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.

Anti-Candida activity and biocompatibility of silver nanoparticles associated with denture glaze: a new approach to the management of denture stomatitis.

The association of silver nanoparticles (AgNps) to sealant agent Palaseal® can be a promising alternative for complete denture wearers who may develop denture stomatitis (DS). The study aimed to evaluate the anti-Candida and biocompatible potential of silver nanoparticles synthesized by three routes associated with denture glaze to prevent and/or treat oral candidiasis. Surface acrylic resin specimens were treated with different associations of glaze with AgNps (VER+AgUV, VER+AgTurk and VER+AgGm). As controls, specimens were treated with glaze+nystatin (VER+Nyst), glaze only (VER) or submerged in PBS (PBS). Afterwards, Candida albicans biofilm was developed for 24 h, 15 d and 30 d. Subsequently, the biofilm was quantified by CFU/mL, XTT assay and confocal laser scanning microscopy. Fibroblasts were submitted to conditioned medium with the same associations for 24, 48 and 72 h and LIVE/DEAD® viability test was carried out. Regardless of the period, there was a significant reduction (p < 0.01) of viable fungal cells load, as well as inhibition of fungal metabolic activity, in specimens treated with glaze+AgNps associations, compared to VER and PBS. The anti-Candida effects of the associations were similar to the VER+Nyst group, with emphasis on VER+AgGm, which showed the highest percentage values of non-viable fungal cells maintained over time. The associations did not prove toxicity to fibroblasts. The AgNps exerted antimicrobial activity against C. albicans biofilms and are biocompatible. The most effective results were achieved with the association of glaze+silver nanoparticles synthesized by the green chemistry method (AgGm), proving to be an innovative alternative in the management of DS.

Efeitos da terapia fotodinâmica mediada por curcumina livre e associada a nanopartículas de ferro sobre Candida spp. e biofilmes de estomatite protética / Effects of curcumin-mediated photodynamic therapy, alone and combined with Iron nanoparticles, on Candida spp. and prosthetic stomatitis biofilms

A estomatite protética é uma doença oral que resulta em processo inflamatório crônico da mucosa de suporte de uma prótese dentária, frequentemente associada à infecção por Candida. O tratamento da estomatite protética é dificultado pelo desenvolvimento de resistência das cepas de Candida aos fármacos antifúngicos. Neste cenário, este estudo teve como objetivo avaliar o efeito da terapia fotodinâmica antimicrobiana (TFDa) mediada por curcumina livre (CUR) e nanopartículas de ferro revestidas de curcumina (NpFeCUR) sobre Candida spp. Para isso, o estudo foi dividido em 2 etapas. Na etapa 1, os efeitos da TFDa mediada por NpFeCUR foi estudado sobre células planctônicas e biofilmes monoespécie da cepa de C. albicans SC5314. Após o tratamento com TFDa, as células viáveis foram quantificadas por contagem de Unidades Formadoras de Colônias (UFC). Os resultados dessa etapa demonstraram que a TFDa mediada por NpFeCUR não foi capaz de reduzir a viabilidade fúngica em culturas planctônicas e em biofilmes. Na etapa 2, foi avaliado o efeito da TFDa mediada por CUR sobre biofilmes formados a partir de amostras clínicas de estomatite protética. Essas amostras foram coletadas de 5 pacientes com estomatite protética e analisadas quanto à presença de Candida spp. pelo método de Gram e semeadura em Chromagar Candida. As espécies de Candida foram identificadas por meio de espectrometria de massa (MALDI-TOF). A seguir, a TFDa foi testada sobre biofilmes monoespécies das espécies de Candida isoladas e sobre os biofilmes microcosmos. Após a TFDa, as células viáveis foram determinadas pela contagem de UFC em meios de cultura não seletivo e seletivos para leveduras, estreptococos, estafilococos e estreptococos do grupo mutans. Nos resultados da etapa 2, foi encontrada a presença de Candida nas amostras clínicas de 3 pacientes (P1, P2 e P3). Nas amostras P1 e P3, foi identificada a espécie C. dubliniensis, já na amostra P2 foi encontrada C. albicans. Os biofilmes monoespécies dessas cepas apresentaram redução em torno de 3,0 log10 UFC após o tratamento com TFDa. Para os biofilmes microcosmos, a redução do número de UFC causada pela TFDa variou entre as amostras dos pacientes e os meios de cultura, sendo capaz de inibir o crescimento de microrganismos totais, leveduras, estreptococos, estreptococos do grupo mutans e estafilococos. Conclui-se que a TFDa mediada por NpFeCUR não apresentou atividade antifúngica contra C. albicans. Já a TFDa mediada por CUR foi eficaz na redução das espécies de Candida e biofilmes provenientes de lesões de estomatite protética.(AU)

Prosthetic stomatitis is an oral disease that results in a chronic inflammatory process of the supporting mucosa of a dental prosthesis, often associated with Candida infection. The treatment of prosthetic stomatitis is complicated by the development of resistance in Candida strains to antifungal drugs. In this scenario, this study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) mediated by free curcumin (CUR) and curcumin-coated iron nanoparticles (FeCUR NPs) on Candida spp. For this purpose, the study was divided into 2 stages. In stage 1, the effects of aPDT mediated by FeCUR NPs were studied on planktonic cells and monospecies biofilms of the C. albicans SC5314 strain. After aPDT treatment, viable cells were quantified by Colony-Forming Units (CFU) counting. The results of this stage demonstrated that aPDT mediated by FeCUR NPs was unable to reduce fungal viability in planktonic cultures and biofilms. In stage 2, the effect of aPDT mediated by CUR on biofilms formed from clinical samples of prosthetic stomatitis was evaluated. These samples were collected from 5 patients with prosthetic stomatitis and analyzed for the presence of Candida spp. by Gram staining and seeding on Chromagar Candida. Candida species were identified using mass spectrometry (MALDI-TOF). Subsequently, aPDT was tested on monospecies biofilms of the isolated Candida species and on microcosm biofilms. After aPDT, viable cells were determined by CFU counting on non-selective and selective culture media for yeasts, streptococci, staphylococci, and mutans group streptococci. In the results of stage 2, Candida was found in clinical samples from 3 patients (P1, P2, and P3). In P1 and P3 samples, C. dubliniensis was identified, while C. albicans was found in the P2 sample. Monospecies biofilms of these strains showed a reduction of around 3.0 log10 CFU after aPDT treatment. For microcosm biofilms, the reduction in CFU caused by aPDT varied between patient samples and culture media, being able to inhibit the growth of total microorganisms, yeasts, streptococci, mutans group streptococci, and staphylococci. It is concluded that aPDT mediated by FeCUR NPs did not exhibit antifungal activity against C. albicans. On the other hand, aPDT mediated by CUR was effective in reducing Candida species and biofilms from prosthetic stomatitis lesions.(AU)

Atividade antifúngica de nanofibras de policaprolactona/nistatina: estudo in vitro e in vivo / Antifungal activity of polycaprolactone/nystatin nanofibers: in vitro and in vivo study

Este estudo avaliou a eficácia in vitro e in vivo de mantas de nanofibras (NF) de policaprolactona (PCL) incorporadas com nistatina (NIS) no tratamento da estomatite protética (EP) em modelos animais. NF foram sintetizadas com diferentes concentrações de NIS, totalizando quatro soluções: PCL puro, PCL/NIS 0,045 g, PCL/NIS 0,090 g e PCL/NIS 0,225 g. A liberação da NIS foi analisada por espectroscopia Ultravioleta-Visível. A capacidade das mantas de inibirem o biofilme de Candida albicans, principal fator etiológico da EP, dividindo-se cinco grupos (N=5) compostos por um grupo com controle de células de C. albicans e com PCL puro, além das três concentrações de NIS. A seguir, foi analisada a viabilidade celular em queratinócitos humanos (HaCat) por meio do teste colorimétrico de resazurina. Cinco grupos foram divididos (N=10): controle celular, PCL puro e as três concentrações de NIS. Em modelos animais de ratos Wistar albinos (N=18), dispositivos palatinos (DP) de resina acrílica foram confeccionados simulando próteses totais e utilizados para a indução da EP. Para isso, DP contaminados com C. albicans foram cimentados na região molar da cavidade bucal dos animais e permaneceram em boca por 48 h. Após esse período, os DP foram removidos e os animais foram divididos em três grupos: (C) controle; (B1) com tratamento por mantas de PCL/NIS 0,045 g e (B2) PCL/NIS 0,225 g, com N=6. Então novos DP, livres de contaminação, foram cimentados na cavidade oral dos animais e permaneceu por mais 48 h. Após esse período, os animais foram eutanasiados, a contagem de UFC/ mL foi realizada e os palatos foram coletados para a análise histológica. A curva padrão de NIS obtida apresentou R2 de 0,99. As três concentrações de NF apresentaram liberação de NIS, com pico no tempo de 6 h e valores de 66,26 µg/ mL para PCL/NIS 0,045 g, de 333,87 µg/ mL para PCL/NIS 0,090 g e 436,51 µg/ mL para PCL/NIS 0,225 g, constantes até o fim do experimento. Os grupos com NIS reduziram em 2,5 log10 de crescimento do biofilme fúngico em relação aos grupos sem tratamento, Controle e PCL, sem diferença estatística significativa. Não foi observada citotoxicidade nas células HaCat, com viabilidade celular de 93,7% para PCL/NIS 0,045 g, 72,6% para PCL/NIS 0,090 g e 72,4% para PCL/NIS 0,225 g. A indução da EP nos três grupos foi possível e, porém, sem redução significativa na contagem de UFC/ mL de C. albicans nos grupos B1 e B2. Na análise histológica do grupo C pôde-se observar infiltração de hifas de Candida na camada queratinizada, presença de células inflamatórias formando micro abscessos e um discreto infiltrado inflamatório no tecido conjuntivo subjacente ao epitélio infectado. Nos grupos B1 e B2 não foram encontradas alterações epiteliais, concluindo-se que as NF demonstraram atividade antifúngica in vitro e foram efetivas na prevenção da penetração de hifas no tecido palatino de animais com DP (AU)

This study evaluated the in vitro and in vivo efficacy of nanofiber (NF) mats of polycaprolactone (PCL) incorporated with nystatin (NIS) in the treatment of denture stomatitis (DS) in animal models. NFs were synthesized with different concentrations of NIS, totaling four solutions: pure PCL, PCL/NIS 0.045 g, PCL/NIS 0.090 g, and PCL/NIS 0.225 g. The release of NIS was analyzed by Ultraviolet-Visible spectroscopy. The ability of the mats to inhibit Candida albicans biofilm, the main etiological factor of DS, was assessed by dividing five groups (N=5) composed of a group with C. albicans cell control and with pure PCL, in addition to the three concentrations of NIS. Next, cell viability in human keratinocytes (HaCat) was analyzed using the resazurin colorimetric test. Five groups were divided (N=10): cell control, pure PCL, and the three concentrations of NIS. In albino Wistar rat animal models (N=18), palatal devices (PD) made of acrylic resin were fabricated to simulate total prostheses and used to induce DS. For this, PD contaminated with C. albicans were cemented in the molar region of the animals' oral cavity and remained in the mouth for 48 hours. After this period, the PDs were removed, and the animals were divided into three groups: (C) control; (B1) treated with PCL/NIS 0.045 g mats, and (B2) PCL/NIS 0.225 g, with N=6. Then new, uncontaminated PDs were cemented in the animals' oral cavity and remained for another 48 hours. After this period, the animals were euthanized, UFC/ mL counts were performed, and the palates were collected for histological analysis. The standard NIS curve obtained showed an R2 of 0.99. The three concentrations of NF showed NIS release, with a peak at 6 h and values of 66.26 µg/ mL for PCL/NIS 0.045 g, 333.87 µg/ mL for PCL/NIS 0.090 g, and 436.51 µg/ mL for PCL/NIS 0.225 g, remaining constant until the end of the experiment. The groups with NIS reduced fungal biofilm growth by 2.5 log10 compared to the untreated groups, Control and PCL, with no significant statistical difference. No cytotoxicity was observed in HaCat cells, with cell viability of 93.7% for PCL/NIS 0.045 g, 72.6% for PCL/NIS 0.090 g, and 72.4% for PCL/NIS 0.225 g. Induction of DS in the three groups was possible; however, there was no significant reduction in UFC/ mL counts of C. albicans in groups B1 and B2. Histological analysis of group C revealed infiltration of Candida hyphae in the keratinized layer, presence of inflammatory cells forming micro abscesses, and a discreet inflammatory infiltrate in the connective tissue underlying the infected epithelium. No epithelial alterations were found in groups B1 and B2, concluding that NFs demonstrated in vitro antifungal activity and were effective in preventing hyphal penetration into palatal tissue in animals with PD.(AU)

Can 0.5% Sodium Hypochlorite Treat Candida-Associated Denture Stomatitis?

ABSTRACT Objective: To evaluate a 0.5% sodium hypochlorite (SH) protocol in reducing Candida spp. levels in complete dentures (CD) and palate and denture stomatitis (DS) remission. Material and Methods: Twelve CD wearers diagnosed with Candida-associated denture stomatitis (CADS) had their initial situation (Candida spp. levels and DS score) recorded (baseline). Then, participants were instructed to soak dentures once a day (10 minutes) in 0.5% SH. Candida spp. levels and DS scores were reassessed after 15, 30, and 60 days of SH denture cleanness. Biofilms from the denture base and palate were seeded in CHROMagar Candida. After incubation, colony-forming units were calculated. The palate was photographed at each time point, and DS was assessed according to Newton's classification. Data of Candida spp. levels were analyzed by 2-way repeated measures ANOVA followed by the Holm-Sidak test, and DS scores data were accessed by Friedman's 2-way ANOVA by ranks (α=0.05). Results: 0.5% SH significantly reduced Candida spp. levels after treatment compared to baseline (p<0.001) for both sites. Although at baseline, Candida spp. counts were higher on the denture base (p<0.001), no significant differences were observed between the collected areas within the other time points (p<0.05). Also, 0.5% SH effectively reduced clinical signs of DS after treatment (p<0.05). Conclusion: The protocol tested effectively decreased Candida spp. levels on the denture base and palatal mucosa and effectively reduced the signs of DS.

Relation between the risk factors for the severity of denture stomatitis and quality of life of complete edentulous individuals: a cross-sectional study.

OBJECTIVE: To assess the association between risk factors for developing denture stomatitis (DS) and oral health-related quality of life (OHRQoL) in complete denture wearers. METHODOLOGY: Participants of both sexes, wearing complete dentures, were classified using the modified Newton classification for the absence or the severity of DS and allocated to groups Normal or zero, IA, IB, II, and III. Lifestyle, oral and denture history, and medication use were assessed using specific questionnaires; clinical parameters such as anatomical characteristics of support were evaluated with the Kapur classification; salivary flow (SF) was calculated by the volume of unstimulated saliva per minute; and microbial load was determined by counting colony forming units (CFU) of target microorganisms present in the biofilm collected from dentures and palate. OHIP-EDENT assessed the OHRQoL. Kendall's tau_b and Spearman tests were applied with a significance level of 5%. RESULTS: 184 patients (143 female and 41 male) aged 65.5 ± 6.8 years were evaluated. Positive correlations were found for sex (women; p=0.013, r=0.16), individuals who started to consume alcoholic beverages as a young adult (18-27 years) (p=0.008, r=0.22), CFU of Candida spp. (p<0.001, r=0.27 denture; p<0.001, r=0.31 palate); Candida albicans (p=0.004, r=0.22 denture; p=0.003, r=0.25 palate), and Candida glabrata (p=0.004, r=0.22 denture; p=0.001, r=0.27 palate). Moreover, negative correlations with DS were found for CFU of Staphylococcus spp. (p=0.004, r=-0.20 palate) and enterobacteria (p=0.002, r=-0.24 palate), as well as a negative correlation between SF (p=0.009, r=-0.193) and DS. The CFU of Staphylococcus spp. and enterobacteria on the palate significantly correlated with OHRQoL. CONCLUSION: Being female, consuming alcoholic beverages as a young adult, CFU of Candida spp., Candida albicans, Candida glabrata, and salivary flow may be the most significant risk factors for DS. The microbial load of Staphylococcus spp. and enterobacteria seems to influence the quality of life for complete denture wearers.

Medium-chain fatty acids as an alternative treatment for denture stomatitis in older people.

OBJECTIVE: To determine the effect of medium-chain fatty acids (MCFA) on the severity of denture stomatitis (DS) and the counts of Candida spp. in older people (OP) wearing removable prostheses (RP). MATERIALS AND METHODS: This randomized, controlled and triple-blind study included forty-three OP presenting DS. The control group was treated with 0.12% chlorhexidine (CHX) and the experimental group with MCFA, 2 × /day for 15 days. Intraoral examination and counts of Candida spp. were performed at 0, 7, and 15 days. The differences between both groups in the decrease of the severity of DS and the viability of Candida spp. were determined clinically and microbiologically, respectively. RESULTS: OP carriers of RP treated with MCFA presented remission of the clinical signs of DS, but the Candida spp. counts only decreased significantly in the CHX-treated group at 7 days of treatment (p < 0.05). Besides, MCFA was shown to reduce the clinical signs of DS after the first week of application, while CHX after the second week. CONCLUSIONS: The MCFA is effective in reducing the clinical signs of DS associated with oral candidiasis in subjects with RP. Both treatments showed a significant decrease in severity, for MCFA after the first week and for CHX two weeks after starting the corresponding treatment. CLINICAL RELEVANCE: The MCFA is an effective, harmless, and accessible treatment alternative against DS, since it manages to reduce the severity of the lesion in the milder cases of DS in the oral mucosa of OP carriers of RP.

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.

Characterization, Antifungal Evaluation against Candida spp. Strains and Application of Nystatin: ß-cyclodextrin Inclusion Complexes.

BACKGROUND: Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug, according to the Biopharmaceutical Classification System, that possesses limited bioavailability and is used for local activity. OBJECTIVE: This study developed and characterized nystatin:ß-cyclodextrin (Nys:ßCD) inclusion complexes and evaluated their activity against Candida spp. METHODS: Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. guilliermondii, C. tropicalis, and C. auris was assessed using the broth microdilution method. The applicability of Nys:ßCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment. RESULTS: Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:ßCD complex presents antifungal activity against all evaluated Candida strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys. CONCLUSION: This work represents a significant contribution to treating a wide variety of diseases caused by the Candida species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.

Natural products for the treatment of denture stomatitis: A systematic review.

STATEMENT OF PROBLEM: Evidence for the efficacy and safety of natural products for the treatment of denture stomatitis is lacking. PURPOSE: The purpose of this systematic review was to answer the question "Are topical natural substances effective and safe compared with conventional antifungals in the treatment of denture stomatitis?" MATERIAL AND METHODS: A structured search in 11 databases, including non-peer-reviewed, was undertaken. Two authors independently selected the studies, extracted the data, assessed the study quality, and graded the evidence, with disagreement resolved with a third reviewer. Data were evaluated descriptively by following Synthesis Without Meta-analysis (SWiM) reporting items. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020216213. RESULTS: After the removal of duplicates, 1925 records remained, and after a 2-phase reading of abstracts and full texts, 17 studies were included. Propolis, green tea, ginger, Zataria multiflora, chitosan, garlic, Artemisia, Schinus terebinthifolius Raddi, Uncaria tomentosa, Punica granatum, and Ricinus communis appeared to have similar efficacy and safety when compared with nystatin or miconazole. Most of the studies presented a high risk of bias. CONCLUSIONS: Certainty in the body of evidence that natural products might be appropriately used in the treatment of denture stomatitis is low. Well-designed randomized controlled trials are still needed to evaluate the topic better because there is high heterogeneity among the studies.

Photodynamic therapy in the treatment of denture stomatitis: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Photodynamic therapy is widely used in dentistry, but limited evidence exists regarding its effectiveness in treating denture stomatitis. High resistance to antifungals has been reported, and photodynamic therapy could be an alternative treatment. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether photodynamic therapy is effective in reducing denture stomatitis. MATERIAL AND METHODS: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and recorded in the prospective register of systematic reviews (PROSPERO) (CRD42020205589) to answer the population, intervention, control, outcome (PICO) question: "Is photodynamic therapy effective in the treatment of denture stomatitis when compared with the use of antifungal agents?" Electronic searches were performed in databases PubMed/MEDLINE, Cochrane library, and Web of Science for articles published until February 2021 by using the following terms: (denture stomatitis OR oral candidiasis) AND (low-level light therapy OR laser therapy OR lasers OR photodynamic therapies OR photochemotherapy) AND (antifungal drugs OR antifungal agents OR antimicrobial OR treatment). Clinical trials and randomized clinical trials, studies in the English language, and studies comparing antifungal agents with photodynamic therapy were included. RESULTS: In total, 5 articles were selected for the qualitative analysis and 3 for the meta-analysis. No significant difference was detected between antifungal therapy and photodynamic therapy in the reduction of colony-forming units on the palate. In a subgroup analysis, a significant difference was found in the reduction of colony-forming units on the palate at 15 days and at the denture surface at 30 days. CONCLUSIONS: Photodynamic therapy is effective in the treatment of denture stomatitis, but after 30 days and 15 days, the antifungals demonstrated better performance.

A novel rat model of denture stomatitis and the role of antibiotics in the development of the disease.

This study compared different conditions to establish a rat model of denture stomatitis. Immunocompetent Wistar rats were divided into two groups (n = 35): Tetracycline = administration of 0.83 mg/ml of tetracycline hydrochloride 7 days before induction of denture stomatitis and amoxicillin = administration of 0.156 mg/ml of amoxicillin with clavulanic acid 4 days before induction of denture stomatitis. A suspension of Candida albicans was inoculated on the palate followed by the use of a palatal device contaminated with C. albicans inoculum for 4 days to induce denture stomatitis. As controls, some rats were not submitted to any procedure or used a sterile palatal device for 4 days. The development of denture stomatitis was confirmed by visual analysis, colony-forming units per milliliter (CFU/ml) count, histopathological and immunohistochemical analyses, and through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats were euthanized right after device removal (T0), 4 (T4), or 6 (T6) days after device removal. Tetracycline improved the development of the disease, with more severe clinical signs at T0. Similar results were observed in the CFU/ml count and in the histometric and immunohistochemical analyses. Higher MPO expression was detected in the palates of the tetracycline group (P = .006). Despite the subtle differences between antibiotics, tetracycline showed better results in inducing and maintaining denture stomatitis for at least 4 days after device removal.

Denture stomatitis is an oral inflammatory disease with high recurrence rates. Different animal models have been reported in the literature, but some gaps still need to be addressed. A reproducible in vivo model should be established to test new treatment approaches.

Resilient liner modified by antimicrobials for denture stomatitis treatment: A randomized controlled trial.

OBJECTIVES: This randomized clinical trial evaluated the effectiveness of an interim denture resilient liner (Trusoft) modified with minimum inhibitory concentrations (MICs) of antimicrobial agents for Candida albicans biofilm in the denture stomatitis (DS) treatment. METHODS: Forty participants with DS and maxillary complete denture (MCD) wearers were randomly assigned to one of the treatments for 14 days (n=10): nystatin oral suspension (Control-100,000IU/mL; 4 × /day), MCD relined with Trusoft either without (Tru) or with nystatin (Ny) or chlorhexidine diacetate (Chx) at MICs. Cytological smears and mycological quantitative cultures were taken from the palate and denture before treatment (baseline), at the end of treatment (day 14), and at follow-up (days 30, 45, and 60). Photographs of the palate were made at each visit. Data were analyzed by the Cochran and χ2 tests, ANOVA and the Tukey test or the Friedman and Kruskal-Wallis tests (α=0.05). RESULTS: Palatal smears of the Ny and Chx groups exhibited no mycelial Candida (0%) on day 14, and, at the 60-day follow-up, it was observed for only 1 participant from Chx group. MCD smears showed reduction in mycelial forms for all groups on day 14 (P<0.05), but this difference was maintained at follow-up only for the relined dentures (P<0.05). Unlike Tru and the control groups, Ny and Chx groups evidenced a significant reduction in CFU/mL values and DS severity throughout the trial (P<0.05). CONCLUSIONS: The addition of nystatin and chlorhexidine at MICs to an interim resilient liner is a promising treatment for DS, with better results than those for conventional therapy with nystatin suspension, including the follow-ups. CLINICAL SIGNIFICANCE: Compared with conventional topical antifungal therapy, modifying a denture reline material with antimicrobials provided a therapeutic option for denture stomatitis. This non-invasive, straightforward therapeutic approach can be easily adopted by dentists and has the advantage of not requiring patient compliance while maintaining therapeutic concentrations on the denture base.

In vitro antimicrobial effects of chitosan on microcosm biofilms of oral candidiasis.

OBJECTIVE: This study assessed the effects of chitosan (CS) on microcosm biofilms derived from saliva of patients with Candida-associated denture stomatitis. METHODS: Five removable denture wearers with denture stomatitis were included in the study. The minimum inhibitory concentration (MIC) of CS against clinical isolates of Candida albicans was determined according to the broth microdilution method. Pooled saliva from the donors was used as an inoculum for the formation of biofilms, which were developed during 72 h on acrylic surfaces in the Amsterdam Active Attachment model. The biofilms were then treated with different concentrations of CS, and the antibiofilm effects were evaluated through the quantification of colony-forming units (CFUs), total biomass (TB), metabolic activity (MA), lactic acid production (LAP), and cell viability (by confocal laser scanning microscopy). Chlorhexidine, miconazole, and nystatin were tested as positive controls, while the negative control (NC) was the untreated biofilm. Data were analyzed by 1-way ANOVA and Fischer LSD's post hoc test (α=0.05). RESULTS: MIC values of CS ranged from 500 to 800 µg/mL. For CFUs, 2500 µg/mL CS was the most effective treatment in reducing total anaerobes, mutans streptococci, and Lactobacillus spp., significantly differing from the controls. For C. albicans CFUs, CS and positive controls did not differ from each other but led to significant reductions compared to NC. Regarding TB, MA, LAP, and cell viability, 2500 µg/mL CS promoted the greatest reductions compared to NC. CONCLUSION: CS has similar or superior effects to conventional active principles on important parameters of oral candidiasis microcosm biofilms. CLINICAL RELEVANCE: The antibiofilm effects of CS show that this compound has great potential to improve the clinical condition of denture stomatitis patients, and formulations containing this natural polymer could be useful for controlling oral candidiasis.

A modified Newton classification for denture stomatitis.

The effectiveness of denture stomatitis (DS) treatment should be evaluated by associating clinical and mycological parameters. Although widely used in clinical studies, the Newton classification does not accurately represent the degree of severity of palatal inflammation in terms of extent of the lesions and intensity of the erythema. Therefore, a modified Newton classification has been proposed considering the coverage area of palatal inflammation and the erythema level. This consistent and direct ranking will help standardise randomised clinical trials, as well as the statistical comparison among blind evaluations of the obtained scores within and between studies.

Effect of denture liners surface modification with Equisetum giganteum and Punica granatum on Candida albicans biofilm inhibition.

Aim: This study investigated the effect of denture liners surface modification with Equisetum giganteum (EG) and Punica granatum (PG) on Candida albicans biofilm inhibition supposing its usage as a sustained-release therapeutical delivery system for Candida-associated denture stomatitis. Materials & methods:C. albicans biofilm (SC5314 or ATCC 90028) was formed on soft liners superficially modified by a primer mixed to drugs at minimum inhibitory concentrations (0.100 g for EG and PG or 0.016 g for nystatin per ml of primer). After 24 h, 7 or 14 days, antibiofilm activity was evaluated by colony-forming unit counts. Results: Not all groups were equi-efficient to nystatin after 24 h and 7 days. After 14 days, EG and PG efficacies were not different from nystatin (almost 100% inhibition). Conclusion: The proposed protocol presents a promising option to allopathic drugs for Candida-associated denture stomatitis treatment.

Effect of Denture Hygiene Protocols on Patient Satisfaction, Oral Health-Related Quality of Life, and Salivary Parameters: A Randomized Clinical Trial.

PURPOSE: This randomized controlled trial compared four denture hygiene protocols in terms of patient satisfaction, oral health-related quality of life (OHRQoL), and salivary parameters in complete denture wearers with denture stomatitis. MATERIAL AND METHODS: For this randomized, double-blind, controlled clinical trial, 108 participants were assigned to soak their dentures in one of the following solutions: (1) 0.25% sodium hypochlorite (positive control), (2) 0.15% Triclosan, (3) denture disinfecting tablets, or (4) denture disinfecting tablets plus palatine mucosa brushing solution. The outcomes of patient satisfaction, OHRQoL, and salivary parameters (salivary flow rate and pH) were measured at baseline and after 10 days. The Kruskal-Wallis and Dunn tests (between groups), and Wilcoxon test (between times) were used to compare the results. (α = 0.05). RESULTS: After the hygiene protocols, and when compared with baseline, the overall patient satisfaction, maxillary denture satisfaction, maxillary denture comfort, and maxillary denture retention were ameliorated. A significant improvement was noted in OHRQoL in 3 of 4 domains evaluated (orofacial pain and discomfort, masticatory discomfort and disability, and psychological disability and discomfort). The salivary flow rate (unstimulated and stimulated) and salivary pH were not significantly affected at the times evaluated. CONCLUSIONS: Complete denture wearers may feel more satisfied with their complete dentures when treated for denture stomatitis. The tested treatments lead to similar improvement in terms of patient satisfaction and OHRQoL.

Experimental animal models for denture stomatitis: A methodological review.

Denture stomatitis is the most prevalent form of oral candidiasis and the most frequent oral lesion in removable prosthesis wearers. It is characterized by an inflammatory response of the denture-bearing mucosa, especially the palatal mucosa, and its clinical signs include chronic edema and erythema, and papillary hyperplasia. Despite having a multifactorial etiology, its main etiological agent is the infection by Candida albicans. Given its high treatment failure rates, an in vivo model of denture stomatitis should be established to test alternative treatments. The aim of this study is to review the existing denture stomatitis models and to provide an overview of the main methodological differences between them. Over the last 40 years, different animal models were developed in order to study denture stomatitis etiopathogenesis and to assess novel therapies. Many approaches, including the use of antibiotics and immunosuppressors, have to be further investigated in order to establish which protocol is more appropriate and effective for the development of an animal model of denture stomatitis.

Effect of local hygiene protocols on denture-related stomatitis, biofilm, microbial load, and odor: A randomized controlled trial.

STATEMENT OF PROBLEM: Denture stomatitis affects complete denture wearers and is frequently treated with antifungals drugs, as well as treating the denture with sodium hypochlorite. Whether the limitations of these treatments can be overcome with local hygiene protocols that do not damage the denture materials or adversely affect the patient is unclear. PURPOSE: The purpose of this randomized controlled trial was to evaluate the effect of denture hygiene protocols on complete denture wearers with denture stomatitis. MATERIAL AND METHODS: For this randomized, double-blind controlled clinical trial, 108 participants were assigned to parallel groups: 0.25% sodium hypochlorite (positive control) 0.15% Triclosan, denture cleaning tablets, or denture cleaning tablets plus gingival cleaning tablets. The participants were instructed to brush the dentures and the palate and immerse the denture in the solutions. The outcomes of denture stomatitis remission, biofilm removal, decrease of microbial load (colony-forming units), and odor level of the mouth and denture were measured at baseline and after 10 days. Descriptive analyses were used for sociodemographic characterization of the participants; the Pearson chi-square test was used to compare participant frequency with different degrees of denture stomatitis. The data were not normally distributed (Shapiro-Wilks test) or homogeneous (Levene test). So, the Kruskal-Wallis and Dunn post hoc tests and Wilcoxon test were used to compare the effects of solutions and time on the variables (α=.05). RESULTS: The frequency of the highest to lowest denture stomatitis scores was significantly different for the 0.15% Triclosan and denture cleaning tablets groups. No significant difference was found among the groups in terms of denture stomatitis scores, biofilm, or colony-forming unit count of Candida spp. or C. albicans and S. mutans; a significant reduction was found in these parameters. The 0.25% sodium hypochlorite and 0.15% Triclosan treatments caused a significant reduction in Gram-negative microorganisms; these 2 protocols, and the denture cleaning tablets showed a significant reduction in Staphylococcus spp.; all protocols had similar effects. Only the S. mutans count of the palate decreased after 10 days. The odor level of the mouth and the denture was not significantly different (P=.778). CONCLUSIONS: The evaluated protocols can be recommended for the hygiene of complete dentures, since they were effective for all the variables studied.

Oral Candidiasis and COVID-19 in Users of Removable Dentures: Is Special Oral Care Needed?

Elderly patients with systemic disorders and immunocompromised patients seem to have a higher risk of developing morbidity from COVID-19. Candida albicans (C. albicans) is a potentially dangerous pathogen for these patients, especially for denture wearers with prosthetic stomatitis who require mechanical ventilation. C. albicans infection, the main candidiasis infection associated with denture wear, can complicate COVID-19 and increase the associated morbidity and mortality. Therefore, early diagnosis of C. albicans infection in COVID-19 patients is important to establish more effective antifungal treatment methods and prophylaxis strategies. Hospitalized COVID-19 patients should undergo an oral examination to assess their oral health, and those with poor oral health should receive the appropriate care and monitoring.