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.

Naringenin-Capped Silver Nanoparticles Amalgamated Gel for the Treatment of Cutaneous Candidiasis.

The current research was aimed to synthesize a phytomolecule, naringenin (NRG)-mediated silver nanoparticles (NRG-SNPs) to study their antifungal potential against Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The NRG-SNPs were synthesized by using NRG as a reducing agent. The synthesis of NRG-SNPs was confirmed by a color change and surface plasmon resonance (SPR) peak at 425 nm. Furthermore, the NRG-SNPs were analyzed for size, PDI, and zeta potential, which were found to be 35 ± 0.21 nm, 0.19 ± 0.03, and 17.73 ± 0.92 mV, respectively. In silico results demonstrated that NRG had a strong affinity towards the sterol 14α-demethylase. The docking with ceramide revealed the skin permeation efficiency of the NRG-SNPs. Next, the NRG-SNPs were loaded into the topical dermal dosage form (NRG-SNPs-TDDF) by formulating a gel using Carbopol Ultrez 10 NF. The MIC50 of NRG solution and TSC-SNPs against C. albicans was found to be 50 µg/mL and 4.8 µg/mL, respectively, significantly (P < 0.05) higher than 0.3625 µg/mL of NRG-SNPs-TDDF. Correspondingly, MIC50 results were calculated against C. glabrata and the results of NRG, TSC-SNPs, NRG-SNPs-TDDF, and miconazole nitrate were found to be 50 µg/mL, 9.6 µg/mL, 0.3625 µg/mL, and 3-µg/mL, respectively. Interestingly, MIC50 of NRG-SNPs-TDDF was significantly (P < 0.05) lower than MIC50 of miconazole nitrate against C. glabrata. The FICI (fractional inhibitory concentration index) value against both the C. albicans and C. glabrata was found to be 0.016 and 0.011, respectively, which indicated the synergistic antifungal activity of NRG-SNPs-TDDF. Thus, NRG-SNPs-TDDF warrants further in depth in vivo study under a set of stringent parameters for translating in to a clinically viable antifungal product.

Congenital cutaneous candidiasis in a full-term neonate.

We present a case of a full-term neonate born with respiratory distress and a widespread erythematous rash, who was found to have congenital cutaneous candidiasis (CCC). The significance of this report is to contribute to the pre-existing literature on the rarity of CCC, but also to share a case of a patient who was successfully treated conservatively with topical antifungal agents only.

Onychodystrophy as the only sign of congenital candidiasis.

Congenital candidiasis infection often presents as a skin rash with variable involvement of nails and mucous membranes. Isolated nail involvement is rare, may present late, and can often be managed with topical antifungal medication. We report a case of congenital candidiasis limited to the fingernails that resolved completely within 3 months with topical treatment.

Cutaneous candidiasis - an evidence-based review of topical and systemic treatments to inform clinical practice.

Cutaneous candidiasis is a common skin disease, and several treatments have been investigated within the last fifty years. Yet, systematic reviews are lacking, and evidence-based topical and systemic treatment strategies remain unclear. Thus, the aim of this review was to summarize efficacy and adverse effects of topical and oral therapies for cutaneous candidiasis in all age groups. Two individual researchers searched PubMed and EMBASE for 'cutaneous candidiasis' and 'cutaneous candidiasis treatment', 'intertrigo', 'diaper dermatitis' and 'cheilitis'. Searches were limited to 'English language', 'clinical trials' and 'human subjects', and prospective clinical trials published in abstracts or articles were included. In total, 149 studies were identified, of which 44 were eligible, comprising 41 studies of 19 topical therapies and four studies of three systemic therapies for cutaneous candidiasis. Topical therapies were investigated in infants, children, adolescents, adults and elderly, while studies of systemic therapies were limited to adolescents and adults. Clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated similar efficacy with complete cure rates of 73%-100%. Single-drug therapy was as effective as combinations of antifungal, antibacterial and topical corticosteroid. Four studies investigated systemic therapy, and oral fluconazole demonstrated similar efficacy to oral ketoconazole and topical clotrimazole. Limitations to this review were mainly that heterogeneity of studies hindered meta-analyses. In conclusions, clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated equal good efficacy and mild adverse effects similar to combinations of antifungal, antibacterial and topical corticosteroids. Oral fluconazole was as effective as topical clotrimazole and is the only commercially available evidence-based option for systemic treatment of cutaneous candidiasis.

Impact of Process Parameters on Particle Size Involved in Media Milling Technique Used for Preparing Clotrimazole Nanocrystals for the Management of Cutaneous Candidiasis.

Clotrimazole is widely used for the management of cutaneous candidiasis infection. The low solubility of clotrimazole and excipient-related topical side effects (of currently available marketed products) cause the compromised efficacy of the therapy with poor patient compliance. In the present investigation, a clotrimazole nanocrystal-based nanogel was developed. Clotrimazole nanocrystals were optimized with studying the impact of individual process parameters of the media milling technique. The optimum level of individual process parameters was considered in the development of optimized batches. A promising result was obtained with a non-ionic stabilizer, polysorbate 80, at a concentration of 1.5%w/v, showing a distinct reduction in the particle size from above 31 µm to 264 nm and a polydispersity index of 0.211 with media milling at 1500 rpm for 6 h. This result was found to be in concordance with the TEM images, revealing a sharp diminution in particle morphology. Powder X-ray diffraction and differential scanning calorimetry results revealed crystallinity of clotrimazole (CTZ) in nanocrystal form. The optimized nanocrystal suspension was formulated into nanogel with carbopol 934, having a viscosity of 86.43 ± 2.06 Pa s at 25°C, which enhanced the ease of application of CTZ nanocrystals topically. A diffusion study showed around 82% of CTZ is transported across the membrane with the flux of 110.07 µg cm-2 h-1. In vivo results of the nanogel revealed improvement in CTZ release with 52% CTZ retention in different strata of the skin. The developed nanogel showed a significant improvement in the eradication of fungal infection within 10 days of application over Candida albicans-induced Wistar rat model. In a nutshell, the CTZ nanocrystal-loaded nanogel could achieve the goal of retaining CTZ in skin layers providing a prolonged effect and was able to treat cutaneous candidiasis in a short span with improved compliance for the candidiasis patients.

Two Cases of Chronic Candidiasis in Keratitis-Ichthyosis-Deafness Syndrome.

Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis that typically results from mutations of the GJB2 gene or, less commonly, the GJB6 gene. Patients with KID syndrome are at higher risk of malignancy and infections. Here, we present 2 patients with KID syndrome who developed verrucous plaques. Given that patients with KID syndrome are at high risk of developing squamous cell carcinoma, biopsies were performed. Both cases revealed histologic findings of marked papillomatous epidermal hyperplasia with numerous fungal spores and pseudohyphae in the stratum corneum. For one case, daily oral fluconazole was initiated. The patient demonstrated dramatic resolution of his foot plaques over the course of 2 years. These cases highlight that, for the dermatopathologist, chronic fungal infection should be sought for verrucous plaques in patients with KID syndrome as, if present, this finding may alter treatment and quality of life.

Erosio interdigitalis blastomycetica: A review of interdigital candidiasis.

Erosio interdigitalis blastomycetica (EIB) is a Candida infection affecting the third web space, between the third and fourth fingers. In 1915, Gougerot and Goncea first described saccharomycetic organisms isolated from the hands and feet. Johannes Fabry later named it in 1917, well before the genus Candida was introduced in 1923. EIB is most common among those who work with their hands frequently in water, such as dishwashers, launderers, bartenders, and homemakers. Clinical presentation most commonly consists of a central erythematous erosion surrounded by a rim of white macerated skin involving at least one interdigital web space. The differential diagnosis is narrow, consisting of irritant contact dermatitis (ICD), erythrasma, inverse psoriasis, and bacterial infection (i.e. impetigo). The diagnosis is made by clinical examination in addition to fungal culture and KOH testing. The prognosis is good and treatment options include avoidance of frequent water immersion and topical or oral antifungal agents. Suspicion for secondary infections such as erysipelas and cellulitis should remain high until lesions have resolved. This review aims to address the history, epidemiology, pathophysiology, histopathology, clinical presentation, differential diagnoses, diagnosis, prognosis, and management of EIB. It also suggests an alternative name in place of the current misnomer.

Congenital Cutaneous Candidiasis: Prompt Systemic Treatment Is Associated With Improved Outcomes in Neonates.

BACKGROUND: Congenital cutaneous candidiasis (CCC) is a challenging diagnosis due to various rash presentations. Inadequate early treatment is associated with high rates of dissemination and death. The effects of early diagnosis, dermatologic presentation, and antifungal treatment on outcomes are lacking. METHODS: CCC cases were reviewed from 2 academic neonatal intensive care units (NICUs) from 2004 to 2015. We defined CCC as a diffuse rash involving the body, extremities, face or scalp, and/or funisitis, presenting in the first week (≤7 days), with identification of Candida species from skin or mucous membrane cultures, and/or by culture or staining of the placenta or umbilical cord. RESULTS: CCC occurred in 0.1% of all NICU admissions (21 of 19 303) and 0.6% of infants <1000 grams birth weight. Median gestational age of CCC infants was 26 3/7 (range, 23 0/7-40 4/7) weeks. Skin findings were commonly present on the day of birth [median (range): 0 (0-6) days], appearing most frequently as a desquamating, maculopapular, papulopustular, and/or erythematous diffuse rash. When systemic antifungal therapy was started empirically at the time of rash presentation and continued for a median (interquartile range) of 14 (14-15) days, all patients survived and none developed dissemination. Delaying systemic treatment, exclusive use of nystatin, and treating for <10 days was associated with Candida bloodstream dissemination. CONCLUSIONS: CCC is an invasive infection that presents as a diffuse rash in preterm and term infants. Prompt systemic antifungal treatment at the time of skin presentation for ≥14 days prevents dissemination and Candida-related mortality.

Cutaneous Candidiasis in a Gottingen Minipig: A Potential Pitfall in Preclinical Studies.

The Göttingen minipig is often used in preclinical toxicity studies. Therefore, knowledge of spontaneously occurring pathologies is important to differentiate them from test drug-related effects. We report on a Göttingen minipig, which developed exudating widespread dermatitis during a preclinical toxicity study with a subcutaneously injected drug. The lesions were resistant to topical and oral antibacterial medications. Skin cultures were positive for Candida albicans, and treatment was changed to topical antifungal cream with quick resolution of the skin lesions. Cutaneous candidiasis in pigs has been rarely reported in the literature, and this is the first report on such condition in preclinical toxicity studies. Knowledge of this condition, which is not drug related, is important, especially in toxicity studies involving subcutaneous injections that are commonly accompanied by inflammatory skin reactions.

Fournier Gangrene Caused by Candida albicans in an Infant After Cardiac Surgery.

Fournier gangrene is a rare, rapidly progressive, life-threatening condition. We report a 23-day-old boy with pulmonary atresia and ventricular septal defect treated surgically, who developed Fournier gangrene. Emergency surgery was performed with tissue sampling for microbiological examination. Candida albicans was confirmed; caspofungin followed by fluconazole was administered with excellent results.

Successful treatment of recalcitrant candidal intertrigo with Dr Michaels® (Fungatinex®) product family.

Candidal intertrigo is an infection of the skin caused by Candida albicans that typically occurs in opposing cutaneous or muco-cutaneous surfaces. Because Candidiasis requires a damaged and moist environment for infection, it typically occurs in areas of friction such as the skin folds of the body. Candidal intertrigo is often difficult to treat and results are often unsatisfactory. In addition, there is a lack of evidence-based literature supporting prevention and treatments for candidal intertrigo. The aim of the study was to evaluate the efficacy of Dr Michaels® (also branded as Fungatinex®) products in the treatment of fungal intertrigo, in 20 women and 2 men with a mean age of 72. Five patients (3 female and 2 male) had type 2 diabetes and 16 (14 female and 2 male) were obese. The patients were treated with Dr Michaels® (Fungatinex®) moisturising bar, topical ointment (twice daily application) and oral herbal formulation, PSC 200 two tablets twice daily with food. After 2 weeks of treatment, the lesions had mostly resolved in all patients with only slight erythema evident. After six weeks of treatment using the moisturising bar, topical ointment and oral herbal formulations from the Dr Michaels® (Fungatinex®) product family, the lesions had totally resolved in 18 patients, while 4 patients had to continue the therapeutic protocol for another 2 weeks. Our results demonstrate that the Dr Michaels® (Fungatinex®) complementary product family is efficacious in the treatment of recalcitrant candidal intertrigo. Furthermore, this study highlights that the Dr Michaels® (Fungatinex®) product family is fast-acting and well tolerated with no serious adverse events reported. These data have important implications for resistant cases of candidal intertrigo where traditional therapies have failed.

Primary deep cutaneous candidiasis caused by Candida duobushaemulonii in a 68-year-old man: the first case report and literature review.

Superficial candida infections of the skin are common, but deep cutaneous candidiasis, including secondary dissemination to the skin from systemic candidiasis, candidaemia or primary invasion due to skin defects such as trauma, is rare. These patients are usually immunosuppressed, but immunocompetent hosts can be affected as well. Candida albicans is the most common pathogen. However, non-albicans Candida species can cause deep skin invasion in rare circumstances. We report a case of deep cutaneous candidiasis caused by Candida duobushaemulonii in a 68-year-old man. Deep tissue invasion was confirmed by skin histopathology examination. The pathogen was initially identified as C. haemulonii using the VITEK® 2 system for microbial identification, but was later determined to be C. duobushaemulonii based on sequencing of the internal transcribed spacer region of ribosomal DNA and D1/D2 region of 26S rDNA. The patient was successfully treated with amphotericin B, followed by fluconazole and surgical intervention. To the best of our knowledge, this is the first case of deep cutaneous infection by C. duobushaemulonii.

Thiamine antivitamins--an opportunity of therapy of fungal infections caused by Malassezia pachydermatis and Candida albicans.

Severe skin diseases and systemic fungaemia are caused by Malassezia pachydermatis and Candida albicans respectively. Antifungal therapies are less effective because of chronic character of infections and high percentage of relapses. Therefore, there is a great need to develop new strategies of antifungal therapies. We previously found that oxythiamine decreases proliferation of yeast (Saccharomyces cerevisiae), therefore we suggest that thiamine antivitamins can be considered as antifungal agents. The aim of this study was the comparison of thiamine antivitamins (oxythiamine, amprolium, thiochrome, tetrahydrothiamine and tetrahydrooxythiamine) inhibitory effect on the growth rate and energetic metabolism efficiency in non-pathogenic S. cerevisiae and two potentially pathogenic species M. pachydermatis and C. albicans. Investigated species were cultured on a Sabouraud medium supplemented with trace elements in the presence (40 mg l(-1)) or absence of each tested antivitamins to estimate their influence on growth rate, enzyme activity and kinetic parameters of pyruvate decarboxylase and malate dehydrogenase of each tested species. Oxythiamine was the only antivitamin with antifungal potential. M. pachydermatis and S. cerevisiae were the most sensitive, whereas C. albicans was the least sensitive to oxythiamine action. Oxythiamine can be considered as supportive agent in superficial mycoses treatment, especially those caused by species from the genus Malassezia.

Mycological Considerations in the Topical Treatment of Superficial Fungal Infections.

Trichophyton rubrum remains the most common pathogenic dermatophyte in the United States, Europe, and industrialized Asia, although other species are predminant elsewhere. Candida albicans is the most common pathogenic yeast, with other species occasionally encountered. Just a few of the 14 described species of Malassezia cause pityriasis versicolor worldwide. FDA approval does not always accurately reflect the potential utility of any given topical antifungal agent. Azole, hydroxypyridone, and allylamine agents are beneficial in the management of dermatophytosis; however, the allylamines may lead to faster symptom resolution and a higher degree of sustained response. Although in actual clinical use the allylamines have all shown some activity against superficial cutaneous candidiasis and pityriasis versicolor, the azole agents remain drugs of choice. Ciclopirox is an excellent broad-spectrum antifungal agent. Optimal topical therapy for superficial fungal infections cannot yet be reliably based upon in-vitro laboratory determination of sensitivity. Inherent antibacterial and anti-inflammatory properties possessed by some antifungal agents may be exploited for clinical purposes. Candida species may be azole-insensitive due to efflux pumps or an altered target enzyme. So-called "antifungal resistance" of dermatophyets is actually due to poor patient adherence (either in dosing or treatment duration), or to reinfection.

Efficacy and Safety in 1% Clotrimazole Powder, Adjuvant Therapy in Patients with Superficial Fungal Cutaneous Infection in Intertriginous Areas.

Background: Superficial fungal cutaneous infection is commonly found in intertriginous area. Objective: To assess 1% clotrimazole powder (1% CP) efficacy for adjuvant treatment of superficial fungal cutaneous infection in intertriginous areas. Material and Method: The study performed as an open-label, randomized, comparative study for evaluating the effects of 1% clotrimazole cream (1% CC) with 1% CP in patients infected with dermatophytes (DMPs) or Candida spp. in intertriginous area, comparing to patients treated with 1% CC as control by demonstrating complete cure rate at 4, 8, and 12 weeks as well as relapse rates during a 24-week period including patient satisfaction. Results: Sixty-seven patients with mean age of 54.6 years were included in this study. Of those, 61.2% were males. Thirty-five patients were infected with DMPs and 32 with Candida spp. The complete cure rates of experimental group were significantly higher than the control group, as observed within four weeks (p = 0.01), especially for dermatophyte infection (p = 0.039). Two cases had recurrent candidiasis in the control group. In both groups, relapse up to 24 weeks were not statistically different. Additionally, there was no difference in patients' satisfaction towards convenience of drug application. Conclusion: Using of the 1% CP could be suggested as an adjuvant therapy and possibly preventive agent for superficial fungal cutaneous infection in intertriginous areas.

Folliculocentric cutaneous presentation of disseminated Candida krusei infection in a patient with acute myeloid leukemia.

Candida krusei (C. krusei) is a multidrug-resistant opportunistic fungal pathogen that may cause disseminated infections in immunocompromised hosts. However, its clinical and histologic features are not well-characterized. We present a unique case to contribute to the growing knowledge base associated with this organism. During hospitalization for neutropenic fever, a 19-year-old man with acute myeloid leukemia, who underwent hematopoietic stem cell transplantation, developed a generalized folliculocentric eruption following initiation of antifungal therapy for newly diagnosed C. krusei fungemia. Despite adequate antifungal coverage and negative blood cultures, the follicular-based erythematous papules persisted. Biopsies demonstrated yeast within ruptured follicles, without angiotropism or involvement of the interfollicular dermis, subcutaneous tissue, or stratum corneum. Concurrent skin tissue cultures confirmed C. krusei. The patient remained febrile despite aggressive antifungal therapy, with relapse of leukemia and subsequent death. Our case is unusual given the development of cutaneous lesions following clearance of fungemia, with yeast limited to ruptured follicular lumina, possibly indicating a primary cutaneous source or early transfollicular/transepidermal elimination. Given the limited available descriptions of cutaneous histopathology for C. krusei, we seek to add to the understanding of its pathophysiology and aid in the diagnosis and treatment of this often fatal infection.

Oral administration of the broad-spectrum antibiofilm compound toremifene inhibits Candida albicans and Staphylococcus aureus biofilm formation in vivo.

We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

Clinical and cytologic features of antibiotic-resistant acute paronychia.

BACKGROUND: Acute paronychia usually is treated as a bacterial infection, but antibiotic-resistant acute paronychia may be caused by other infectious and noninfectious problems. OBJECTIVE: We sought to describe the clinical, etiologic, cytologic, and therapeutic features of antibiotic-resistant acute paronychia. METHODS: A retrospective review of medical records and cytology was performed in 58 patients (age, 1 month-91 years; 36 children and adolescents [62%] and 22 adults [38%]) who had antibiotic-resistant acute paronychias. RESULTS: Causes of paronychia included bacteria (25 patients [43%]), viruses (21 patients [36%]), fungi (5 patients [9%]), drugs (3 patients [5%]), pemphigus vulgaris (3 patients [5%]), and trauma (1 patient [2%]). Diagnostic cytologic findings were noted in 54 patients (93%); no diagnostic cytologic findings were present with drug-induced (3 patients) or traumatic (1 patient) paronychia. The most common predisposing factors were the habits of finger- or thumb-sucking (14 patients [24%]) and nail-biting (11 patients [19%]). Complications included id reaction with erythema multiforme in 3 patients (5%). LIMITATIONS: Limitations include retrospective study design from 1 treatment center. CONCLUSION: Antibiotic-resistant acute paronychia may be infectious or noninfectious. Cytologic examination with Tzanck smear may be useful diagnostically and may prevent unnecessary use of antibiotics and surgical drainage.