Clioquinol influences cell membrane, attenuates virulence factors, induces apoptosis to inhibit Candida albicans growth.

Aim: To investigate the antifungal mechanism of clioquinol and indicate that clioquinol has potential as a novel therapeutic antifungal agent.Materials & methods: Analyze differentially expressed genes of Candida albicans treated with clioquinol using RNA-sequencing. The effects on cell wall and membrane features, virulence factors, apoptosis-induced cell death were also investigated.Results: The differentially expressed genes of C. albicans after treated with clioquinol focused on cell wall and membrane synthesis, antioxidant system and energy metabolism. Clioquinol did not change cell wall components levels while it decreased squalene epoxidase activity to influence the ergosterol biosynthesis in cell membrane. It also decreased cellular surface hydrophobicity and induced ß-glucan unmasking to attenuate virulence factors. Meanwhile, clioquinol influenced enzyme activities involved in antioxidant system, citrate cycle, oxidative phosphorylation and decreased the ATP levels. Clioquinol induced apoptosis in C. albicans to exert its fungicidal activity. It induced reactive oxygen species and calcium ion elevation, leading to loss of mitochondrial membrane potential, cytochrome C release, metacaspase activation, thereby triggering apoptosis.Conclusion: Clioquinol exerted anti-C. albicans activity through influencing cell membrane, attenuating virulence factors and inducing apoptosis.

[Box: see text].

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

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.

Disasters pile up on the rubbing heel: Sporothrix globosa as secondary infection to Mycobacterium chelonae infection.

Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.

Itraconazole Oral Solution for Infantile Complicated Hemangioma with Double Lesions on the Skin and One Inside the Liver.

An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.

Oral treatment with 10% potassium iodide solution for refractory cutaneous-disseminated sporotrichosis in an immunocompetent adult: Case report.

Sporotrichosis has multiple clinical manifestations, and its cutaneous-disseminated form is uncommon and, in most cases, related to immunosuppressive conditions. We report the case of a 47-year-old male patient who presented with multiple cutaneous nodules and ulcers on the left upper limb and the right thigh, with no other comorbidities. Until the diagnosis was confirmed, the patient was initially given empiric antifungal treatment with itraconazole, which showed unsatisfactory results at a local hospital. Then, he was treated with voriconazole, which led to the slow improvement of his skin lesions. At one point during the voriconazole treatment course, the patient briefly self-discontinued voriconazole for economic reasons, and the lesions recurred and worsened. The patient was finally diagnosed with cutaneous-disseminated sporotrichosis based on the isolation and identification of Sporothrix globosa. Susceptibility testing revealed that the isolate was resistant to itraconazole, fluconazole, voriconazole, terbinafine, and amphotericin. Considering the patient's poor financial condition, potassium iodide was administered. After 1-month of therapy with potassium iodide, he reported rapid improvement of his skin lesions. The patient continued potassium iodide treatment for another 5 months until the full resolution of lesions was achieved.

Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered combinational photodynamic therapy.

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.