Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis.

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 (I2 > 50.00%, P < 0.01), except for caspofungin (I2 = 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).

Oral Candida albicans strain diversity and maintenance in HIV positive women in South Africa.

OBJECTIVE: This study investigated C. albicans strain diversity and maintenance in the oral cavity of HIV positive women over a 6 month period. STUDY DESIGN: C. albicans strains were isolated from 17 HIV positive women at Charlotte Maxeke Academic Hospital, Johannesburg at 3 intervals over a 6 month period. Strains were genotyped using ABC and Multilocus Sequence Typing (MLST) techniques. In the MLST technique, for each strain, a Diploid Sequence Type (DST) number was obtained. Using cluster analysis, an Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrogram and a matrix of strain similarities were generated. Strains were also compared to the previous South African isolates documented in the MLST database. RESULTS: Ninety four percent of women carried the same ABC genotype for 6 months. MLST technique, showed that ten women (58.8%) carried the same DST at 2 visits, while seven (41.2%) carried different DST at all visits. Further analysis showed that 64.7% of women were recolonised with different strains and 35.3% carried the same strains of C. albicans with heterozygosity. A total of 40 diploid sequence types were identified of which 27 DSTs were unique to this study group that were added to the MLST database. Most of the strains were closely related to previously isolated strains from South Africa. CONCLUSION: Recolonization of the oral cavity with different strains and microevolution of the original strains of C. albicans can occur, which can be a potential problem for HIV patients, in whom highly virulent and drug resistant strains can emerge.

Effectiveness of a tissue conditioner containing antifungals in a rat model of denture stomatitis.

AIM: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis. METHODS AND RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for 4 days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or ß-cyclodextrin-complexed (ßCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices, one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After 4 days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:ßCD, and Chx groups presented a significant decrease in the microbial load compared with the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group. CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.

Coptidis rhizoma extract alleviates oropharyngeal candidiasis by gC1qR-EGFR/ERK/c-fos axis-induced endocytosis of oral epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis rhizoma, first recorded in the "Shen Nong's Herbal Classic", is one of the traditional Chinese medicine (TCM) used to treat infectious diseases, with reputed effectiveness against oropharyngeal candidiasis (OPC). Studies have demonstrated the inhibitory properties of C. rhizoma (CRE) against Candida albicans, yet there is limited information available regarding its treatment mechanism for OPC. AIM OF THE STUDY: Our previous research has suggested that CRE can prevent the formation of C. albicans hyphae and their invasion of the oral mucosa, thereby exerting a therapeutic effect on OPC. Nevertheless, the precise therapeutic mechanisms remain incompletely understood. Previous studies have revealed that a receptor for globular heads of C1q (gC1qR), a crucial co-receptor of the epidermal growth factor receptor (EGFR), facilitates the EGFR-mediated internalization of C. albicans. Therefore, this study aims to investigate the potential mechanism of action of CRE and its primary component, berberine (BBR), in treating OPC by exploring their effects on the gC1qR-EGFR co-receptor. MATERIALS AND METHODS: To identify the chemical components of CRE, we utilized Ultra-high performance liquid chromatography in conjunction with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MSE), revealing the presence of at least 18 distinct components. To observe the therapeutic effects of CRE on OPC at the animal level, we employed hematoxylin and eosin staining, periodic acid-Schiff staining, scanning electron microscopy, and fungal load detection. Subsequently, we evaluated the anti-inflammatory properties of CRE and its main component, BBR, in treating OPC. This was achieved through enzyme-linked immunosorbent assay (ELISA) both at the animal and cellular levels. Additionally, we assessed the ability of C. albicans to disrupt the epithelial barrier of FaDu cells by studying the protective effects of BBR on the fusion barrier using the transwell assay. To further explore the underlying mechanisms, we analyzed the effects of BBR on the gC1qR-EGFR/extracellular signal-regulated kinase/c-Fos signaling pathway at the cellular level using qRT-PCR, western blotting, and immunofluorescence. Furthermore, we validated the effects of BBR on the gC1qR-EGFR co-receptor through ELISA, qRT-PCR, and western blotting. Finally, to confirm the outcomes observed at the cellular level, we validated the impact of CRE on the gC1qR-EGFR co-receptor in vivo using qRT-PCR, western blotting, and immunofluorescence. These comprehensive methods allowed us to gain a deeper understanding of the therapeutic mechanisms of CRE and BBR in treating OPC. RESULTS: Our findings indicate that CRE and its primary component, BBR, effectively alleviated the symptoms of OPC by modulating the gC1qR-EGFR co-receptor. The chemical composition of CRE and BBR was accurately identified using UPLC-Q/TOF-MSE. The gC1qR-EGFR co-receptor plays a crucial role in regulating downstream signaling pathways, emerging as a potential therapeutic target for OPC treatment. Through both in vitro and in vivo experiments, we explored the therapeutic potential of CRE and BBR in OPC. Additionally, we employed overexpression and silencing techniques to confirm that BBR can indeed influence the gC1qR-EGFR co-receptor and regulate the gC1qR-EGFR/extracellular signal-regulated kinase (ERK)/c-Fos signaling pathway, leading to improved OPC outcomes. Furthermore, the significance of CRE's effect on the gC1qR-EGFR co-receptor was validated in vivo. CONCLUSION: Our study demonstrates that CRE and its main component, BBR, can effectively alleviate OPC symptoms by targeting the gC1qR-EGFR heterodimer receptor. This discovery offers a promising new therapeutic approach for the treatment of OPC.

IMPROVEMENT OF THE METHODOLOGY OF BIOMATERIAL COLLECTION FOR THE DIAGNOSIS OF THE ORAL CAVITY MUCOSA DISEASES.

Aim - to improve the methodology for collecting material from lesions of the oral mucosa for exfoliative cytological examination. A group of patients diagnosed with B37.0 Candida stomatitis was examined. To clarify the diagnosis, various methods of collecting biological material from the tongue of patients were used, namely, the method using a cytobrush with subsequent fixation of cytological material on a slide. The microbiota of the back of the tongue was analyzed in 12 patients with glossitis and 12 healthy subjects (the control group). The microscopic method of research was used - using an immersion microscope MICROmed@XS-3330, and the morphological and tinctorial properties of microorganisms were determined. In ten fields of view, the number of leukocytes, the nature of epithelial cells, and the presence of various microorganisms were detected and counted. A comparison of the quality of the use of the microscope method for the study of the tongue microbiota of patients with candidal glossitis was performed under the conditions of taking pathological material using a dental scalpel and an oral cytobrush. For a reasonable interpretation of the results and determination of their significance, a statistical analysis was performed to determine the frequency of detection of microorganisms in patients with glossitis and healthy subjects, depending on the nature of the material taken from the back of the tongue using a dental scalpel or cytobrush. The studies showed that the etiologic structure of glossitis pathogens was dominated by Candida yeast-like fungi, but cases of leptotrichosis aetiology were observed (16.7%). Monococci and gram-negative monobacteria were detected in all studied groups. An increase in the diversity of microorganisms was found when the material was taken with a cytobrush. The microbiota of all subjects differed depending on the type of instrument used for sampling. Thus, in the group of healthy individuals, the interdental brush helped to detect twice as many streptococci as a scalpel. In patients with candidiasis, a brush biopsy showed a 2.7-fold increase in gram-positive diplococci, twice as many streptococci and gram-positive bacilli, three times as many staphylococci, 2.25 times as many clusterforming gram-negative cocci, and 2.3 times as many gram-negative diplococci. A significant increase in the diversity of microorganisms was observed with the cytobrush compared to the use of a dental scalpel. In patients with glossitis, the accumulation of keratinized epithelial cells was significantly higher compared to the presence of young cells in healthy subjects, regardless of the method of sampling.

Evaluation of some immunological markers in co-infection of COVID-19 with thrush candidiasis.

OBJECTIVE: COVID-19 infection poses significant risks, including life-threatening consequences and fungus synchronization, making it a significant concern. This study seeks to assess the effect of concurrent infection of COVID-19 with Thrush Candida albicans on the patient's health state by measuring the proportion of immune cells and certain interleukins such as IL-8, -10, -17, and -33. METHODS: The study involved 70 patients (30 patients with COVID-19, 17 patients with thrush candidiasis, and 23 patients with Thrush Candida albicans) and 50 healthy individuals as a control group. COVID-19 was identified using RT-PCR, while C. albicans were identified through culture media, biochemical testing, and oral swabs. Ruby equipment and ELISA kits were used for blood counts and interleukin detection. RESULTS: COVID-19, thrush candidiasis, and Thrush Candida albicans infections occur in a wide range of age groups (4-80 years), with no significant differences between sexes (p>0.05). Immunologically, our study found that Thrush Candida albicans patients had the highest rate of neutrophils (89.6%) and basophils (2.01%), while corona patients had the highest percentage of lymphocytes (70.12%) and eosinophils (7.11%), and patients with thrush candidiasis had the highest percentage of monocytes. Thrush Candida albicans patients showed increased IL-8 (56.7 pg/mL) and IL-17 (101.1 pg/mL) concentrations, with the greatest concentration of IL-33 (200.5 pg/mL) in COVID-19, and a decrease in the level of IL-10 in patient groups compared with controls. CONCLUSION: Patient groups showed increased neutrophils, lymphocytes, monocytes, and IL-8 levels, with a significant linear association between proinflammatory interleukins and these cells.

Antimicrobial photodynamic therapy using a low-power 650 nm laser to inhibit oral Candida albicans activity: an in vitro study.

This study assessed the efficacy of antimicrobial photodynamic therapy (PDT) using a 650 nm diode laser combined with methylene blue (MB) as a photosensitizer to inhibit the growth of Candida albicans (C. albicans). Oral samples were collected from 75 patients diagnosed with oral thrush. C. albicans was isolated and identified using traditional methods and the VITEK 2 YST system. Samples (n = 25) were divided into five groups: Group 1 (control, n = 5) consisted of C. albicans suspensions in saline; Group 2 (n = 5) treated with nystatin; Group 3 (n = 5) exposed to a 650 nm diode laser in continuous mode at 200 mW for 300 seconds; Group 4 (n = 5) treated with 650 nm laser and MB as a photosensitizer; Group 5 (n = 5) exposed to the laser in combination with nystatin. Statistical analysis using ANOVA, Dunnett's t-test (P = 0.05), and LSD (P = 0.001) revealed significant differences in C. albicans counts pre- and post-treatment. Group 5 showed the most significant reduction in C. albicans, followed by Group 4, while Groups 2 and 3 showed the least variation. The findings suggest that PDT using a 650 nm diode laser with methylene blue (in continuous mode at 200 mW for 300 seconds) effectively reduced the prevalence of C. albicans.

Oral candidiasis in liver transplant patients: species identification and antifungal susceptibility profile.

OBJECTIVE: This study aimed to verify oral candidiasis, identify the causative species, and investigate the antifungal susceptibility of yeasts isolated from liver transplant patients. METHODS: A descriptive analysis of 97 patients who underwent liver transplantation was conducted at a hospital. Two clinical examinations (Collections A and B) of the oral cavity were performed. Oral material was collected from all patients, inoculated in Sabouraud Dextrose Agar, and incubated at 35℃ for 48 hours. Samples were identified by molecular sequencing of the internal trascribed space region of rDNA. RESULTS: An antifungal susceptibility test with fluconazole, amphotericin B, and micafungin was performed using the Clinical and Laboratory Standards Institute yeast broth microdilution method. Among the patients, 15 presented with oral candidiasis: eight in Collection A and seven in Collection B. The primary type of candidiasis was atrophic, followed by pseudomembranous candidiasis. The most prevalent species was Candida albicans (nine), followed by Candida glabrata (three), Candida tropicalis (two), and Candida dubliniensis (one). Regarding susceptibility to fluconazole, of the 15 samples, 11 were susceptible, three were susceptible in a dose-dependent manner, and one was resistant. CONCLUSION: The most commonly identified type of candidiasis was atrophic, with C. albicans and C. glabrata being the most prevalent causative species. One fluconazole-resistant isolate each of C. tropicalis and C. albicans were identified.

Infant Oral Candidiasis and Bottle Cleaning Methods: A Descriptive Study.

As manufacturers produce bottles with additional parts, such as an anticolic straw, cleaning time increases. Increased cleaning time potentially decreases cleaning effectiveness and, thus, increases the chance for thrush. This study explored the relationship between the number of bottle parts and cleaning methods for bottle-fed-only infants (<13 months) presenting with oral candidiasis. After obtaining demographic information on eligible infants (via parental consent) from the chart, caregivers of 60 infants verbally completed a questionnaire. The questionnaire elicited information about the preferred bottle for feeding, number of parts, washing frequency, washing method, drying method, sterilization frequency, and sterilization method. The χ2 test, and Fisher's exact test when necessary, was performed to examine the relationship between each reported cleaning method (washing, drying, and sterilization) compared with the number of bottle parts (≤3 or ≥4). The number of bottle parts showed no association with bottle cleaning methods (p > .05). Although there were no statistically significant relationships, trends did present that warrant investigation. Future studies to confirm recommended practices for cleaning methods and identify those at risk from demographic data could positively affect the health of bottle-fed infants by reducing the occurrence of thrush.

The inhibitory effects of carvacrol, nystatin, and their combination on oral candidiasis isolates.

BACKGROUND: Candida, a common oral microbiota, can cause opportunistic fungal infections. With rising Candida infections and limited effective antifungals, new treatments are needed. This study investigates carvacrol essential oil's effect on oral candidiasis, alone and with nystatin, compared to nystatin alone. MATERIALS AND METHODS: In this study, oral samples were collected from dental clinic patients, especially denture users. The presence of Candida was confirmed and cultured from these samples. Candidiasis was detected by observing Candida colonies. Drug sensitivity was tested on 100 positive samples. The minimum concentration of inhibition and lethality of each isolate was evaluated using nystatin and carvacrol. The results were compared using two-way analysis of variance. Finally, the minimum inhibitory concentration (MIC) of nystatin and carvacrol was calculated individually and in combination. RESULTS: The present study found that Candida albicans and non-albicans species were equally prevalent. Carvacrol showed significant biological activity against all Candida species, with an average MTT of 50.01%. The average MIC value of carvacrol was 24.96 µg/ml, indicating its potential to inhibit Candida growth. The mean Minimum Fungicidal Concentration (MFC) value of carvacrol was 23.48 µg/ml, suggesting its effectiveness in killing the fungi. CONCLUSION: The study's findings reveal that the MIC of carvacrol was significantly lower than that of nystatin and the combination of nystatin and carvacrol. This suggests that carvacrol holds potential as an effective herbal remedy for candidiasis.

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

Bimekizumab in psoriasis: a monocentric study evaluating short- and mid-term effectiveness and safety profile in a real-world setting.

INTRODUCTION: Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited. MATERIALS AND METHODS: An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab. RESULTS: At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis. CONCLUSION: Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.

Common Oral Conditions: A Review.

Importance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. Observations: In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1ß (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1ß (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Conclusions and Relevance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.

BACKGROUND: Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis. METHODS: In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test. RESULTS: The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P >  0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P <  0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value <  0.000. CONCLUSIONS: This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions. TRIAL REGISTRATION: NCT06072716 with first registration first registration in 10/10/2023.

Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Holotoxin A1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans.

BACKGROUND AND PURPOSE: The holotoxin A1, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A1 against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis. EXPERIMENTAL APPROACH: The antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A1 in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice. KEY RESULTS: Holotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A1 inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models. CONCLUSION AND IMPLICATIONS: Holotoxin A1 is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.

Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL.

OBJECTIVES: To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors. METHODS: Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52. RESULTS: A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to |52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52. CONCLUSIONS: Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.

Vitamin D deficiency and oral candidiasis in patients with HIV infection: A case‒control study.

BACKGROUND: Oral candidiasis is a common opportunistic infection in patients with human immunodeficiency virus (HIV). In addition, most of these patients suffer from vitamin D deficiency. This study aimed to investigate the association between vitamin D levels and oral candidiasis in patients with HIV infection. METHODS: This case‒control study was conducted on HIV-infected patients. Cases were patients with oral candidiasis diagnosed based on physical examinations. Controls were age- and sex-matched individuals without oral candidiasis. The levels of 25-OH vitamin D and other laboratory markers (CD4 count and viral load) were compared between the case and control groups. RESULTS: A total of 104 cases and 102 controls were included in the study. The cases had significantly lower 25-OH vitamin D3 levels (MD = 33.86 ng/mL, 95% CI= (31.85, 35.87), P < 0.001) and CD4 counts (MD = 267.48 cells/mm3, 95% CI= (189.55, 345.41), P < 0.001) than the controls. In addition, viral load was significantly higher in cases than in controls (MD = 7.03 × 105 copies/mL, 95% CI= (4.46 × 105, 9.61 × 105), P < 0.001). The multivariate logistic regression analysis revealed that educational status (OR = 0.032, 95% CI= (0.002, 0.100), P < 0.001), current HAART (OR = 0.005, 95% CI= (0.001, 0.014), P < 0.001), history of oral candidiasis (OR = 20.114, 95% CI= (18.135, 21.957), P < 0.001), CD4 count (OR = 0.004, 95% CI= (0.001, 0.006), P < 0.001), viral load (OR = 12.181, 95% CI= (1.108, 133.392), P < 0.001), and vitamin D level (OR = 0.011, 95% CI= (0.008, 0.015), P < 0.001) were significantly associated with the risk of developing oral candidiasis. CONCLUSIONS: Based on the findings, most patients with HIV infection suffer from vitamin D deficiency, especially those with oral candidiasis. Hypovitaminosis D was significantly associated with an increased risk of oral candidiasis. Thus, vitamin D supplementation may assist HIV-positive patients in improving their oral health and preventing oral candidiasis.

Immunity to pathogenic mucosal C. albicans infections mediated by oral megakaryocytes activated by IL-17 and candidalysin.

The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes (Mks) in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident Mks. Interleukin-17, important in antifungal immunity, was required since mice lacking the IL-17 receptor had decreased circulating platelets and their oral Mks did not expand during OPC. The secretion of the peptide toxin candidalysin activated human Mks to release platelets with antifungal capacity. Infection with a candidalysin-deficient strain resulted in decreased expansion of tongue Mks during OPC. This is the first time that a distinct megakaryocyte population was identified in the oral mucosa which is critical for immunity against fungal infection.