Search Results (27)

Inhaled corticosteroids (ICSs) are widely used to manage chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and human immunodeficiency virus (HIV). However, prolonged use of ICS is associated with the development of oropharyngeal candidiasis, a fungal infection primarily caused by Candida albicans, due to local immunosuppression in the oral cavity. The incidence of oropharyngeal candidiasis varies depending on geographic region, patient age, and comorbidities, with immunocompromised individuals, those with diabetes, and the elderly being particularly vulnerable. Key risk factors include high ICS doses, poor oral hygiene, and improper use of inhalers. Prevention is the cornerstone of managing oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids. Patient education on proper inhaler technique and oral hygiene is essential to reduce the risk of fungal overgrowth in the oral cavity. Additional preventive strategies include the use of spacers, mouth rinsing after inhalation, and proper denture care. In cases where these measures fail to prevent the infection, prompt detection and early intervention are crucial to prevent progression or recurrence. This narrative review aims to analyze the most effective prophylactic measures to prevent oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids, emphasizing patient education, oral hygiene, and proper use of inhalation devices. Full article

Backgrounds and objective: Disorders in the stomatognathic system and otorhinolaryngologic manifestations are frequently observed in individuals living with HIV. Ear, neck, and throat (ENT) signs and symptoms often serve as critical markers of treatment failure, particularly in the advanced stages of HIV infection. This article aims to evaluate and consolidate recent developments in the treatment and management of otorhinolaryngological manifestations in HIV-positive patients. Materials and methods: We carried out a retrospective clinical investigation of patients admitted with HIV/AIDS in the northeastern region of Romania, hospitalized in the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi. We followed the viro-immunological status correlated with patients’ otolaryngology and dental symptomatology, aiming to emphasize the comorbidities of HIV/AIDS cases. The study period spanned from 1 January 2020 to 30 November 2024. Results: There were a total of 552 recorded cases of oropharyngeal manifestations in patients with HIV. They were more frequent in men (358 cases, 64.85%) than women (194 cases, 35.15%). The majority of cases were young adults, aged 30 to 39 years, comprising 255 patients (46.19%), and most cases (36.85%) had CD4+ T-lymphocyte values between 200 and 499 cells/μL. The most frequent diagnosis was oral candidiasis, recorded in 335 male and 174 female cases (509, 92.21% total). Other notable conditions included gingivitis/periodontitis, sinusitis/rhinosinusitis, mastoiditis, and dental abscesses, albeit at lower frequencies. Notably, antifungal therapy with fluconazole was the most frequently employed treatment, followed by aminopenicillins and fluoroquinolones. With respect to the antiretroviral treatment, 83.69% of cases were prescribed a single-pill regimen. Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach, including an ENT specialist and access to antiretroviral therapy. Full article

Candida albicans (C. albicans) is a major opportunistic fungal pathogen that causes life-threatening infections, particularly in immunocompromised individuals, underscoring the critical need to understand its pathogenic mechanisms. This study investigates the role of Cas5, a key transcription factor, in regulating C. albicans cell wall remodeling, virulence, and host interactions. Genetic manipulation and biochemical assays were used to examine the effects of Cas5 depletion on C. albicans cell wall structure, adhesion to host cells, morphology transition, innate immune cells recruitment, and pathogenicity in a BALB/C mouse model of oropharyngeal candidiasis (OPC). The results showed that the Cas5 depletion mediated β-glucan exposure and enhanced C. albicans’s ability to recruit neutrophils in vivo. Additionally, Cas5-mediated changes in cell surface hydrophobicity (CSH), CWP expressions, and morphological transition promoted C. albicans adhesion to biologically active surfaces (host cells) and increased fungal burden in the mouse model of OPC. In conclusion, Cas5 modulates C. albicans cell wall remodeling by masking cell wall β-glucan, altering CSH, and regulating the expression of cell wall proteins (CWPs). Additionally, Cas5 participates in inhibiting neutrophil recruitment and enhancing the C. albicans adhesion to host cells, as well as facilitating morphological transitions. These actions promote the colonization and invasion of C. albicans in OPC pathogenesis. Full article

Background and Objectives: The aim of this study was to identify specific rhino- and oropharyngeal microbiological pathogens as well as associated comorbidities that favor SARS-CoV-2 infection and corelate them. Materials and Methods: This prospective clinical study enrolled 61 patients (28 COVID-19-positive and 33 controls) who were tested for other comorbidities and co-existence of associated oral pathogenic microbiota. Results: A total of 247 bacterial isolates were identified in the bacterial cultures in both groups. Viral hepatitis type A was more prevalent in the COVID-19-positive group (p = 0.026), as was the presence of oral candidiasis (p = 0.006). In the control group, a moderate direct relationship was observed between the Beta hemolytic streptococcus group G and dermatitis, and strong direct relationships were observed between the Beta hemolytic streptococcus group G and external otitis, Streptococcus pyogenes and dental alveolitis, and Streptococcus pyogenes and chronic lymphocytic leukemia. In the test group, strong direct relationships were observed between Hemophilus influenzae and pulmonary thromboembolism; Staphylococcus aureus and autoimmune thyroiditis; post-viral immunosuppression, chronic coronary syndrome, and hypernatremia; Beta hemolytic streptococcus group C and rheumatoid polyneuropathy; Beta hemolytic streptococcus group G and hyperkalemia, hypothyroidism, secondary anemia, and splenomegaly; and active oral candidiasis and SARS-CoV-2 viral pneumonia. The following relationships were strong, but inverse: Beta hemolytic streptococcus group G and acute respiratory failure, and active oral candidiasis and SARS-CoV-2 viral bronchopneumonia. Conclusions: Briefly, COVID-19-positive patients have the predisposition to build up associated comorbidities and coinfections, which can be the expression of the immune burden that this virus generates to the host. Full article

Oral candidiasis encompasses fungal infections of the tongue and other oral mucosal sites with fungal overgrowth and its invasion of superficial oral tissues. Borneol was assessed in this research as the matrix-forming agent of clotrimazole-loaded in situ forming gel (ISG) comprising clove oil as the co-active agent and N-methyl pyrrolidone (NMP) as a solvent. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, gel formation, and drug release/permeation, were determined. Their antimicrobial activities were tested using agar cup diffusion. The pH values of clotrimazole-loaded borneol-based ISGs were in the range of 5.59–6.61, which are close to the pH of 6.8 of saliva. Increasing the borneol content in the formulation slightly decreased the density, surface tension, water tolerance, and spray angle but increased the viscosity and gel formation. The borneol matrix formation from NMP removal promoted a significantly (p < 0.05) higher contact angle of the borneol-loaded ISGs on agarose gel and porcine buccal mucosa than those of all borneol-free solutions. Clotrimazole-loaded ISG containing 40% borneol demonstrated appropriate physicochemical properties and rapid gel formation at microscopic and macroscopic levels. In addition, it prolonged drug release with a maximum flux of 370 µg·cm⁻² at 2 days. The borneol matrix generated from this ISG obsentively controlled the drug penetration through the porcine buccal membrane. Most clotrimazole amounts still remained in formulation at the donor part and then the buccal membrane and receiving medium, repectively. Therefore, the borneol matrix extended the drug release and penetration through the buccal membrane efficiently. Some accumulated clotrimazole in tissue should exhibit its potential antifugal activity against microbes invading the host tissue. The other predominant drug release into the saliva of the oral cavity should influence the pathogen of oropharyngeal candidiasis. Clotrimazole-loaded ISG demonstrated efficacious inhibition of growth against S. aureus, E. coli, C. albicans, C. krusei, C. Lusitaniae, and C. tropicalis. Consequently, the clotrimazole-loaded ISG exhibited great potential as a drug delivery system for oropharyngeal candidiasis treatment by localized spraying. Full article

Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments. Full article

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings. Full article

The study aimed to investigate the causative species, antifungal susceptibility, and factors associated with oropharyngeal candidiasis (OPC) among Egyptian COVID-19 patients. This is an observational, case-controlled, single-center study that included three groups: COVID-19 patients (30), COVID-19 patients with OPC (39), and healthy individuals (31). Patients’ demographic data (age, sex), laboratory tests, comorbidities, treatment, and outcomes were included. Candida species were isolated from COVID-OPC patient’s oropharyngeal swabs by convenient microbiological methods. Isolated strains were tested for antimicrobial susceptibility, biofilm production, aspartyl protease, and phospholipase activities. The most common respiratory symptoms reported were dyspnea (36/39; 92.4%) and cough (33/39; 84.7%). Candida albicans was the most common isolated species, accounting for 74.36% (29/39), followed by Candida tropicalis and Candida glabrata (15.38% and 10.26%, respectively). Amphotericin was effective against all isolates, while fluconazole was effective against 61.5%. A total of 53.8% of the isolates were biofilm producers. The phospholipase activity of C. albicans was detected among 58.6% (17/29) of the isolates. Significant variables from this study were used to create two equations from a regression model that can predict the severity of disease course and liability to fungal infection, with a stativity of 87% and 91%, respectively. According to our findings, COVID-19 patients with moderate to severe infection under prolonged use of broad-spectrum antibiotics and corticosteroids should be considered a high-risk group for developing OPC, and prophylactic measures are recommended to be included in the treatment protocols. In addition, due to the increased rate of fluconazole resistance, other new antifungals should be considered. Full article

HIV and AIDS patients are susceptible to opportunistic infections. Oral candidiasis or thrush is the primary manifestation of fungal infection in these patients. The primary objective of this literature review was to summarize established and novel treatment options for oropharyngeal fungal infections in HIV/AIDS patients. Azoles and polyenes are the two primary antifungal drug classes employed for the treatment of oral candidiasis. A literature review was conducted on Medline and Google Scholar in October of 2021 using the keywords “Oral”, “Fungal”, “HIV”, and “Treatment”. Included studies were clinical trials, meta-analyses, and randomized controlled trials. Nineteen studies regarding azoles, polyenes, and novel treatments for oropharyngeal fungal infections in HIV/AIDS patients were examined in this review. The primary concern demonstrated from these studies is increased reports of resistance to antifungals, especially development of fluconazole resistance. Additionally, studies demonstrated that fluconazole had different relapse durations comparative to other medications, and that posaconazole could possibly act as an alternate form of treatment. Nystatin was indicated as a first-line therapy for thrush in multiple studies but could be upstaged by miconazole nitrate in resource-poor settings. Amphotericin B was an effective treatment option and was shown to be resilient in terms of fungal resistance, however potent adverse side effects were reported. Alternative treatments, such as immunoglobulin antibodies and lemon grass, revealed promising antifungal effects for immunocompromised individuals. Taken together, this review provides a thorough summary of treatment options of oropharyngeal fungal infections in HIV/AIDS patients. Full article

Fungal infections caused by Candida albicans are a serious problem for immunocompromised individuals, including those undergoing radiotherapy for head and neck cancers. Targeted irradiation causes inflammatory dysregulation and damage to the oral mucosa that can be exacerbated by candidiasis. Post-irradiation the cytokine interleukin-17 (IL-17) protects the oral mucosae by promoting oral epithelial regeneration and balancing the oral immune cell populations, which leads to the eventual healing of the tissue. IL-17 signaling is also critical for the antifungal response during oropharyngeal candidiasis (OPC). Yet, the benefit of IL-17 during other forms of candidiasis, such as vulvovaginal candidiasis, is not straightforward. Therefore, it was important to determine the role of IL-17 during OPC associated with radiation-induced inflammatory damage. To answer this question, we exposed Il17ra^−/− and wild-type mice to head-neck irradiation (HNI) and OPC to determine if the IL-17 signaling pathway was still protective against C. albicans. HNI increased susceptibility to OPC, and in Il17ra^−/− mice, the mucosal damage and fungal burden were elevated compared to control mice. Intriguingly, neutrophil influx was increased in Il17ra^−/− mice, yet these cells had reduced capacity to phagocytose C. albicans and failed to clear OPC compared to immunocompetent mice. These findings suggest that radiotherapy not only causes physical damage to the oral cavity but also skews immune mediators, leading to increased susceptibility to oropharyngeal candidiasis. Full article

The objective of the study was to compare the efficacy and safety of antifungal agents used in the prevention of oropharyngeal candidiasis among HIV-infected adults. A systematic search was conducted in four databases (MEDLINE, Scopus, CENTRAL, and Embase) for eligible randomized control trials (RCTs). The network meta-analyses (NMA) were performed using a random-effects model. Interventions were ranked based on the efficacy and safety using the surface under the cumulative ranking curve (SUCRA). The quality of evidence was assessed using the GRADE approach. From a total of 1574 studies screened, 7 RCTs comprising 959 participants were included in NMA. The use of fluconazole as a prophylactic agent was associated with a significant reduction in incidence of OPC compared to placebo (RR, 0.45 (95% CI: 0.27–0.77)) in HIV-infected adults. The overall quality of evidence was graded as moderate. Fluconazole was ranked the best antifungal for efficacy (SUCRA—95.6%) as well as safety (SUCRA—39.3%) in HIV-infected adults. Overall, the quality of evidence was graded as moderate. Fluconazole can be considered as an effective agent with a better safety profile for the prophylaxis of OPC in HIV-infected adults. However, similar to any other antimicrobial agent, the risk of possibility of resistance must be weighed against the benefits. Full article

The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL and Scopus) to identify randomized controlled trials (RCTs) that evaluated the efficacy of antifungal agents in HIV patients with OPC. A network meta-analysis was performed from the data extracted from the selected studies. The agents were ranked according using surface under the cumulative ranking (SUCRA). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of evidence. A total of 15 trials were included in the quantitative analysis involving the data from a total of 2883 participants. Fluconazole was ranked as the most effective antifungal agent to achieve clinical cure (SUCRA = 0.87) in OPC followed by posaconazole and itraconazole. Posaconazole was ranked the most efficacious agent in achieving mycological cure (SUCRA = 0.81), followed by fluconazole. While nystatin was ranked the safest, the effect estimates of none of the other systemic antifungal agents were significantly higher than fluconazole. Based on the available evidence, fluconazole can be considered as the most effective drug in the treatment of OPC among HIV-infected adults and has a favorable safety profile, followed by posaconazole. Full article

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis. Full article

Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals’ skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida’s normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida’s virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia–invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis. Full article

Candida albicans is an opportunistic pathogenic fungus considered to be a common member of the human microflora. Similar to some other opportunistic microbes, C. albicans can invade and benefit from its host when the immune status of that host is weakened. Most often this happens to immunocompromised individuals, leading to the infection of oral and vaginal mucosae or the systemic spread of the pathogen throughout the entire body. Oropharyngeal candidiasis (OPC) occurs in up to 90 percent of patients with acquired immunodeficiency syndrome (AIDS), making it the most frequent opportunistic infection for this group. Upon first signs of fungal invasion, a range of host signaling activates in order to eliminate the threat. Epithelial and myeloid type cells detect C. albicans mainly through receptor tyrosine kinases and pattern-recognition receptors. This review provides an overview of downstream signaling resulting in an adequate immune response through the activation of various transcription factors. The study discusses recent advances in research of the interleukin-17 (IL-17) producing innate cells, including natural T helper 17 (nTh17) cells, γδ T cells, invariant natural killer T (iNKT) cells and type 3 innate lymphoid cells (ILC3) that are involved in response to oral C. albicans infections. Full article