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.

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.

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.

Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r.

Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50µg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400µg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections.

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.

[Clinical problems in medical mycology: Problem number 48]. / Problemas clínicos en micología médica: problema número 48.

We present the case of a 42-year-old man, HIV-positive, with low CD4(+) T cell count (31 cells/µl), who was admitted to Hospital de Infecciosas F. J. Muñiz in Buenos Aires (Argentina) due to a severe lower back pain. He had a history of several highly active antiretroviral therapy treatments and he also had diabetes and chronic B and C viral hepatitis. A spinal cord CT scan showed two lytic bone lesions in L2 and L3. A bone biopsy was carried out and its microbiological study allowed the isolation of a methicillin-resistant Staphylococcus aureus. Intravenous vancomycin was prescribed, together with a corset and physical rest. A few days later the patient presented with acute dermatitis with papules, vesicles, scales and erythema, which spread over the whole lumbar region. The mycological study of the scales led to the isolation in culture of Candida albicans and Candida parapsilosis. With the diagnosis of decubitus candidiasis he was initially treated with a topical ointment containing 3% salicylic acid and 6% benzoic acid, but only slow, partial improvement was observed. The treatment was changed to oral fluconazole at a daily dose of 200mg. With the latter the patient showed a rapid, complete clinical response.

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.

[Finger onychomycosis due to Candida tropicalis: short-pulsed Nd:YAG laser therapy]. / Traitement d'une onychomycose digitale à Candida tropicalis par laser Nd:Yag Short Pulse.

BACKGROUND: Treatment options for onychomycosis are numerous but of limited efficacy, potentially dangerous and/or relatively restrictive. PATIENTS AND METHODS: We describe the first case of Candida tropicalis onychomycosis resistant to standard topical treatments successfully treated with four sessions of Nd:YAG laser in Short Pulse mode. The efficacy of treatment was verified at 3 months via a negative control sample and was maintained for at least 6 months. DISCUSSION: Nd:YAG laser is a versatile type of laser widely used in dermatology. Its mode of action in the treatment of onychomycosis may consist of a thermal effect that is non-specific but differentiates between healthy nail and diseased nail, which respond differently to impact. The main interest of this case is in helping to pave the way for a new type of treatment for onychomycosis.

Cutaneous candidiasis caused by Candida glabrata in a HIV/AIDS patient.

Cutaneous Candida infections may occur in patients with HIV/AIDS, cancer, receiving chemotherapy and solid organ transplantation. A 32-year-old woman was admitted to the department suffering from pruritic and erythematous plaque on left side of her face for the past two months. The patient was HIV positive, diagnosed five years previously, and had been on antiretroviral therapy (tenofovir/emtricitabine and lopinavir/ritonavir) for a year. She was not compliant with the medication. Elevated HIV RNA load and decreased CD4+ lymphocyte count were observed. Fungal elements were detected from the skin scraping sample taken from the facial plaque. Fluconazole-sensitive Candida glabrata was isolated from this sample. Topical clotrimazole ointment and systemic fluconazole 400 mg/day were used. After systemic fluconazole therapy was continued for two months, the plaque was cured. C. glabrata rarely causes cutaneous infection without involving the mucous membranes. Presentation of cutaneous fungal infections in HIV patients with decreased CD4+ T lymphocyte counts can be atypical and require extensive antifungal treatment.

Potentiation of azole antifungals by 2-adamantanamine.

Azoles are among the most successful classes of antifungals. They act by inhibiting α-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of Candida albicans. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of C. albicans but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar. In vivo, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (P value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics.

[Generalized cutaneous candidiasis in newborn at term]. / Candidiasis cutánea generalizada en recién nacido a término.

INTRODUCTION: Cutaneous candidiasis is a disease that affects children as well as adults. The presentation may be localized or systemic, and with multiple etiological agents. The most prevalent infecting species in children differs from that of the adult. OBJECTIVE: A case is presented where a congenital cutaneous candidiasis was transmitted to the child during birth. MATERIALS AND METHODS: A full term newborn was exposed to a subclinical vaginal candidiasis infection, and 24 hr after birth, developed congenital cutaneous candidiasis. The etiological agent was Candida albicans, and was associated with sepsis and respiratory distress. Blood cultures, cutaneous biopsy of vesicular lesions, blood tests and lumbar puncture were performed. RESULTS: Biochemistry and blood count showed a CRP of 5.7 mg/dl, leukocytosis with left shift and mild anemia. After 24 hr, the blood analyses showed an increase in a CRP (7.8 mg/dl) and increased progressively for three days; consequently, a lumbar puncture was performed. Blood culture was positive for Staphylococcus aureus. Cutaneous biopsy confirmed the cutaneous candidiasis. CONCLUSIONS: The early diagnosis is essential to prevent complications derived by the Candida albicans in newborns.

Candidiasis cutánea generalizada en recién nacido a término / Generalized cutaneous candidiasis in newborn at term

Introducción. La candidiasis cutánea es una enfermedad que afecta tanto a población infantil como adulta. Las forma de presentación puede ser localizada o sistémica y el agente etiológico múltiple, siendo las especies infecciosas de Candida albicans más prevalentes en niños. Objetivo. Presentar un caso de candidiasis cutánea congénita cuya causa aparente fue la transmisión vertical durante el parto. Material y metodología. Se describe el caso de un recién nacido a término expuesto a una candidiasis vaginal subclínica, que desarrolló una candidiasis cutánea congénita por C. albicans asociada a sepsis y dificultad respiratoria en las primeras 24 horas de vida. Se practicaron hemocultivos, biopsia cutánea de las lesiones pápulopústulo-vesiculosas, análisis de sangre y punción lumbar. Resultados. En la bioquímica y el hemograma se encontró una proteína C reactiva de 5,7 mg/dl, leucocitosis con desviación a la izquierda y anemia leve. A las 24 horas, en el control se encontró una proteína C reactiva (7,82 mg/dl) que fue en aumento progresivo durante tres días, por lo que se practicó punción lumbar. El hemocultivo fue positivo para Staphylococcus aureus. La biopsia cutánea dio como resultado histológico la candidiasis cutánea. Conclusiones. El diagnóstico precoz es fundamental para prevenir complicaciones derivadas del cuadro producido por C. albicans en neonatos.

Introduction. Cutaneous candidiasis is a disease that affects children as well as adults. The presentation may be localized or systemic, and with multiple etiological agents. The most prevalent infecting species in children differs from that of the adult. Objective. A case is presented where a congenital cutaneous candidiasis was transmitted to the child during birth. Materials and methods. A full term newborn was exposed to a subclinical vaginal candidiasis infection, and 24 hr after birth, developed congenital cutaneous candidiasis. The etiological agent was Candida albicans, and was associated with sepsis and respiratory distress. Blood cultures, cutaneous biopsy of vesicular lesions, blood tests and lumbar puncture were performed. Results. Biochemistry and blood count showed a CRP of 5.7 mg/dl, leukocytosis with left shift and mild anemia. After 24 hr, the blood analyses showed an increase in a CRP (7.8 mg/dl) and increased progressively for three days; consequently, a lumbar puncture was performed. Blood culture was positive for Staphylococcus aureus. Cutaneous biopsy confirmed the cutaneous candidiasis. Conclusions. The early diagnosis is essential to prevent complications derived by the Candida albicans in newborns.

Eficácia de antifúngicos tópicos em diferentes dermatomicoses: uma revisão sistemática com metanálise / Efficacy of topical antifungal drugs in different dermatomycoses: a systematic review with meta-analysis

OBJETIVO: Avaliar e comparar a eficácia dos antifúngicos tópicos empregados no tratamento de cada dermatomicose. MÉTODOS: Foi desenvolvida uma revisão sistemática de ensaios clínicos randomizados, publicados em português, espanhol ou inglês até julho de 2010, que comparassem o uso de antifúngicos azólicos e alilamínicos entre si ou com placebo, no tratamento de candidíase cutânea, e das tineas versicolor, pedis, cruris e corporis. Os desfechos de eficácia avaliados foram cura micológica ao final do tratamento e cura sustentada. RESULTADOS: Dos 4.424 estudos inicialmente identificados, 49 alcançaram os critérios de seleção, sendo incluídos nas metanálises. Os dados agrupados de eficácia demonstraram superioridade dos antifúngicos frente a placebo, independente da dermatomicose avaliada, com valores de odds ratio (OR) variando de 2,05 (IC 95% 1,18-3,54) a 67,53 (IC 95% 11,43-398,86). Alilaminas foram superiores aos azólicos apenas para o desfecho cura sustentada (OR 0,52 [IC 95% 0,31-0,89]). CONCLUSÃO: Há evidência consistente da superioridade dos antifúngicos com relação ao uso de placebo, não sendo mais justificável a realização de estudos controlados por placebo. Alilaminas mantêm a cura micológica por períodos mais extensos que fármacos azólicos. Dada a significativa diferença de custo entre as classes, recomenda-se a realização de análises farmacoeconômicas.

OBJECTIVE: To evaluate and compare the efficacy of topical antifungal drugs applied to the treatment of each dermatomycosis. METHODS: A systematic review of randomized clinical trials, published in Portuguese, Spanish and English until July 2010, which compared the use of azole and allylamine antifungal drugs among themselves and with placebo in the treatment of cutaneous candidiasis and T. versicolor, T. pedis, T. cruris and T. corporis was performed. The efficacy outcomes evaluated were mycological cure at the end of treatment and sustained cure. RESULTS: Of the 4,424 studies initially identified, 49 met the selection criteria and were included in the meta-analyses. The grouped efficacy data evidenced the superiority of antifungal drugs compared to placebo, regardless of the dermatomycosis under evaluation, with odds ratio values ranging from 2.05 (95% CI 1.18-3.54) to 67.53 (95% CI 11.43-398.86). Allylamines were better than azoles only for the outcome sustained cure (OR 0.52 [95% CI 0.31-0.89]). CONCLUSION: There is consistent evidence of the superiority of antifungal drugs over the use of placebo, and placebo-controlled studies are no longer justifiable. Allylamines maintain the mycological cure for longer periods compared to azole drugs. Given the significant cost difference among the classes, pharmacoeconomic analyses should be performed.