Candida albicans skin infection in diabetic patients: An updated review of pathogenesis and management.

Candida species, commensal residents of human skin, are recognized as the cause of cutaneous candidiasis across various body surfaces. Individuals with weakened immune systems, particularly those with immunosuppressive conditions, are significantly more susceptible to this infection. Diabetes mellitus, a major metabolic disorder, has emerged as a critical factor inducing immunosuppression, thereby facilitating Candida colonization and subsequent skin infections. This comprehensive review examines the prevalence of different types of Candida albicans-induced cutaneous candidiasis in diabetic patients. It explores the underlying mechanisms of pathogenicity and offers insights into recommended preventive measures and treatment strategies. Diabetes notably increases vulnerability to oral and oesophageal candidiasis. Additionally, it can precipitate vulvovaginal candidiasis in females, Candida balanitis in males, and diaper candidiasis in young children with diabetes. Diabetic individuals may also experience candidal infections on their nails, hands and feet. Notably, diabetes appears to be a risk factor for intertrigo syndrome in obese individuals and periodontal disorders in denture wearers. In conclusion, the intricate relationship between diabetes and cutaneous candidiasis necessitates a comprehensive understanding to strategize effective management planning. Further investigation and interdisciplinary collaborative efforts are crucial to address this multifaceted challenge and uncover novel approaches for the treatment, management and prevention of both health conditions, including the development of safer and more effective antifungal agents.

Miconazole nitrate bearing ultraflexible liposomes for the treatment of fungal infection.

Miconazole nitrate is a widely used antifungal agent, but its use in topical formulations is not efficacious because deep seated fungal infections are difficult to treat with conventional topical formulation. Miconazole nitrate loaded ultraflexible liposomes have been prepared and their topical performance has been compared with conventional liposomes containing miconazole nitrate. Various ultraflexible liposomal formulations were prepared and extensively characterized for vesicular shape, size, entrapment efficiency, degree of deformability and in-vitro skin permeation through rat skin. Higher rate of drug transfer across the skin with ultraflexible liposomal formulations of miconazole nitrate suggests that the drug in its lipo-solubilized state might have gained facilitated entry into the tough barrier consisting of subcutaneous. In-vivo study showed better antifungal activity as compared to traditional liposomes and plain drug solution. This was confirmed through fluoroscence microscopy. It is concluded that prepared ultraflexible liposomes can facilitate improved and localized drug action in the skin, thus providing a better option to deal with deep seated skin problems.

Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization.

Cutaneous candidiasis is a common topical fungal infection which may be more prominent in patients associated with AIDS. It is usually treated by conventional formulations such as cream, gel, which show various adverse effects on skin along with systemic absorption. To overcome these drawbacks, various novel drug delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based microparticulate systems have shown good dermal penetration after topical application. Therefore, in the present study clotrimazole-loaded PLGA microspheres were prepared for targeted dermal delivery. Microspheres were prepared by using a single emulsification (oil-in-water, O/W) evaporation technique and characterized for different parameters. Prepared microparticulate systems were dispersed in Carbopol 934® gel and antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed guinea pigs. Particle size of optimized formulation was 2.9 µm along with 74.85% entrapment of drug. Skin retention studies revealed that drug accumulation in the skin was higher with microspheres gel as compared to marketed gel. Confocal microscopy of skin further confirmed penetration of microspheres up to 50 µm into the dermal region. In-vivo antifungal activity studies demonstrated that microsphere gel showed better therapeutic activity, lowest number of cfu/ml was recorded, as compared to marketed gel after 96 h of application. Based on the results of the study, it can be concluded that PLGA microparticles may be promising carriers to deliver clotrimazole intradermally for the treatment of invasive fungal infections.

Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis.

The localized delivery of fluconazole (FLZ) by conventional therapy is a major impediment in achieving its therapeutic efficacy against skin infections, such as cutaneous candidiasis. Therefore, the present study was aimed to develop FLZ-loaded vesicular construct(s), such as liposomes and niosomes, incorporated into carbopol gel (1%; w/w) for sustained, localized application. The liposomes and niosomes were prepared by the lipid/nonionic surfactant-based dry-film hydration method and were characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that the size of liposomes and niosomes was found to be 0.348 ± 0.054 and 0.326 ± 0.033 µm with encapsulation efficiency of 31.8 ± 1.36 and 27.6 ± 1.08%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments showed significantly higher accumulation of drug in the case of liposomal gel. The in vivo localization studies in viable skin showed that liposomal gel could produce 14.2-fold higher drug accumulation, compared with plain gel, while it was 3.3-fold more in the case of an equivalent-dose application in the form of niosomal gel. The antifungal study also confirmed the maximum therapeutic efficacy of liposomal gel, as the lowest number of cfu/mL was recorded following liposomal FLZ application. The studies signify the potential of liposomal gel for topical delivery of FLZ with increased accumulation of drug in various strata of skin vis-a-vis through sustained release of drug could maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.

Physically cross-linked polyvinyl alcohol for the topical delivery of fluconazole.

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze-thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 x 4 x 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis.

BACKGROUND: Dual-release mechanism of ethosomal gels (ie, ethosomes and gel) makes them as versatile drug delivery systems for topical applications. Clove oil is obtained from the clove buds exhibited broad antifungal and antibacterial activity. Cutaneous candidiasis is the infection caused by Candida albicans or other Candida species. AIM: The aim of the present study was to prepare ethosomal gel of clove oil and evaluate its effectiveness in the treatment of cutaneous candidiasis. METHODS: Ethosomes of clove oil was formulated by using varying concentrations of soyaphosphotidyl choline and ethanol, and later, it was incorporated into carbapol 974 base gels to form ethosomal gel. The prepared ethosomal gels were also evaluated for spreadability, drug release studies, ex vivo permeation study, and antifungal activity. RESULTS: The optimized formulation did not cause any irritation to the skin since the pH of formulation was in the pH range of skin. The ethosomal gel showed satisfactory antifungal activity against the fungus C. albicans compared to pure clove oil. CONCLUSIONS: The results showed that developed formulation could be promising one in the topical delivery of clove oil for the treatment of cutaneous candidiasis.

[Candida in dermatology]. / Candida in der Dermatologie.

Regarding Candida in dermatology, two pathogenetic pathways must be taken into account: 1. on infection of the skin 2. immunological reactions with skin alterations as a result of Candida infection or colonization in the mouth and/or intestine. Case reports describe typical situations of napkin dermatitis, intertriginous candidosis, the intrauterine Candida infection of the foetus, Candida granuloma, Candida folliculitis and Candida paronychia. In the second part results of investigations of patients suffering from psoriasis, atopic dermatitis and urticaria are presented. There were no differences in the colonization with Candida albicans and in the level of Candida antibody titres between patients and a healthy control group.

Treatment of chronic mucocutaneous candidosis with ketoconazole: a study of 12 cases.

Twelve patients with chronic mucocutaneous candidosis were treated orally with ketoconazole (doses, 200-400 mg daily) for a mean period of six months. Seven of the patients had one of the following abnormalities: congenital endocrinopathy syndrome, an autosomal recessive or autosomal dominant defect in which candidosis is not associated with endocrinopathy, or the malabsorption syndrome. All patients had fungal infections of the mouth, and 11 had onychomycosis. Two patients were also infected with dermatophytes. At the end of treatment, 10 patients were cured of oral infection, and 11 with nail infections showed significant improvement. Marked improvement of hand and foot infections was also recorded. Patients infected with dermatophyte fungi had the poorest responses to therapy. The mean (+/- SD) MIC for isolates of Candida albicans from eight patients was 0.95 (+/- 0.78) microgram/ml. Clinical and biochemical monitoring showed no toxicity, and no resistant fungi emerged during treatment. Results of this initial study of ketoconazole for treatment of severe and recalcitrant superficial infections indicate the need for further assessment of this drug, which appears to offer a simple, nontoxic, and effective treatment of fungal infections.

Cimetidine as an immunomodulator: chronic mucocutaneous candidiasis as a model.

Four adult patients with chronic mucocutaneous candidiasis were studied to establish a possible role for cimetidine as an immunomodulator. These patients had negative baseline in-vivo and in-vitro cell-mediated immune response to candida antigen as measured by intradermal skin tests, lymphocyte transformation, and leukocyte migration inhibitory factor production to cimetidine, 300 mg by mouth, four times daily. Subsequently four of four patients developed strong (greater than 15 mm) intradermal skin test reactions, and two of four patients produced leukocyte migration inhibitory factor to candida antigen. Skin tests and leukocyte migration inhibitory factor production reverted to baseline negative values when repeated 4 weeks after discontinuation of therapy. After 4 additional weeks on cimetidine, four of four patients showed strong positive skin tests and leukocyte migration inhibitory factor production to candida antigen. Lymphocyte transformation was not affected by therapy.

[Partial deficiency of cell-mediated immunity in a child with chronic mucocutaneous candidiasis. Intercurrent meningeal and pulmonary cryptococcosis]. / Déficit partiel de l'immunité à médiation cellulaire chez un enfant atteint de candidose cutanéomuqueuse chronique. Cryptococcose pulmonaire et méningée intercurrente

The authors report a new case of partial immune deficiency of cellular immunity, associated with chronic mucocutaneous candidiasis in a 12 Years-old boy. The disease began very early during the first few weeks of life, with thrush in the mouth. This candidiasis then evolved intermittently and was still present. Numerous cutaneous, pulmonary and ear infections occured throughout this child's life. This morbid association led to a search for an immune deficiency. Humoral immunity was normal. Abnormalities of cellular immunity were as follows: apart from candidine skin anergy, there was a deficiency in the factor which inhibits leukocyte migration, secretion of a factor favouring this migration (MEF). It was also noted the presence of the patient's serum, of a factor inhibiting lymphocyte transformation in the presence of candidine. In spite of treatment with intravenous route, amphotericin B, followed by transfer factor, the oral candidiasis persisted together with the skin anergy to candidine. On the other hand, the serum inhibitory factor disappeared. Pulmonary cryptococcosis probably favoured by corticosteroid treatment, developed on this background of immune deficiency; as usual it spread to the meninges. Treatment associating intraveinous amphotericin B and 5 fluorocytosine oral and later intravenous, total duration 6 months, grave a recovery maintained on a 8 months follow up.

[Clotrimazol in the treatment of candida infections in premature and newborn children (author's transl)]. / Clotrimazol in der Behandlung von Soorinfektionen auf Früh- und Neugeborenenstationen

The early infancy is especially affected by moniliasis in pediatrics. The causes are: broad spread of Candida albicans in the environment of these children, a growing immunity, the immaturity of the skin and an insufficient candida-static activity of the serum. The prematures and the newborns with an irregular birth are especially endangered. This danger is increased by simultaneous antibiotic therapy. The arising mycosis can reach from the relative harmless mouth- and diaper-thrush to serious septic diseases. An effective therapy therefore is very much desired. As new efficacious medicaments the derivates of imidazol, Clotrimazol, have proved satisfactory for the treatment of mycoses. It is as Canesten marketed. The drug possesses a strong activity against numerous fungi, some protozoa, and bacteria. In this paper it is reported on own pharmacokinetic and therapeutic investigations with Clotrimazol. The substance has been very useful for the treatment of mouth- and diaper-thrush. Clotrimazol was administered as BAYb 5097 peroral and local as Canesten -solution 1% and -cream 1%. There were 171 treatments carried out. Essential side-effects were not observed.

[New developments in medical mycology]. / Neue Entwicklungen in der medizinischen Mykologie.

Not only have the systemic mycoses clearly increased in number but also mycoses of the skin are more common than presumed in the past. Today onychomycosis is found in up to 10% of human beings. Onychomycosis can compromise quality of life markedly. Common tinea pedis is one of the most important risk factors for erysipelas of the lower legs. The clinical presentation of oral candidosis in HIV-infected patients is changing; Candida dubliniensis has been identified as another important causative microorganism. Onychomycosis today in most cases can be cured using terbinafine or itraconazole. When choosing the ideal drug in a given case, both the benefit risk ratio and the benefit cost ratio have to be taken into account. Liposomally encapsulated amphotericin B represents a major breakthrough in the treatment of systemic mycoses or fever of unknown origin. The same applies to liposomally encapsulated econazole with respect to tinea pedis. In regard to the pathogenesis of Candida infections the family of secreted aspartic proteinases plays a major role as a virulence factor and possible future target for antimycotic treatment.