubMed, Google Scholar and Science Direct. Between 1992 and 2021, 190 manuscripts were published and reported 212 cases of histoplasmosis. These publications included 115 and 97 cases of American and African histoplasmosis respectively. The number of publications increased over the last ten years with a maximum in 2020 (12.34 % of the cases reported). The disseminated forms of histoplasmosis were the most frequently reported cases as compared to the localized forms. This was the case with the American histoplasmosis (75.65 %) as well as with the African histoplasmosis (55.67 %). Itraconazole (31.17 %) and Amphotericin B (26.62 %) were the most used drugs in the management of these cases. American histoplasmosis is distributed worldwide whereas African histoplasmosis is mainly present in intertropical Africa. There is a critical need for setting up a global surveillance system, towards a better understanding of the disease.


Subject(s)
Antifungal Agents , Histoplasma , Histoplasmosis , Itraconazole , Histoplasmosis/epidemiology , Histoplasmosis/diagnosis , Histoplasmosis/drug therapy , Humans , Histoplasma/isolation & purification , Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Amphotericin B/therapeutic use , Africa/epidemiology
10.
J Mycol Med ; 34(2): 101473, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38493607

ABSTRACT

Diagnosis and management of fungal infections are challenging in both animals and humans, especially in immunologically weakened hosts. Due to its broad spectrum and safety profile when compared to other antifungals, itraconazole (ITZ) has been widely used in the treatment and prophylaxis of fungal infections, both in human and veterinary medicine. The dose and duration of management depend on factors such as the type of fungal pathogen, the site of infection, sensitivity to ITZ, chronic stages of the disease, the health status of the hosts, pharmacological interactions with other medications and the therapeutic protocol used. In veterinary practice, ITZ doses generally vary between 3 mg/kg and 50 mg/kg, once or twice a day. In humans, doses usually vary between 100 and 400 mg/day. As human and veterinary fungal infections are increasingly associated, and ITZ is one of the main medications used, this review addresses relevant aspects related to the use of this drug in both clinics, including case reports and different clinical aspects available in the literature.


Subject(s)
Antifungal Agents , Itraconazole , Mycoses , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Itraconazole/therapeutic use , Mycoses/drug therapy , Mycoses/veterinary , Mycoses/microbiology , Animals , Veterinary Medicine/methods
11.
Emerg Infect Dis ; 30(4): 807-809, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38437706

ABSTRACT

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.


Subject(s)
Antifungal Agents , Trichophyton , Female , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Drug Resistance, Fungal , Itraconazole/therapeutic use , Microbial Sensitivity Tests , Terbinafine/pharmacology , Terbinafine/therapeutic use
12.
Am J Trop Med Hyg ; 110(5): 965-967, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38531098

ABSTRACT

Tinea capitis is a common fungal infection caused by dermatophytes in children, but it is rare in infants. Although oral itraconazole has been widely used to treat tinea capitis, its use in infants is limited due to its low prevalence in this age group. A previous study reported the effectiveness of itraconazole continuous therapy in treating infantile tinea capitis caused by Microsporum canis. However, this approach has not been extended to tinea capitis caused by other fungi. In this study, we present four cases of infantile tinea capitis treated with continuous itraconazole oral solution therapy (5 mg/kg/day). Two patients were infected with M. canis, one patient with Nannizzia gypsea, and another with Trichophyton tonsurans. This study assesses the efficacy and safety of itraconazole oral solution continuous therapy, expanding our understanding by demonstrating its effectiveness for infantile tinea capitis caused by T. tonsurans and N. gypsea.


Subject(s)
Antifungal Agents , Itraconazole , Tinea Capitis , Humans , Itraconazole/therapeutic use , Itraconazole/administration & dosage , Tinea Capitis/drug therapy , Tinea Capitis/microbiology , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Infant , Male , Female , Administration, Oral , Microsporum/drug effects , Treatment Outcome
13.
Eur Respir J ; 63(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38423624

ABSTRACT

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.


Subject(s)
Aspergillosis, Allergic Bronchopulmonary , Invasive Pulmonary Aspergillosis , Adult , Child , Humans , Aspergillosis, Allergic Bronchopulmonary/diagnosis , Aspergillosis, Allergic Bronchopulmonary/drug therapy , Immunoglobulin E , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Itraconazole/therapeutic use , Mycology , Prednisolone
14.
Cancer Sci ; 115(4): 1154-1169, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38278779

ABSTRACT

Advanced colorectal cancer (CRC) is characterized by a high recurrence and metastasis rate, which is the primary cause of patient mortality. Unfortunately, effective anti-cancer drugs for CRC are still lacking in clinical practice. We screened FDA-approved drugs by utilizing targeted organoid sequencing data and found that the antifungal drug itraconazole had a potential therapeutic effect on CRC tumors. However, the effect and mechanism of itraconazole on CRC tumors have not been investigated. A cell line-derived xenograft model in tumor-bearing mice was established and single-cell RNA sequencing was performed on tumor samples from four mice with or without itraconazole treatment. The proportion of cell populations and gene expression profiles was significantly different between the two groups. We found that itraconazole could inhibit tumor growth and glycolysis. We revealed that CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression. Clinical analysis showed that CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival. In summary, itraconazole treatment remodeled cell composition and gene expression profiles. Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB-ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.


Subject(s)
Colorectal Neoplasms , Itraconazole , Humans , Animals , Mice , Itraconazole/pharmacology , Itraconazole/therapeutic use , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease Models, Animal , Glycolysis , Cell Proliferation , Gene Expression Regulation, Neoplastic , CCAAT-Enhancer-Binding Protein-beta/genetics
15.
Vet Dermatol ; 35(3): 284-295, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38169074

ABSTRACT

BACKGROUND: No reports have compared the clinical therapeutic efficacy of fluconazole and itraconazole in canine Malassezia dermatitis. OBJECTIVES: The study aimed to compare the clinical therapeutic efficacy of fluconazole and itraconazole and to evaluate the adverse effects of fluconazole in canine Malassezia dermatitis. ANIMALS: Sixty-one client-owned dogs with Malassezia dermatitis. MATERIALS AND METHODS: The enrolled animals were randomly divided into groups receiving 5 mg/kg fluconazole (5FZ), 10 mg/kg fluconazole (10FZ) or 5 mg/kg itraconazole (5IZ). The drugs were orally administered once daily for 28 days. Cytological examination, clinical index score (CIS), pruritus Visual Analog Scale (PVAS) evaluation and blood analysis (for 5FZ only) were performed on Day (D)0, D14 and D28. RESULTS: On D14, significant reductions in mean yeast count (MYC), CIS and PVAS were observed in the 5FZ (n = 20, p < 0.01), 10FZ (n = 17, p < 0.01) and 5IZ (n = 16, p < 0.05) groups. In all three groups, a significant reduction (p < 0.001) in MYC, CIS and PVAS expression was observed on D28. There was no significant difference in the percentage reduction of MYC, CIS and PVAS among the groups. Moreover, there was a significant difference (p < 0.05) in each group between D14 and D28, except for the percentage reduction in MYC in the 10FZ and 5IZ groups. No adverse effects of fluconazole were observed in the 5FZ or 10FZ groups. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that 5FZ and 10FZ are as effective as itraconazole in canine Malassezia dermatitis.


Subject(s)
Antifungal Agents , Dermatomycoses , Dog Diseases , Fluconazole , Itraconazole , Malassezia , Animals , Dogs , Itraconazole/therapeutic use , Itraconazole/administration & dosage , Dog Diseases/drug therapy , Dog Diseases/microbiology , Fluconazole/therapeutic use , Fluconazole/administration & dosage , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Malassezia/drug effects , Male , Female , Dermatomycoses/veterinary , Dermatomycoses/drug therapy , Single-Blind Method , Treatment Outcome
16.
Pathol Res Pract ; 253: 155086, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38176308

ABSTRACT

Liver cancer stands as the fourth leading global cause of death, and its prognosis remains grim due to the limited effectiveness of current medical interventions. Among the various pathways implicated in the development of hepatocellular carcinoma (HCC), the hedgehog signaling pathway has emerged as a crucial player. Itraconazole, a relatively safe and cost-effective antifungal medication, has gained attention for its potential as an anticancer agent. Its primary mode of action involves inhibiting the hedgehog pathway, yet its impact on HCC has not been elucidated. The main objective of this study was to investigate the effect of itraconazole on diethylnitrosamine-induced early-stage HCC in rats. Our findings revealed that itraconazole exhibited a multifaceted arsenal against HCC by downregulating the expression of key components of the hedgehog pathway, shh, smoothened (SMO), and GLI family zinc finger 1 (GLI1), and GLI2. Additionally, itraconazole extended survival and improved liver tissue structure, attributed mainly to its inhibitory effects on hedgehog signaling. Besides, itraconazole demonstrated a regulatory effect on Notch1, and Wnt/ß-catenin signaling molecules. Consequently, itraconazole displayed diverse anticancer properties, including anti-inflammatory, antiangiogenic, antiproliferative, and apoptotic effects, as well as the potential to induce autophagy. Moreover, itraconazole exhibited a promise to impede the transformation of epithelial cells into a more mesenchymal-like phenotype. Overall, this study emphasizes the significance of targeting the hedgehog pathway with itraconazole as a promising avenue for further exploration in clinical studies related to HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Rats , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Hedgehog Proteins/genetics , Itraconazole/pharmacology , Itraconazole/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Wnt Signaling Pathway
17.
J Am Anim Hosp Assoc ; 60(1): 40-44, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38175979

ABSTRACT

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.


Subject(s)
Blastomycosis , Cat Diseases , Cats , Male , Animals , Blastomycosis/complications , Blastomycosis/diagnosis , Blastomycosis/drug therapy , Blastomycosis/veterinary , Epistaxis/etiology , Epistaxis/veterinary , Epistaxis/drug therapy , Blastomyces , Itraconazole/therapeutic use , Nasal Cavity , Antifungal Agents/therapeutic use , Cat Diseases/diagnosis , Cat Diseases/drug therapy
18.
Mycopathologia ; 189(1): 12, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38231359

ABSTRACT

Basidiobolomycosis is an uncommon fungal infection caused by the genus Basidiobolus. In immunocompetent children, it usually causes cutaneous infection and rarely affects the gastrointestinal tract, and it is extremely rare for the disease to spread. The present study reports the first case of disseminated basidiobolomycosis caused by Basidiobolus omanensis in a child with acute lymphoblastic leukemia who died as a result of uncontrolled infection and multi-organ failure despite surgical and antifungal therapy with L-AMB and voriconazole. A review of the literature yielded 76 cases, including the current case with the majority of which were reported as invasive gastrointestinal infection. The median age was 4 years (61 male and 15 female) and the majority of these children were from the Middle East (80%), specifically Saudi Arabia (45%). Most patients were treated with systemic antifungal agents (mostly itraconazole and amphotericin B). Surgical intervention was done in 25% of these patients and the death rate was 12%.


Subject(s)
Entomophthorales , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Zygomycosis , Child , Humans , Female , Male , Child, Preschool , Zygomycosis/diagnosis , Zygomycosis/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Itraconazole/therapeutic use
19.
Mycoses ; 67(1): e13690, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38214347

ABSTRACT

BACKGROUND: Treatment of onychomycosis is still challenging and warrants the development of new treatment strategies. Different trials were conducted to increase the penetration and efficacy of topical antifungals aiming at finding an alternative treatment especially when systemic antifungals are contraindicated. OBJECTIVES: To evaluate the efficacy of trichloroacetic acid (TCA) 100% either alone or combined with topical tioconazole 28% versus itraconazole pulse therapy in the treatment of onychomycosis. PATIENTS/METHODS: Forty-five patients with onychomycosis were divided into three groups: group (A) treated by topical TCA 100% for 12 sessions, group (B) treated by TCA 100% for 12 sessions combined with topical tioconazole 28% for 18 weeks and group (C) treated by itraconazole (400 mg/day for 1 week/month for 4 months). RESULTS: TCA 100% combined with topical tioconazole 28% showed the highest therapeutic response; however, the difference between the groups was statistically insignificant. Mycological cure (negative culture) was reported in 66.7% of group B versus 60% of group A and 40% of group C at the 20 week. CONCLUSIONS: TCA 100% is an effective and safe treatment option for onychomycosis especially when combined with antifungals. This modality is promising in the treatment of onychomycosis especially with the increased resistance to different antifungals.


Subject(s)
Foot Dermatoses , Imidazoles , Onychomycosis , Humans , Itraconazole/therapeutic use , Onychomycosis/drug therapy , Antifungal Agents/therapeutic use , Trichloroacetic Acid/therapeutic use , Treatment Outcome , Foot Dermatoses/drug therapy
20.
Mycoses ; 67(1): e13681, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38214352

ABSTRACT

BACKGROUND: The present epidemic of dermatophytosis in India is marked by an increase in chronic, recurrent and disseminated cases. A combination of oral itraconazole and topical luliconazole is being increasingly utilised by dermatologists in India. The superiority of this combination is not supported by robust clinical trial data. OBJECTIVE: We conducted this randomised, open-label, two arms, parallel assignment intervention trial between November 2022 and May 2023 to determine the superiority of topical 1% Luliconazole over bland emollient as adjuvant to systemic Itraconazole therapy in the management of dermatophytosis. METHOD: In this study, 135 patients of either sex were randomised to two study cohorts. Major exclusions being concomitant medical illness, use of concomitant medication and substance abuse. Participants were randomly assigned to receive topical bland emollient, (Cohort I, n = 67) or topical luliconazole, (Cohort II, n = 68). Both cohorts received oral itraconazole 200 mg/day (100 mg BID) and levocetirizine 5 mg twice a day as a systemic regime. Clinical and mycological cure at the end of 6 weeks and clinical relapse among cure patients during 10-week follow-up were observed. RESULTS: The cure rates for Cohorts I and II at 6 weeks were 50 (74.62%) and 56 (82.35%), (p = .46), respectively. During the 4-week follow-up period, clinical relapses were observed in 16 (32%) of the 50 patients in Cohort I and 12 (21.43%) of the 56 patients in Cohort II (p = .18). Luliconazole cohort shows a significantly higher medical cost (p < .05). CONCLUSION: Our study shows a similar cure rate and relapse rate for patients receiving topical Luliconazole versus topical bland emollient as an adjuvant to the systemic itraconazole regime.


Subject(s)
Imidazoles , Itraconazole , Tinea , Humans , Itraconazole/therapeutic use , Antifungal Agents/therapeutic use , Emollients/therapeutic use , Tinea/drug therapy , Recurrence
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