A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection.

Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of Cryptococcus neoformans and Candida albicans infection in combination with fluconazole-a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with C. neoformans and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 ± 0.289 log10 reduction) and lung (mean 1.72 ± 0.399 log10 reduction) compared to fluconazole treatment on a conventional diet. During C. albicans infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 ± 0.770 log10-reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both C. neoformans and C. albicans infection and could have practical and promising treatment implications.IMPORTANCEInvasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both C. neoformans and C. albicans in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.

The dietary modification and treatment of intestinal Candida overgrowth - a pilot study.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of an alternative treatment in a form of recommended diet modification during and after conventional treatment with antifungals in patients with a chronic form of intestinal Candida overgrowth (ICOG). METHODS: The study included patients with ICOG divided in two subgroups: patients treated with nystatin and recommended diet regime (study group-SG) and the patients treated only with nystatin (control group-CG). After treatment, the mycological control examination and follow-up were performed two times: the first one within ten days after the completion of antifungal treatment, and the second one three months after the treatment initialization. RESULTS: A total of 120 patients finished the study: 80 from the SG and 40 from the CG. At the first mycological control examination of SG patients stools, we noted satisfactory antifungal and symptomatic effect in 56 out of 80 (70.0%) patients and 29 out of 40 (72.5%) in CG, with no statistically significant difference. However, at the second control stool examination, significantly higher percent (85%) of cured patients was recorded after three months of the recommended diet comparing with CG-17 out of 40 (42.5%). CONCLUSION: Results of this pilot study showed that patients who adhered to diet modification during and after treatment with nystatin had better outcomes of ICOG and strongly suggest the need for diet modification in these patients which recommendation could reduce excessive prescription of antifungals.

Investigation and simulation of dissolution with concurrent degradation under healthy and hypoalbuminaemic simulated parenteral conditions- case example Amphotericin B.

Guidance on dissolution testing for parenteral formulations is limited and not often related in vivo performance. Critically ill patients represent a target cohort, frequently hypoalbuminaemic, to whom certain parenteral formulations are administered. Amphotericin B (AmB) is a poorly soluble, highly protein-bound drug, available as lipid-based formulations and used in critical illness. The aim of this study was to develop media representing hypoalbuminaemic and healthy plasma, and to understand and simulate the dissolution profile of AmB in biorelevant media. Dissolution media were prepared with bovine serum albumin (BSA) in Krebs-Ringer buffer, and tested in a flow through cell apparatus and a bottle/stirrer setup. Drug activity was tested against Candida albicans. BSA concentration was positively associated with solubility, degradation rate and maximum amount dissolved and negatively associated with dissolution rate constant and antifungal activity. In the bottle/stirrer setup, a biexponential model successfully described simultaneous dissolution and degradation and increased in agitation reduced the discriminatory ability of the test. The hydrodynamics provided by the flow-through cell apparatus was not adequate to dissolve the drug. Establishing discriminating test methods with albumin present in the dissolution media, representing the target population, supports future development of biorelevant and clinically relevant tests for parenteral formulations.

Population Pharmacokinetic Analyses for Rezafungin (CD101) Efficacy Using Phase 1 Data.

Rezafungin (CD101) is a novel echinocandin antifungal agent currently in clinical development for the treatment of candidemia and invasive candidiasis. Rezafungin has potent in vitro activity against Candida albicans and Candida glabrata, including azole- and echinocandin-resistant isolates. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the disposition of rezafungin in plasma following intravenous (i.v.) administration. Data from two phase 1 studies, a single-ascending-dose study and a multiple-ascending-dose study, were available. Candidate population PK models were fit to the pooled data using the Monte Carlo parametric expectation maximization algorithm in S-ADAPT. The data were best described using a linear four-compartment model with zero-order drug input via i.v. infusion and first-order elimination. In order to account for the relationships between the structural PK parameters and subject body weight, all parameters in the model were scaled to subject body weight using standard allometric coefficients (a power of 0.75 for the clearance terms and 1.0 for the volume terms). The final model fit the observed data with very little bias and excellent precision. The prediction-corrected visual predictive check demonstrated that the final model could accurately simulate both the central tendency and the variability of observed rezafungin plasma concentrations. Given this, the final rezafungin population PK model is expected to provide reliable simulated concentration-time profiles and can provide dose selection decision support for future clinical studies.

Probiotics for vaginal health in South Africa: what is on retailers' shelves?

BACKGROUND: Probiotics are widely used to improve gastrointestinal (GI) health, but they may also be useful to prevent or treat gynaecological disorders, including bacterial vaginosis (BV) and candidiasis. BV prevalence is high in South Africa and is associated with increased HIV risk and pregnancy complications. We aimed to assess the availability of probiotics for vaginal health in retail stores (pharmacies, supermarkets and health stores) in two major cities in South Africa. METHODS: A two-stage cluster sampling strategy was used in the Durban and Cape Town metropoles. Instructions for use, microbial composition, dose, storage and manufacturers' details were recorded. RESULTS: A total of 104 unique probiotics were identified in Cape Town and Durban (66.4% manufactured locally). Cape Town had more products than Durban (94 versus 59 probiotics), although 47% were common between cities (49/104). Only four products were explicitly for vaginal health. The remainder were for GI health in adults (51.0%) or infants (17.3%). The predominant species seen overall included Lactobacillus acidophilus (53.5%), L. rhamnosus (37.6%), Bifidobacterium longum ssp. longum (35.6%) and B. animalis ssp. lactis (33.7%). Products for vaginal health contained only common GI probiotic species, with a combination of L. acidophilus/B. longum ssp. longum/B. bifidum, L. rhamnosus/L. reuteri or L. rhamnosus alone, despite L. crispatus, L. gasseri, and L. jensenii being the most common commensals found in the lower female reproductive tract. CONCLUSION: This survey highlights the paucity of vaginal probiotics available in South Africa, where vaginal dysbiosis is common. Most vaginal products contained organisms other than female genital tract commensals.

Invasive Candida krusei infection and Candida vasculitis of a leg ulcer in an immunocompetent patient: A case report.

A 71year old female Caucasian farmer without any known immunosuppression presented with a painful ulcer of her right lower leg after a trauma caused by a wood billet. There was no response to empirical antibacterial treatment. An ulcer biopsy showed an invasive Candida infection of the soft tissue and leucocytoclastic vasculitis. Voriconazole treatment was followed by wound healing. Invasive Candida infection and localized Candida vasculitis represent a rare cause of persisting leg ulcers. The similar clinical picture of chronic venous leg ulcers might blur the true cause and refractory cases should therefore promptly be processed by histopathological diagnostics.

Papel de los probióticos en Obstetricia y Ginecología / Role of probiotics in obstetrics and gynecology

La microbiota de cada individuo se estima en 2,5-3 kg de peso. La colonización bacteriana comienza en el momento del parto, por contacto del feto con la microbiota vaginal e intestinal de la madre. Los oligosacáridos de la leche materna estimulan el crecimiento de bacterias, que proporcionan el ambiente adecuado para el desarrollo de la inmunidad de la mucosa intestinal. Además, la leche materna es portadora de su propia microbiota, la cual se altera en las mastitis. La vagina constituye otro importante microambiente. Las disbiosis en esta zona conducen a la aparición de vaginosis bacteriana y candidiasis, siendo ambas una patología muy frecuente en la mujer en edad fértil. Los probióticos se presentan como tratamiento potencial y alentador de toda la patología asociada a alteraciones de la microbiota. Son necesarios más estudios que confirmen el beneficio de los probióticos en este campo (AU)

The human microbiota is estimated to be 2.5-3.0 kg. Bacterial colonization starts during delivery, due to fetal contact with vaginal and intestinal maternal microorganisms. The oligosaccharides in human breast milk stimulate the growth of bacteria, which provide the optimal environment for intestinal mucosal immunity development. Additionally, breast milk has its own microbiota and it is altered in mastitis. The vagina is another important microenvironment. Vaginal dysbiosis leads to bacterial vaginosis and vaginal candidiasis, both of them very frequent in reproductive life. The probiotics are a potential and encouraging treatment for all microbiota alterations. Nevertheless, additional studies are required to confirm the benefits of probiotics (AU)

[Dietetic-therapeutic intervention in Candidiasis intestinal]. / Intervención dietético-terapéutica en Candidiasis intestinal.

BACKGROUND: Candidiasis are opportunistic yeast infections, the most common etiologic agent involved C.albicans creating problems at various levels. CASE REPORT: 39-year old woman diagnosed by chronic intestinal Candidiasis studying with wide and varied symptoms. After evaluation proceeds to complement treatment with diet consisted in removal of simple sugars, yeast and fermented products. Furthermore, caprylic acid and oregano oil L.acidophylus include. CONCLUSIONS: There is an increased immunological activity accompanied by symptomatic improvement.

Antecedentes: Las candidiasis son infecciones oportunistas producidas por levaduras, cuyo agente etiológico implicado más frecuente C.albicans generando problemas a varios niveles. Caso clínico: Mujer de 39 años diagnosticada de Candidiasis intestinal crónica cursando con sintomatología amplia y variada. Tras la valoración se procede a complementar el tratamiento con una alimentación centrada en la eliminación de azúcares simples, levaduras y productos fermentados. Además, se incluyen ácido caprílico, aceite de orégano y L.acidophylus. Conclusiones: Existe un aumento de la actividad inmunológica acompañada de la mejora sintomatológica.

[Peculiarities of diet therapy in children with duodenal ulcers associated with the genus Candida].

In children with relapsing DU in 50.8% cases there is a complicated disease course with Candida infection, as evidenced by the positive results of mycological examination of biopsy specimens of duodenal mucosa and detection of circulating Candida antigen in serum. The use in the complex therapy in children with DU associated with Candida species of instant New Zealand goat milk "Amalteya" leads to an overall therapeutic effect in 81.3% cases, which is manifested in the reduction of the duration of relapse 1.4 times prolongation of remission in 3 times and milder disease. Carried out in the dynamics fibrogastroduodenoscopy after treatment showed that 100% of the observed total endoscopic remission which is manifested in the disappearance of opalescent gray overlay on the bottom of the ulcer and ulcer epithelization.

Dietary intervention in chronic fatigue syndrome.

BACKGROUND: Anecdotal reports and books have been published linking an over growth of Candida Albicans with chronic fatigue syndrome (CFS), suggesting dietary change as a treatment option. Little scientific data has been published to validate this controversial theory. This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life (QoL) in individuals with CFS. METHODS: A 24-week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions. Primary outcome measures were fatigue as measured by the Chalder Fatigue Score and QoL measured by Medical Outcomes Survey Short Form-36. RESULTS: A high drop out rate occurred with 13 participants not completing the final evaluation (7HE/6LSLY). Intention to treat analysis showed no statistically significant differences on primary outcome measurements. CONCLUSION: In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE. Given the difficulty with dietary compliance experienced by participants, especially in the LSLY group, it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime.

Influence of diet on the shedding of Candida glabrata by experimentally infected preweaned calves.

The influence of three diets, comprising dam's milk (DM) from the same farm, commercial milk replacer with (CMRL) or without 3.2% lactose (CMR), on the duration and intensity of Candida glabrata shedding in the faeces of preweaned calves following experimental oral infection was examined. Shedding of other potential enteric pathogens was also monitored. The duration and intensity of C. glabrata shedding in DM-fed calves were reduced significantly compared with the calves fed the two diets based on milk replacers. Consequently, feeding calves with DM might disrupt the infective cycle, resulting in the yeast's elimination from a farm. In the CMR and CMRL groups, the periods of intensive shedding of C. glabrata and rotavirus overlapped but no diarrhoea was associated with the shedding of either microorganism. There was no evidence that lactose diminished colonization in vivo.

[Hypersensitivity to "Candida albicans" and other fungi in patients with chronic urticaria]. / Hipersensibilidad a "Candida albicans" y otras levaduras en pacientes con urticaria crónica

Considering the high incidence of chronic urticaria among female patients and the frequent difficulty in identifying the etiologic factor of factors the author decided to investigate the possible role of Candida albicans and other yeasts usually found as contaminants in certain foods and beverages or purposely cultivated for industrial products, as the sensitizing agents leading to the clinical picture of chronic urticaria. One hundred female patients with urticaria which had persisted for more than 6 weeks were selected and investigated, disregarding those with dermographism or cholinergic and cold urticaria. Aside from a careful history and laboratory tests to complement the physical examination that could rule out chronic bacterial infectious foci, intestinal parasitic infestation and thyroid disorders, intradermal skin tests with standard doses of Candida albicans and Saccharomyces cerevisiae and other common environmental and food allergens were done. The patients' age ranged from 4 to 70 years. The skin tests sites were examined for Type I reactions at 15 and 20 minutes; for Type III reactions at 8 and 12 hours; and for Type IV reactions at 48 and 72 hours. When tested with Candida albicans antigen, 35% had Type I/III reactions and 60% presented Type IV reaction. When Saccharomyces cerevisiae antigen was used for testing, 29% had Type I/III reactions and none presented Type IV. Forty-nine of the sixty patients who presented Type IV reaction to Candida albicans had in the past significant vaginal discharge (or vaginal symptoms: burning, itching) that obliged the patients to consult a gynecologist, but only ten had stained smears and cultures from the vaginal secretions and four were told to have a monilia vaginal infection confirmed by the microbiological tests, although forty of them received Nistatin therapy at the time of the gynecological complaints. At the time the patients were seen by the allergist, complaining about urticaria, only four had symptoms and signs of monilia infection and were confirmed by culture: one presented oral moniliasis following broad-spectrum antibiotic, two had vaginal moniliasis developing right after their menstrual period; one had intestinal and cutaneous manifestations (perineal and crural) developing also after broad-spectrum antibiotic therapy. All the four patients had exacerbation of the urticaria while undergoing the monilia infection. After 1-2 weeks of elimination diet, each patient was challenged with yeasts-containing foods (bread, buns, sausages, beer, wines, grapes, cheese, vinegar, tomato catsup). Twenty-five patients (71%) of the group who positively reacted with a Type I/III reaction when tested with Candida antigen, showed a positive provocation test (reappearance of urticaria) and twenty patients (69%) of the group who reacted with Saccharomyces had a positive challenge test...