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Current Drug Delivery 2023Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans,... (Review)
Review
Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.
Topics: Candidiasis, Oral; Antifungal Agents; Candida; Candida albicans; Photochemotherapy; Phytotherapy; Probiotics
PubMed: 35440307
DOI: 10.2174/1567201819666220418104042 -
Journal of Fungi (Basel, Switzerland) Jan 2021is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals' skin. In 50% of the population, is... (Review)
Review
is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals' skin. In 50% of the population, is part of the normal flora of the microbiota. The various clinical manifestations of 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 '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 '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 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 in the blood is associated with candidemia-invasive infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of . This paper presents the virulence traits of and clinical manifestations of specific candidiasis.
PubMed: 33499276
DOI: 10.3390/jof7020079 -
Journal of Fungi (Basel, Switzerland) Jan 2020Oral candidiasis, commonly referred to as "thrush," is an opportunistic fungal infection that commonly affects the oral mucosa. The main causative agent, , is a highly... (Review)
Review
Oral candidiasis, commonly referred to as "thrush," is an opportunistic fungal infection that commonly affects the oral mucosa. The main causative agent, , is a highly versatile commensal organism that is well adapted to its human host; however, changes in the host microenvironment can promote the transition from one of commensalism to pathogen. This transition is heavily reliant on an impressive repertoire of virulence factors, most notably cell surface adhesins, proteolytic enzymes, morphologic switching, and the development of drug resistance. In the oral cavity, the co-adhesion of with bacteria is crucial for its persistence, and a wide range of synergistic interactions with various oral species were described to enhance colonization in the host. As a frequent colonizer of the oral mucosa, the host immune response in the oral cavity is oriented toward a more tolerogenic state and, therefore, local innate immune defenses play a central role in maintaining in its commensal state. Specifically, in addition to preventing adherence to epithelial cells, saliva is enriched with anti-candidal peptides, considered to be part of the host innate immunity. The T helper 17 (Th17)-type adaptive immune response is mainly involved in mucosal host defenses, controlling initial growth of and inhibiting subsequent tissue invasion. Animal models, most notably the mouse model of oropharyngeal candidiasis and the rat model of denture stomatitis, are instrumental in our understanding of virulence factors and the factors leading to host susceptibility to infections. Given the continuing rise in development of resistance to the limited number of traditional antifungal agents, novel therapeutic strategies are directed toward identifying bioactive compounds that target pathogenic mechanisms to prevent transition from harmless commensal to pathogen.
PubMed: 31963180
DOI: 10.3390/jof6010015 -
The New England Journal of Medicine Jul 2021Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
METHODS
In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority.
RESULTS
A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%).
CONCLUSIONS
In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).
Topics: Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Candidiasis, Oral; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Interleukin-17; Male; Middle Aged; Psoriasis; Severity of Illness Index
PubMed: 33891380
DOI: 10.1056/NEJMoa2102383 -
The Cochrane Database of Systematic... Jan 2022Recurrent vulvovaginal candidiasis (RVVC) affects up to 5% of women. No comprehensive systematic review of treatments for RVVC has been published. (Review)
Review
BACKGROUND
Recurrent vulvovaginal candidiasis (RVVC) affects up to 5% of women. No comprehensive systematic review of treatments for RVVC has been published.
OBJECTIVES
The primary objective was to assess the effectiveness and safety of pharmacological and non-pharmacological treatments for RVVC. The secondary objective was to assess patient preference of treatment options.
SEARCH METHODS
We conducted electronic searches of bibliographic databases, including CENTRAL, MEDLINE, Embase, and CINAHL (search date 6 October 2021). We also handsearched reference lists of identified trials and contacted authors of identified trials, experts in RVVC, and manufacturers of products for vulvovaginal candidiasis.
SELECTION CRITERIA
We considered all published and unpublished randomised controlled trials evaluating RVVC treatments for at least six months, in women with four or more symptomatic episodes of vulvovaginal candidiasis in the past year. We excluded women with immunosuppressive disorders or taking immunosuppressant medication. We included women with diabetes mellitus and pregnant women. Diagnosis of RVVC must have been confirmed by presence of symptoms and a positive culture and/or microscopy. We included all drug and non-drug therapies and partner treatment, assessing the following primary outcomes: • number of clinical recurrences per participant per year (recurrence defined as clinical signs and positive culture/microscopy); • proportion of participants with at least one clinical recurrence during the treatment and follow-up period; and • adverse events.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed titles and abstracts to identify eligible trials. Duplicate data extraction was completed independently by two authors. We assessed risk of bias as described in the Cochrane Handbook for Systematic Reviews of Interventions. We used the fixed-effects model for pooling and expressed the results as risk ratio (RR) with 95% confidence intervals (CI). Where important statistical heterogeneity was present we either did not pool data (I > 70%) or used a random-effects model (I 40-70%). We used the GRADE tool to assess overall certainty of the evidence for the pooled primary outcomes.
MAIN RESULTS
Studies: Twenty-three studies involving 2212 women aged 17 to 67 years met the inclusion criteria. Most studies excluded pregnant women and women with diabetes or immunosuppression. The predominant species found on culture at study entry was Candida albicans. Overall, the included studies were small (<100 participants). Six studies compared antifungal treatment with placebo (607 participants); four studies compared oral versus topical antifungals (543 participants); one study compared different oral antifungals (45 participants); two studies compared different dosing regimens for antifungals (100 participants); one study compared two different dosing regimens of the same topical agent (23 participants); one study compared short versus longer treatment duration (26 participants); two studies assessed the effect of partner treatment (98 participants); one study compared a complementary treatment (Lactobacillus vaginal tablets and probiotic oral tablets) with placebo (34 participants); three studies compared complementary medicine with antifungals (354 participants); two studies compared 'dermasilk' briefs with cotton briefs (130 participants); one study examined Lactobacillus vaccination versus heliotherapy versus ciclopyroxolamine (90 participants); one study compared CAM treatments to an antifungal treatment combined with CAM treatments (68 participants). We did not find any studies comparing different topical antifungals. Nine studies reported industry funding, three were funded by an independent source and eleven did not report their funding source. Risk of bias: Overall, the risk of bias was high or unclear due to insufficient blinding of allocation and participants and poor reporting. Primary outcomes: Meta-analyses comparing drug treatments (oral and topical) with placebo or no treatment showed there may be a clinically relevant reduction in clinical recurrence at 6 months (RR 0.36, 95% CI 0.21 to 0.63; number needed to treat for an additional beneficial outcome (NNTB) = 2; participants = 607; studies = 6; I² = 82%; low-certainty evidence) and 12 months (RR 0.80, 95% CI 0.72 to 0.89; NNTB = 6; participants = 585; studies = 6; I² = 21%; low-certainty evidence). No study reported on the number of clinical recurrences per participant per year. We are very uncertain whether oral drug treatment compared to topical treatment increases the risk of clinical recurrence at 6 months (RR 1.66, 95% CI 0.83 to 3.31; participants = 206; studies = 3; I² = 0%; very low-certainty evidence) and reduces the risk of clinical recurrence at 12 months (RR 0.95, 95% CI 0.71 to 1.27; participants = 206; studies = 3; I² = 10%; very low-certainty evidence). No study reported on the number of clinical recurrences per participant per year. Adverse events were scarce across both treatment and control groups in both comparisons. The reporting of adverse events varied amongst studies, was generally of very low quality and could not be pooled. Overall the adverse event rate was low for both placebo and treatment arms and ranged from less than 5% to no side effects or complications.
AUTHORS' CONCLUSIONS
In women with RVVC, treatment with oral or topical antifungals may reduce symptomatic clinical recurrences when compared to placebo or no treatment. We were unable to find clear differences between different treatment options (e.g. oral versus topical treatment, different doses and durations). These findings are not applicable to pregnant or immunocompromised women and women with diabetes as the studies did not include or report on them. More research is needed to determine the optimal medication, dose and frequency.
Topics: Antifungal Agents; Candidiasis, Oral; Candidiasis, Vulvovaginal; Female; Humans; Immunosuppressive Agents; Pregnancy
PubMed: 35005777
DOI: 10.1002/14651858.CD009151.pub2 -
The New England Journal of Medicine Jul 2021Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necrosis factor inhibitor adalimumab in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
METHODS
We randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. The primary end points were a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 90 response; PASI scores range from 0 to 72, with higher scores indicating worse disease) and an Investigator's Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (scores range from 0 [clear skin] to 4 [severe disease]), at week 16. The analysis of the primary end points tested noninferiority at a margin of -10 percentage points and then tested for superiority.
RESULTS
A total of 614 patients were screened, and 478 were enrolled; 158 patients were assigned to receive bimekizumab every 4 weeks, 161 to receive bimekizumab every 4 weeks and then every 8 weeks, and 159 to receive adalimumab. The mean age of the patients was 44.9 years; the mean PASI score at baseline was 19.8. At week 16, a total of 275 of 319 patients (86.2%) who received bimekizumab (both dose groups combined) and 75 of 159 (47.2%) who received adalimumab had a PASI 90 response (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) who received bimekizumab and 91 of 159 (57.2%) who received adalimumab had an IGA score of 0 or 1 (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority). The most common adverse events with bimekizumab were upper respiratory tract infections, oral candidiasis (predominantly mild or moderate as recorded by the investigator), hypertension, and diarrhea.
CONCLUSIONS
In this 56-week trial, bimekizumab was noninferior and superior to adalimumab through 16 weeks in reducing symptoms and signs of plaque psoriasis but was associated with a higher frequency of oral candidiasis and diarrhea. Longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. (Funded by UCB Pharma; BE SURE ClinicalTrials.gov number, NCT03412747.).
Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Candidiasis, Oral; Diarrhea; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Interleukin-17; Male; Middle Aged; Psoriasis; Severity of Illness Index
PubMed: 33891379
DOI: 10.1056/NEJMoa2102388 -
Virulence Dec 2020In the last decades, has served as the leading causal agent of life-threatening invasive infections with mortality rates approaching 40% despite treatment. exists in... (Review)
Review
In the last decades, has served as the leading causal agent of life-threatening invasive infections with mortality rates approaching 40% despite treatment. exists in three biological phases: yeast, pseudohyphae, and hyphae. Hyphae, which represent an important phase in the disease process, can cause tissue damage by invading mucosal epithelial cells then leading to blood infection. In this review, we summarized recent results from different fields of fungal cell biology that are instrumental in understanding hyphal growth. This includes research on the differences among phases; the regulatory mechanism of hyphal growth, extension, and maintaining cutting-edge polarity; cross regulations of hyphal development and the virulence factors that cause serious infection. With a better understanding of the mechanism on mycelium formation, this review provides a theoretical basis for the identification of targets in candidiasis treatment. It also gives some reference to the study of antifungal drugs.
Topics: Candida albicans; Candidiasis; Fungal Proteins; Gene Expression Regulation, Fungal; Humans; Hyphae; Virulence
PubMed: 32274962
DOI: 10.1080/21505594.2020.1748930 -
Dermatologic Clinics Oct 2020Chronic oral mucosal lesions can be associated with several mucocutaneous diseases. This article reviews the autoimmune and immune-mediated, reactive, genetic, and... (Review)
Review
Chronic oral mucosal lesions can be associated with several mucocutaneous diseases. This article reviews the autoimmune and immune-mediated, reactive, genetic, and infectious diseases that may present with chronic oral and/or cutaneous manifestations and provides a rational approach to diagnosis and management.
Topics: Autoimmune Diseases; Behcet Syndrome; Candidiasis, Oral; Chronic Disease; Fibroma; Graft vs Host Disease; Humans; Keratosis; Leukokeratosis, Hereditary Mucosal; Lichen Planus, Oral; Mouth Diseases; Papillomavirus Infections; Skin Diseases, Vesiculobullous; Stomatitis; Tobacco Products
PubMed: 32892854
DOI: 10.1016/j.det.2020.05.006