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The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health.

Objective: The aim of the study is to assess the effect of probiotic bacteria on oral Candida counts in cancer patients who are undergoing head- and neck-radiotherapy in a tertiary care center. Study Design: The study was a randomized clinical trial including 90 patients who just completed head- and neck-radiotherapy. Materials and Methods: Participants were randomly allocated into three equal sized groups, i.e., probiotics group, candid group, and combination groups. Oral rinse samples of the patients were collected before and after the intervention for the identification of Candida. The samples were incubated on Sabouraud's Dextrose Agar with Chloramphenicol at 37°C for 48 h, to assess the counts of colony-forming units/milliliter (CFU/ml) of Candida in saliva, and further on chrome agar plates to identify the Candida spp. Data were analyzed using mixed ANOVA to compare mean CFU/ml of Candida among three groups before and after the intervention. Results: A total of 86 patients were included in the final analysis and there was a statistically significant reduction in mean Candida spp. Counts (CFU/ml) after intervention in all the three groups (P = 0.000) and significant reductions identified in both probiotic and combination therapy groups. Apart from reduction in Candida albicans, significant decrease in Candida glabrata and Candida tropicalis was observed after probiotics usage compared to other groups. Conclusions: The present study suggests that probiotic bacteria were effective in reducing oral Candida spp which can be recommended alone or in combination with traditional antifungal agents for effective reduction in oral Candida in head- and neck-radiotherapy patients.

Background Opportunistic fungal infections like oral candidiasis account for a significant amount of morbidity in HIV disease and an indicator of immune suppression. Fluconazole is a broad-spectrum antifungal agent that has been extensively used in the management of oral, candidiasis. Highly efficacious fluconazole is also known to have systemic toxicity due to high drug interaction and hence the present study focuses on the formulation of bioadhesive film as a controlled release carrier for fluconazole. Materials and Methods Patients were randomised, using a computer-generated list of random numbers, into one of the three groups: patients in group A received fluconazole mucoadhesive film 20 mg (sustained release) that was to be applied at bedtime and film 10 mg (intermediate release) to be applied during the day after lunch. Results There was a significant decrease in oral discomfort, pain and clinical improvement in group A compared to group B (Fluconazole oral tablets 100 mg/day) (P = 0.005) and group C (Fluconazole Mouth rinse) (P = 0.002). The patients who received the mucoadhesive patches had a more tolerable safety profile as expected compared to the other groups. Conclusion The bioadhesive films of fluconazole were used in HIV positive patients with oral candidiasis to overcome the problems of high dose requirement of the drug and reduce associated adverse reactions in an already immunocompromised patients and improve the quality of life. Plain Language Summary Treating Oral Fungal infections in the mouth using Mucobioadhesive patch that contains a strong antifungal infection preventing complications and also improving patients symptoms and quality of life Fungal infections in the mouth can be disabling to HIV positive patients as it presents with severe burning sensation and intolerance to spicy food. As a part of treating this fungal infection named oral candidiasis an antifungal medication is usually presribed, either for topical application or for oral intake. If any systemic medication is given, it causes other side effects in an already immunocompromised person, hence, a new formulation is used called Mucobioadhesive patch that contains a strong antifungal action preventing complications and also improving patients symptoms and quality of life.

Background and Aim: Ozone is highly valued for various therapeutic applications such as antimicrobial, antihypoxic, analgesic, and immunostimulating for more than a century in the medical profession. Ozone therapy is now gaining a strong foothold in dentistry. Ozone has bactericidal, fungicidal, and virucidal properties. Oral candidiasis is one of the most common opportunistic fungal infections of the oral cavity. Hence, a study was conducted to evaluate and compare the ability of ozonated water and topical clotrimazole in reducing the Candidal species colony-forming unit (CFU) count in oral candidiasis. Materials and Methods: The study included 40 candidiasis patients of either sex aged between 18 and 60 years attending the Department of Oral Medicine and Radiology. The patients were randomly assigned to either topical ozone therapy or topical clotrimazole groups. Salivary Candidal CFU counts were assessed during and after the treatments. Results and Conclusion: There was gradual but significant reduction in Candidal CFU count in both groups. At the end of the treatment, Candidal CFU count reduction in ozone group (60.5% reduction) was more than the clotrimazole group (32.3% reduction). 14 patients (70%) with candidiasis in ozone group were reduced to 6 (30%) whereas only 8 patients (40%) out of 13 (65%) in clotrimazole group, although intergroup comparison was not statistically significant. Ozone therapy was much more effective in reducing the patients with candidiasis to a state of carriers. These findings suggest that ozonated water might be useful to treat oral candidiasis.

Objectives Candida albicans is a common fungal infection and is commensal in 40–65 % of healthy adults. The development and pharmacokinetics of a novel sustained release clotrimazole varnish (Clot-SRV) for topical oral use have been reported. The aim of this study was to compare the efficacy of this varnish with clotrimazole troche treatment of oral candidiasis. Materials and methods Of the 12 patients with denture stomatitis treated for 14 days, six used Clot-SRV (study group) and six clotrimazole troches (control). The patients were instructed to use Clot-SRV (50 mg of clotrimazole) once a day, and the control group was instructed to use five troches of 10 mg clotrimazole/day. Microbiological samples were obtained from saliva, buccal mucosa, palate, and denture. The degree of erythema was recorded at three time points, and subjective opinions noted using a questionnaire. Results At the end of the study, the control group had relatively more cases of erythema on all examined surfaces; patients who applied the Clot-SRV had significantly lower levels of candida on the denture surfaces and in saliva, and had better compliance to the medication. Conclusions The novel clotrimazole sustained release varnish may be an important part of a new protocol for oral candidiasis, with improved clinical outcomes.

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti- C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans . Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4′,6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid–Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

Background. In human immunodeficiency virus (HIV)–infected patients, fluconazole prophylaxis is associated with reductions in the rate of fungal infection. However, concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment—refractory infections. Methods. We performed a randomized, open-label trial that compared oral fluconazole given continuously (200 mg 3 times weekly; the “continuous fluconazole arm”) with fluconazole that was provided only for episodes of orophayngeal candidiasis (OPC) or esophageal candidiasis (EC) (the “episodic fluconazole arm”) in HIV-infected persons with CD4+ T cell counts of <150 cells/mm3 and a history of OPC. The primary study end point was the time to development of fluconazole-refractory OPC or EC, which was defined as lack of response to 200 mg fluconazole given daily for 14 or 21 days, respectively. Results. A total of 413 subjects were randomized to receive continuous fluconazole, and 416 were randomized to receive episodic fluconazole. After 42 months, 17 subjects (4.1%) in the continuous fluconazole arm developed fluconazole-refractory OPC or EC infections, compared with 18 subjects (4.3%) in the episodic fluconazole arm, with no difference between treatment arms with regard to the time to development of a fluconazole-refractory infection within 24 months (P = .88, by log-rank test) or before the end of the study (P = .97, by the log-rank test). Continuous fluconazole therapy was associated with fewer cases of OPC or EC (0.29 vs. 1.08 episodes per patient-year; P < .0001) and fewer invasive fungal infections (15 vs. 28 episodes; P = .04, by χ2 test), but not with improved survival, compared with episodic fluconazole therapy. Conclusion. Continuous fluconazole therapy is not associated with significant risk of fluconazole-refractory OPC or EC, compared with episodic fluconazole therapy, in HIV-infected patients with access to active antiretroviral therapy.

Comparative metabolomics may shed light on host immunity and biology in oral candidiasis (oral thrush). Untargeted metabolomic analyses were performed on oral rinses collected from 26 primary oral candidiasis patients (OT), 12 patients after antifungal treatment (AT), and 12 unaffected individuals (C). Host immune modulation metabolites against oral candidiasis , Candida virulence and antifungal properties were identified. The upregulation of C17 sphinganine, L-leucine, monoacylglycerol, phosphatidylethanolamine, and spermine, in OT and AT groups, highlights the role of host immunity in Candida clearance. The altered sphingolipid levels suggest disrupted membrane integrity and immune function, while dysregulated amino acid, purine, and glutathione metabolism reflect oxidative stress and inflammation. Antifungal metabolites, specifically dichloroacetate, 1-monopalmitin, and undecane-2-one, were significantly upregulated in the OT group; conversely, fatty acids (palmitic amide, linoleamide, stearamide, and pentadecanal) were downregulated. Metabolomic similarities between oral candidiasis and xerostomia were evident, with shared markers such as L-valine, L-leucine, D-proline and 4-hydroxyphenylpyruvic acid. Increases in lipid metabolites, carboxylic acids, and amino acids, particularly L-leucine and hypoxanthine in patients upon resolution of oral candidiasis following antifungal treatment suggests fungal clearance, immune activation and recovery from oxidative stress. Some metabolites identified in oral candidiasis patients have reported roles in oral carcinogenesis, however, the findings remain observational and warrant further validation. Our results demonstrate that oral candidiasis is associated with distinct metabolomic alterations compared with healthy controls, and that antifungal therapy reshapes the oral metabolic profiles via complex host–microbiome–fungal metabolic pathways. The identification of oral candidiasis-associated metabolites also highlights their potential as non-invasive biomarkers and therapeutic targets for oral healthcare.

Background Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients. Methods Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model. Results Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1–35.8%), fluconazole (24.8%, 95% CI: 17.4–32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0–26.0%), voriconazole (20.0%, 95% CI: 1.9–38.0%), miconazole (15.0%, 95% CI: 5.1–26.0%), clotrimazole (13.4%, 95% CI: 2.3–24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5–5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I 2  > 50.00%, P  < 0.01), except for caspofungin (I 2  = 0.00%, P  = 0.65). Conclusions Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin. Registration The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).

Aloe vera (L.) Burm.f. is a traditional Chinese medicine known for treating various ailments, including fungal infections. Aloin is one of the major components from A. vera , but its antifungal mechanism and therapeutic potential against oral candidiasis are not clear. This study aimed to examine the mechanism of aloin against Candida albicans and its inhibitory activity against oral candidiasis. In this study, we for the first time found that aloin could induce the formation of abnormal hyphae with smaller hyphal diameters and fewer branching points in C. albicans including 11 clinical isolates without growth inhibition. The transcriptome and further cell wall contents analysis indicated that aloin remodeled the cell wall to increase the contents of β-1,3-glucan and furtherly showed an antagonistic effect with micafungin. Aloin also significantly inhibited the cell damage of oral epithelial cells and oral candidiasis in mice infected by C. albicans due to its inhibitory actions on the hyphal development and expressions of virulence factors, including candidalysin (coded by ECE1 ). Our results suggest that aloin is a promising antifungal agent for controlling candidiasis and targeting hyphal development and pathogenesis represents a practical strategy for developing new antifungal drugs. Key points • Aloin remodels the C. albicans cell wall to form avirulent hyphae. • Aloin inhibits C. albicans infections in oral epithelial cells and mouse mucosa without toxicity. • Aloin is a promising antifungal agent with therapeutic potential against C. albicans infections. Graphical Abstract