Salivary proteins modulate Candida albicans virulence and may prevent oropharingeal candidiasis.

Oral candidiasis can be presented in different ways due to the virulence factors of its etiology such as Candida albicans that have developed an effective set of these factors that are able to improve its pathogenesis. The role of salivary immunological components in the development of candidiasis can provide insights for the development of new methodologies aiming to control this disease. The aim of this study was to evaluate the antifungal activity of two salivary components, histatin 5 and lactoferrin on C. albicans viability and virulence using a fluconazole resistant C. albicans clinical strain. Results showed that histatin 5 and lactoferrin decreased cell viability, and the cell surface hydrophobicity was increased by 18% in presence of 151 µg/mL of histatin 5 but was not altered by lactoferrin. It was observed the reduction of 69.3% in the expression of mannoproteins on C. albicans surface in the presence of 151 µg/mL of histatin, but proteolytic activity of serine proteinases was not inhibited by any of the proteins. Histatin 5 altered cell ultrastructure predominantly in the cytoplasmic compartment. However, this peptide does not interfere with mitochondrial function neither in membrane permeability of the yeasts. The association index between C. albicans and epithelial cells was increased by 51% in presence of 151 µg/mL of histatin. Results suggest that histatin 5 and lactoferrin affects viability and virulence of C. albicans at physiological levels, and the maintenance of these levels may be essential in the prevention of oropharyngeal candidiasis. Exogenous administration of these proteins may become a therapeutic alternative for resistant strains of C. albicans, circumventing toxicity issues, considering their constitutive features.

Monoterpene antifungal activities: evaluating geraniol, citronellal, and linalool on Candida biofilm, host inflammatory responses, and structure-activity relationships.

Introduction: Despite the rising concern with fungal resistance, a myriad of molecules has yet to be explored. Geraniol, linalool, and citronellal are monoterpenes with the same molecular formula (C10H18O), however, neither the effect of these compounds on inflammatory axis induced by Candida spp. nor the antibiofilm Structure-Activity Relationship (SAR) have been well-investigated. Herein we analyzed geraniol, linalool and citronellal antifungal activity, cytotoxicity, and distinctive antibiofilm SAR, also the influence of geraniol on Candida spp induced dysregulated inflammatory axis, and in vivo toxicity. Methods: Minimal inhibitory (MIC) and fungicidal (MFC) concentrations against Candida spp were defined, followed by antibiofilm activity (CFU-colony forming unit/mL/g of dry weight). Cytotoxic activity was assessed using human monocytes (THP-1) and oral squamous cell (TR146). Geraniol was selected for further analysis based on antifungal, antibiofilm and cytotoxic results. Geraniol was tested using a dual-chamber co-culture model with TR146 cells infected with C. albicans, and THP-1 cells, used to mimic oral epithelium upon fungal infection. Expression of Candida enzymes (phospholipase-PLB and aspartyl proteases-SAP) and host inflammatory cytokines (interleukins: IL-1ß, IL-6, IL-17, IL-18, IL-10, and Tumor necrosis factor-TNF) were analyzed. Lastly, geraniol in vivo toxicity was assessed using Galleria mellonella. Results: MIC values obtained were 1.25-5 mM/mL for geraniol, 25-100 mM/mL for linalool, and 100-200 mM/mL for citronellal. Geraniol 5 and 50 mM/mL reduced yeast viability during biofilm analysis, only 500 mM/mL of linalool was effective against a 72 h biofilm and no biofilm activity was seen for citronellal. LD50 for TR146 and THP-1 were, respectively: geraniol 5.883 and 8.027 mM/mL; linalool 1.432 and 1.709 mM/mL; and citronellal 0.3006 and 0.1825 mM/mL. Geraniol was able to downregulate expression of fungal enzymes and host pro-inflammatory cytokines IL-1ß, IL-6, and IL-18. Finally, safety in vivo parameters were observed up to 20 mM/Kg. Discussion: Despite chemical similarities, geraniol presented better antifungal, antibiofilm activity, and lower cytotoxicity when compared to the other monoterpenes. It also showed low in vivo toxicity and capacity to downregulate the expression of fungal enzymes and host pro-inflammatory cytokines. Thus, it can be highlighted as a viable option for oral candidiasis treatment.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

Clinical and mycological analysis of colonization by Candida spp. in oral leukoplakia and oral lichen planus.

OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.

Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (-102.589 kJ/mol). MIC and CFM values ranged from 264.52 µM (62.5 µg/mL) to 4232.44 µM (1000 µg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.

Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections.

Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.

Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. MATERIALS AND METHODS: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis. RESULTS: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I2 = 73.271) efficacy. CONCLUSIONS: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.

Antifungal Susceptibility and Candida sp. Biofilm Production in Clinical Isolates of HIV-Positive Brazilian Patients under HAART Therapy.

The aim of the present study was to characterize biofilms formed by Candida spp. clinical isolates (n = 19), isolated from the oral mucosa of HIV-positive patients. For characterizing the biofilms formed by several Candida sp. strains, isolated from HIV-positive patients, in terms of formed biomass, matrix composition and antifungal susceptibility profile, clinical isolates (n = 19) were collected from oral mucosa and identified. The biofilm of the samples was cultured with fluconazole (1250 mg/L), voriconazole (800 mg/L), anidulafungin (2 mg/L) or amphotericin B (2 mg/L). Afterwards, the quantification of the total biomass was performed using crystal violet assay, while the proteins and carbohydrates levels were quantified in the matrix. The results showed a predominance of C. albicans, followed by C. krusei. Around 58% of the Candida spp. biofilm had susceptibility to fluconazole and voriconazole (800 mg/L), 53% to anidulafungin and 74% to amphotericin B. C. krusei presented both the lowest and the highest biofilm matrix contents in polysaccharides and proteins. The low resistance to antifungal agents reported here was probably due to the fact that none of the participants had a prolonged exposure to these antifungals. A predominance of less virulent Candida spp. strains with low or no resistance to antifungals was observed. This can be attributed to a low fungal selective pressure. This most probably happened due to a low fungal selective pressure but also due to a good adherence to HAART therapy, which guarantees a stable and stronger immune patient response.

Antimicrobial photodynamic therapy in the treatment of oral erythematous candidiasis: a controlled and randomized clinical trial.

OBJECTIVE: To analyze the clinical and microbiological efficacy of antimicrobial photodynamic therapy (aPDT) in patients with erythematous candidiasis (EC). METHODS: This study was a controlled and randomized clinical trial in patients diagnosed with EC, who were allocated into a control group (CG) and experimental group (EG) treated with nystatin oral suspension and aPDT with methylene blue 0.1%, respectively. A clinical index was used to classify the EC lesions from mild to severe and assess the treatment efficacy. Microbiological samples were collected before and after aPDT session and analyzed by counting colony-forming units (CFUs) of Candida and Staphylococcus sp. RESULTS: A total of 41 patients (CG (n = 18); EG (n = 23)) were analyzed in our research. Of these, 16 (94.1%) of the CG and 16 (84.2%) of the EG exhibited complete remission of the lesions. Regarding the degree of the lesion, it was observed that the severe lesions were more difficult to present remission, while all the mild and moderate lesions showed complete regression (p = 0.001). The microbiological analysis showed that Candida albicans and Staphylococcus sp. were the most prevalent microorganisms, and the aPDT group showed a decrease in CFUs of these microorganisms after the first aPDT session (p < 0.05). CONCLUSIONS: aPDT proved to be a clinically and microbiologically effective therapy for treating EC. TRIAL REGISTRATION: Registered at ClinicalTrials.gov; Set 12th, 2019; No. RBR-8w8599. CLINICAL RELEVANCE: aPDT is a promising alternative treatment since it presents satisfactory results and does not cause damage to oral tissues or develop resistance to the treatment.

Does Streptococcus oralis supernatant influence on the proliferation and virulence of Candida albicans?

OBJECTIVE: To evaluate the influence of Streptococcus oralis supernatant on the proliferation and virulence of Candida albicans. DESIGN: S. oralis supernatant was obtained by filtration of overnight cultures. Single or dual-species cultures of C. albicans and S. oralis were cultivated in both planktonic and biofilm-based models. Planktonic culture growth was measured, and mature biofilms formed on resin disks were collected to measure biofilm metabolic activity, total biomass, and cell counts. Hyphae formation (virulence factor) and biofilm thickness were analyzed by confocal laser scanning microscopy. Data were analyzed by a one-way ANOVA test followed by the Tukey posthoc test (α = 0.05). RESULTS: We found that S. oralis supernatant did not influence C. albicans proliferation in planktonic cultures. However, biofilms containing S. oralis supernatant showed higher cell metabolism than C. albicans monoculture biofilms and C. albicans-S. oralis dual-culture biofilms (p < 0.05). Though S. oralis supernatants did increase biofilm metabolic activity, they did not affect the total biomass and cell counts of C. albicans (p > 0.05). However, biofilm imaging revealed enhanced C. albicans hyphae formation in biofilms containing S. oralis supernatant compared to C. albicans monoculture biofilms. CONCLUSIONS: Secreted metabolites in S. oralis supernatant may contribute to C. albicans metabolism and virulence.

Characterization and antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes.

Aim: This study aimed to develop, characterize and analyze the antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes (Chx:ßCD). Materials & methods: Chx:ßCD were characterized by physicochemical techniques and the susceptibility of nine Candida strains was assessed. The inhibition of Candida albicans biofilm growth was evaluated in a denture material modified with the incorporation of Chx:ßCD. Results: Chx was better complexed in 1:2 molar ratio by freeze-drying. Chx:ßCD presented antifungal activity against all Candida strains. When incorporated into the denture material, Chx:ßCD showed better antifungal activity, as it required about 7.5% of Chx concentration compared with the raw Chx for 14 days. Conclusion: The improved characteristics of Chx:ßCD can result in new formulations to treat oral candidiasis and denture stomatitis.

Many people who wear dentures can get a fungal infection called denture stomatitis. Treating this infection is hard because it often comes back. There are many reasons why it can come back, like not following instructions, taking the wrong amount of medicine or having a bad reaction to the drugs. Using old and poorly fitting dentures and the difficulty to maintain the medicine in the right place can also make it harder to get better. One idea to make treatment easier is to add stronger drugs with fewer side effects to the material used to make dentures. That way, patients would only need to wear dentures with the right amount of medicine for a certain time to treat the infection.

Palliative oral care in terminal cancer patients: Integrated review.

BACKGROUND: Palliative care (PC) aims to improve quality of life in patients and its families against life threatening diseases, through suffering's prevention and relief. It is the duty of the dental surgeon to possess the knowledge needed to treat a patient with little life span, in order to establish an adequate treatment plan for each situation. AIM: To synthesize the published evidence on oral conditions, impact, management and challenges in managing oral conditions among palliative patients. METHODS: Articles were selected from PubMed and Scopus electronic platforms, using a research strategy with diverse descriptors related to "palliative care", "cancer" and "oral health". The article's selection was done in two phases. The first one was performed by the main researcher through the reading of the abstracts. In the second phase two researchers selected eligible articles after reading in full those previous selected. Data was tabulated and analyzed, obtaining information about what is found in literature related to this subject and what is necessary to be approached in future researches about PC. RESULTS: As results, the total of 15 articles were eligible, being one a qualitative analysis, 13 (92.8%) clinical trials and one observational study. Of the 15 articles, 8 (53.4%) involved questionnaires, while the rest involved: one systematic review about oral care in a hospital environment, 2 oral exams and oral sample collection, one investigation of terminal patient's (TP) oral assessment records, 2 collection of oral samples and their respective analysis and one treatment of the observed oral complications. CONCLUSION: It can be concluded that the oral manifestations in oncologic patients in terminal stage are, oral candidiasis, dry mouth, dysphagia, dysgeusia, oral mucositis and orofacial pain. Determining a protocol for the care of these and other complications of cancer - or cancer therapy - based on scientific evidence with the latest cutting-edge research results is of fundamental importance for the multidisciplinary team that works in the care of patients in PC. To prevent complications and its needed to initial the dentist as early as possible as a multidisciplinary member. It has been suggested palliative care protocol based on the up to date literature available for some frequent oral complications in TP with cancer. Other complications in terminal patients and their treatments still need to have further studying.

Characterization of Oral Candida spp. Biofilms in Children and Adults Carriers from Eastern Europe and South America.

BACKGROUND: Candida albicans and non-Candida albicans Candida species (NCACs) are known to colonize and invade various tissues, including the oral mucosa. In this work, we aimed to characterize mature biofilms of several Candida spp. clinical isolates (n = 33) obtained from the oral mucosa of children, adults, and elders of Eastern Europe and South America. METHODS: Each strain was evaluated for its capacity to form biofilms in terms of total biomass using the crystal violet assay and for matrix components production (proteins and carbohydrates) using the BCA and phenol-sulfuric tests, respectively. The effect of different antifungals on biofilm formation was studied. RESULTS: in the children's group, a predominance of C. krusei (81%) was observed, while, among adults, the main species was C. albicans (59%). Most strains showed a reduced response to antimicrobial drugs when in biofilm form (p < 0.01). Moreover, it was observed that strains isolated from children produced more matrix, with higher levels of protein and polysaccharides. CONCLUSIONS: children were more likely to be infected by NCACs than adults. More importantly, these NCACs were able to form biofilms richer in matrix components. This finding is of clinical importance, particularly in pediatric care, since stronger biofilms are highly associated with antimicrobial resistance, recurrent infections, and higher therapeutic failure.

Effectiveness of fluconazole as antifungal prophylaxis in cancer patients undergoing chemotherapy, radiotherapy, or immunotherapy: systematic review and meta-analysis.

This review assessed the effectiveness of fluconazole as antifungal prophylaxis on the incidence of oral fungal diseases in patients undergoing cancer treatment. The secondary outcomes evaluated were the adverse effects, discontinuation of cancer therapy due to oral fungal infection, mortality by a fungal infection, and the mean duration of antifungal prophylaxis. Twelve databases and records were searched. The RoB 2 and ROBINS I tools were used to assess the risk of bias. The relative risk (RR), risk difference, and standard mean difference (SMD) were applied with 95% confidence intervals (CI). The certainty of the evidence was determined by GRADE. Twenty-four studies were included in this systematic review. In randomized controlled trials pooling, fluconazole was a protective factor for the primary outcome (RR = 0.30; CI: 0.16, 0.55; p < 0.01, vs placebo). Compared to other antifungals, fluconazole was only more effective than the subgroup of amphotericin B and nystatin (alone or in combination) (RR = 0.19; CI: 0.09, 0.43; p < 0.01). Fluconazole was also a protective factor in non-randomized trials pooling (RR = 0.19; CI: 0.05, 0.78; p = 0.02, vs untreated). The results showed no significant differences for the secondary outcomes. The certainty of the evidence was low and very low. In conclusion, prophylactic antifungals are necessary during cancer treatment, and fluconazole was shown to be more effective in reducing oral fungal diseases only compared with the subgroup assessing amphotericin B and nystatin, administered alone or in combination.

Atividade antifúngica do óleo de melaleuca sobre a candidíase oral: revisão da literatura / Antifungal activity of melaleuca oil on oral candidiasis: literature review

A candidíase oral trata-se de uma infecção fúngica e tem como cepa predominante a Candida albicans. Este fungo é encontrado em diferentes membranas mucosas do organismo humano e quando ocorre um desequilíbrio da microbiota local, manifestam-se múltiplas lesões que podem evoluir para quadros clínicos severos. Apresenta elevada frequência em pacientes imunossuprimidos e sob uso prolongado de antibióticos e corticosteroides, e o seu tratamento padrão se baseia na utilização de compostos azóis e poliênicos. Contudo, devido à possível citoxicidade desses medicamentos associada à resistência dos microrganismos, há uma crescente busca por terapias alternativas, o que inclui o uso de fitoterápicos. O presente estudo objetivou apresentar a utilização do óleo essencial de melaleuca ou Tea Tree Oil (TTO) no manejo de infecções fúngicas em cavidade oral. A metodologia se baseou na busca inicial de artigos nas bases eletrônicas: National Library of Medicine (PubMed), Biblioteca Virtual em Saúde (BVS) e literatura cinzenta do Google Scholar, utilizando-se o cruzamento dos descritores DeCS/MeSH "melaleuca oil" AND "oral thrush". De forma a complementar a fundamentação teórica, utilizou-se sites institucionais, além da livre busca através das referências inicalmente selecionadas. Um total de 20 trabalhos foram incluídos e os resultados demonstraram efeito satisfatório do óleo de TTO na prevenção e no tratamento da candidíase oral em cepas de Candida albicans através de estudos experimentais em modelo animal. O TTO se mostrou eficaz no manejo da candidíase oral em animais, todavia, são necessários ensaios clínicos controlados para obtenção de posologias eficazes e seguras para o paciente.

Oral candidiasis is a fungal infection and its predominant strain is Candida albicans. This fungus is found in different mucous membranes of the organism and when there is an imbalance in the local microbiota, multiple lesions are manifested that can evolve into severe clinical conditions. It has a high frequency in immunosuppressed patients and under prolonged use of antibiotics and corticosteroids, and its standard treatment is based on the use of azole and polyene compounds. However, due to the possible cytotoxicity of these drugs associated with the resistance of microorganisms, there is a growing search for alternative therapies, which includes the use of herbal medicines. The present study aimed to present the use of tea tree essential oil or Tea Tree Oil (TTO) in the management of fungal infections in the oral cavity. The methodology was based on the initial search for articles in electronic databases: National Library of Medicine (PubMed), Virtual Health Library (BVS) and Google Scholar gray literature, using the crossing of the DeCS/MeSH descriptors "melaleuca oil" AND "oral thrush". In order to complement the theoretical foundation, institutional sites were used, in addition to the free search through the initially selected references. A total of 20 studies were included and the results demonstrated a satisfactory effect of TTO oil in the prevention and treatment of oral candidiasis in strains of Candida albicans with experimental studies in animal models. TTO proved to be effective in the management of oral candidiasis in animals, however, controlled clinical trials are needed to obtain effective and safe dosages for the patient.

Candida-associated denture stomatitis: clinical, epidemiological, and microbiological features.

OBJECTIVE: The identification of Candida spp. in denture stomatitis, the clinical manifestations, and the antifungal susceptibility profile lead to a correct and individualized therapeutic management of the patients. This study is aimed at investigating the clinical manifestations and epidemiological and microbiological characteristics of Candida-associated denture stomatitis. DESIGN: The samples were obtained by swabbing the oral mucosa of the subjects and then seeded onto Sabouraud Dextrose Agar and onto CHROMagar® Candida plates. The identification at the species level was confirmed by Matrix Assisted Laser Desorption Time of Flight Mass Spectrometry. Clinical classification was performed according to the criteria proposed by Newton (1962): (i) pinpoint hyperemia, (ii) diffuse hyperemia, and (iii) granular hyperemia. For carrying out the antifungal susceptibility testing, we adopted the CLSI M27-S4 protocol. RESULTS: C. albicans was the most prevalent species in our study. Regarding non-albicans Candida species, C. glabrata was the most common species isolated from the oral mucosa (n = 4, 14.8%), while in the prosthesis, it was C. tropicalis (n = 4, 14.8%). The most prevalent clinical manifestation was pinpoint hyperemia and diffuse hyperemia. Candida albicans, C. glabrata, and C. parapsilosis were susceptible to all the tested antifungals. Concerning fluconazole and micafungin, only two strains showed dose-dependent sensitivity (minimum inhibitory concentration (MIC), 1 µg/mL) and intermediate sensitivity (MIC, 0.25 µg/mL). One C. tropicalis strain was resistant to voriconazole (MIC, 8 µg/mL). CONCLUSIONS: C. albicans was the most common species found in oral mucosa and prosthesis. The tested antifungal drugs showed great activity against most isolates. The most prevalent clinical manifestations were Newton's type I and type II.

Evaluation of oral mucositis, candidiasis, and quality of life in patients with head and neck cancer treated with a hypofractionated or conventional radiotherapy protocol: a longitudinal, prospective, observational study.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection. METHODS: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks. PURPOSE: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT. RESULTS: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen. CONCLUSIONS: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments.

Diversidad de especies de Candida recuperadas de la cavidad bucal de pacientes oncológicos en Barranquilla, Colombia Candida spp bucal y cáncer / Species diversity of the genus Candida in the oral cavity of cancer patients in Barranquilla, Colombia

Resumen Se caracterizaron especies de Candida recuperadas de la cavidad bucal de pacientes oncológicos en una institución prestadora de salud de Barranquilla, Colombia. La investigación tuvo un diseño de corte transversal, mediante un muestreo a conveniencia se seleccionaron 60 pacientes oncológicos con candidiasis oral. Las muestras obtenidas se cultivaron en agar Sabouraud cloranfenicol, CHROMagar® Candida y agar Sabouraud dextrosa. Los microorganismos aislados se identificaron y se estableció el perfil de sensibilidad a los antifúngicos. Se aplicó estadística descriptiva, prueba de X 2 y análisis bivariado utilizando el programa Statgraphics Centurión XVII, con razón de momios (OR) para probabilidad de ocurrencia. Se identificaron un total de 107 cepas de Candida correspondientes a 15 especies, distribuidas del siguiente modo: C. albicans 23%, C. glabrata 18%, C. tropicalis 13%, C. krusei 10%, C. intermedia y C. lipolytica con 1,5%. En 77% de los casos estuvieron implicadas especies diferentes de C. albicans. Se identificó la existencia de relación entre cáncer del sistema reproductor y C. guilliermondii (p = 0,0001, < 0,05; OR 17) y entre C. colliculosa y cánceres respiratorios (p = 0,0003 < 0,05; OR 19,5). El 99% de las especies de Candida identificadas fueron sensibles a los antifúngicos: fluconazol, voriconazol, caspofungina y micafungina. Solo una cepa de C. krusei fue resistente. Se concluye que existió diversidad de especies de Candida en la cavidad bucal de pacientes oncológicos, ya sea como colonizantes únicos o en combinación, de modo que más de una especie de Candida podría ser responsable de la infección micótica en la cavidad bucal de estos enfermos.

Abstract Candida spp. was characterized in the oral cavity of cancer patients in a health care center in Barranquilla, Colombia. This is a cross-sectional investigation including 60 oncological patients with oral candidiasis, selected by convenience sampling, from whom samples were subjected to culture in Sabouraud chloramphenicol agar, CHROMagar® Candida and Sabouraud dextrose agar were taken. The antifungal susceptibility profile was then identified and established. Descriptive statistics, Chi square test, and bivariate analysis were conducted using the Statgraphics Centurion XVII software with odds ratio (OR) for the probability of occurrence. A total of 107 Candida strains were identified belonging to 15 species, C. albicans with 23%, C. glabrata with 18%, C. tropicalis 13%, C. krusei 10%, C intermedia, and C. lipolytica with 1.5%. Species other than C. albicans were identified in 77% of the cases. A relationship between reproductive system cancer and C. guilliermondii was identified (p = 0.0001, <0.05) OR: 17.0. Between C. colliculosa and respiratory cancer (p = 0.0003, <0.05) OR 19.5. With regard to antifungal susceptibility, 99% of the identified Candida species were susceptible to the following antifungals: fluconazole, voriconazole, caspofungin, and micafungin. Only one strain of C. krusei was resistant. It is concluded that there was a diversity of Candida species, either single or mixed in cancer patients, which could determine that only one species is not responsible for fungal infection in the oral cavity.

Species distribution and susceptibility profiles of oral candidiasis in hematological malignancy and solid tumor patients.

Oral colonization and infection by Candida species are common in cancer patients receiving chemoradiotherapy, which has significantly increased in recent years. This study aimed to evaluate the frequency, distribution, and antifungal susceptibility profiles of Candida species isolates in patients with hematological malignancy and solid tumors. This study was conducted on a total of 45 cancer patients undergoing treatment with concurrent chemoradiotherapy within 2019-2020. The identification of Candida species was accomplished based on conventional examination and molecular assays. The minimum inhibitory concentrations were determined based on the guidelines of Clinical and Laboratory Standards Institute. The highest prevalence rates of oral candidiasis were observed in patients with chronic lymphoid leukemia (24.4%) and lymphoma (20%). The majority of the patients had oral candidiasis caused by non-albicans Candida species (64.4%). The results of the multiplex PCR for the identification of Candida glabrata, Candida nivariensis, Candida bracarensis, and species-specific Candida parapsilosis complex showed that all isolate amplification products at 397 bp and 171 bp were related to C. glabrata and C. parapsilosis, respectively. There was a significant difference in the Candida species distribution between the hematological malignancies and solid tumors patients. The results of MIC showed that clotrimazole, voriconazole, and caspofungin were the most effective antifungal drugs against oral non-Candida albicans isolates. An understanding of the epidemiology of oral candidiasis among hematological malignancies and solid tumors patients is currently imperative to guide optimal empirical treatment strategies for affected patients.

[Species diversity of the genus Candida in the oral cavity of cancer patients in Barranquilla, Colombia]. / Diversidad de especies de Candida recuperadas de la cavidad bucal de pacientes oncológicos en Barranquilla, Colombia.

Candida spp. was characterized in the oral cavity of cancer patients in a health care center in Barranquilla, Colombia. This is a cross-sectional investigation including 60 oncological patients with oral candidiasis, selected by convenience sampling, from whom samples were subjected to culture in Sabouraud chloramphenicol agar, CHROMagar® Candida and Sabouraud dextrose agar were taken. The antifungal susceptibility profile was then identified and established. Descriptive statistics, Chi square test, and bivariate analysis were conducted using the Statgraphics Centurion XVII software with odds ratio (OR) for the probability of occurrence. A total of 107 Candida strains were identified belonging to 15 species, C. albicans with 23%, C. glabrata with 18%, C. tropicalis 13%, C. krusei 10%, C intermedia, and C. lipolytica with 1.5%. Species other than C. albicans were identified in 77% of the cases. A relationship between reproductive system cancer and C. guilliermondii was identified (p = 0.0001, <0.05) OR: 17.0. Between C. colliculosa and respiratory cancer (p = 0.0003, <0.05) OR 19.5. With regard to antifungal susceptibility, 99% of the identified Candida species were susceptible to the following antifungals: fluconazole, voriconazole, caspofungin, and micafungin. Only one strain of C. krusei was resistant. It is concluded that there was a diversity of Candida species, either single or mixed in cancer patients, which could determine that only one species is not responsible for fungal infection in the oral cavity.