A systematic review of the management of oral candidiasis associated with HIV/AIDS.

The purpose of this review was to investigate the management of oral candidiasis in HIV/AIDS patients and to evaluate the different guidelines available for its management. A number of topical and systemic antifungal medications are used to treat oral candidiasis in HIV-positive patients. Milder episodes of oral candidiasis respond to topical therapy with nystatin, clotrimazole troches or oral ketoconazole. Fluconazole has been extensively evaluated as a treatment for candidiasis. With HIV-infection, a cure rate of 82% has been achieved with a daily oral dose of 50 mg. Fluconazole was found to be a better choice of treatment for relapsing oropharyngeal candidiasis, resulting in either better cure rates or better prevention of relapse. Intravenous amphotericin B has been found to be effective in azole-refractory candidiasis and is well tolerated. Topical therapies are effective for uncomplicated oropharyngeal candidiasis; however, patients relapsed more quickly than those treated with oral systemic antifungal therapy. Nystatin appeared less effective than clotrimazole and the azoles in the treatment of oropharyngeal candidiasis. Clotrimazole was found to be just as effective for resolution of clinical symptoms as the azoles, except when patient compliance was poor. Fluconazole-treated patients were more likely to remain disease-free during the fluconazole follow-up period than those treated with other antifungal agents.     

Comparative trial of oral clotrimazole and nystatin for oropharyngeal candidiasis prophylaxis in orthotopic liver transplant patients.

A prospective randomized study was conducted to assess the effectiveness of clotrimazole troches and nystatin suspension to prevent oral candidiasis in immunosuppressed orthotopic liver transplant patients. Thirty-four patients received either clotrimazole troches, 10 mg, five times daily, or nystatin suspension, 500,000 units, four times daily. Prophylaxis was initiated after extubation after transplantation and continued throughout the hospitalization. One of 17 patients in each treatment group developed clinical and microscopic evidence of an oropharyngeal Candida infection. This gave an intragroup and an overall infection rate of 5.9%. It appears that either nystatin or clotrimazole may be used for candidiasis prophylaxis in orthotopic liver transplant patients.     

Comparison of efficacy of fluconazole mouthrinse and clotrimazole mouthpaint in the treatment of oral candidiasis

Candidiasis is by far the most common oral fungal infection in humans and has a variety of clinical features. It is considered to be an opportunistic infection, affecting individuals who are debilitated by another disease. Fluconazole, one of the newer azoles available for systemic use and clotrimazole as a topical ointment are both shown to be effective in the treatment of oral candidiasis and are considered to be well tolerated and useful medications. No study has evaluated the comparison of clinical and mycological response of oral candidiasis to fluconazole mouthrinse and clotrimazole mouthpaint. The aim of this study was to evaluate the efficacy of fluconazole mouthrinse and compare it with clotrimazole mouthpaint in the treatment of oral candidiasis.     

The epidemiology of non-albicans Candida in oropharyngeal candidiasis in HIV patients

Oropharyngeal candidiasis (OPC) is the most common fungal infection In patients with HIV infection. Fluconazole has been proven to be very effective In treating this Infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole than C. albicans and are being Isolated with Increased frequency in HIV patients. The purpose of this study was to determine if the presence of non-albicans Candida with OPC in HIV patients had an Impact on clinical presentation. This study shows that latestage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially non-albicans species. OPC episodes with non-albicans Isolates were more likely to require higher doses of fluconazole to achieve clinical cure. Also, the presence of non-albicans Candida was more frequently associated with severe symptoms.     

Efficacy of antifungal drugs in the treatment of oral candidiasis: A Bayesian network meta-analysis

Statement of problemThe comparative efficacy of antifungal drugs on oral candidiasis remains unclear.PurposeThe purpose of this Bayesian network meta-analysis was to investigate the efficacy of antifungal drugs on oral candidiasis.Material and methodsDatabases, including PubMed, The Cochrane Library, and Web of Science, were accessed from the dates of their establishment to October, 2018, to collect randomized controlled trials (RCTs) of different antifungal drugs for oral candidiasis. A network meta-analysis was then conducted by using R and Stata 12.0 software programs.ResultsA total of 31 RCTs involving 4042 participants were included. The meta-analysis showed that, in the treatment of oral candidiasis in reducing the mycological cure rate, itraconazole capsules, itraconazole oral solution, miconazole buccal tablets, miconazole oral gel, clotrimazole, fluconazole, ketoconazole, nystatin, and amphotericin B were better than a placebo. Miconazole oral gel, fluconazole, and ketoconazole were better than nystatin. The network meta-analysis also showed that the effects of antifungal drugs in reducing the mycological cure rate in oral candidiasis were better than those of a placebo: itraconazole capsule (OR=1.20, 95% CrI: 1.07-1.34), itraconazole oral solution (OR=1.50, 95% CrI: 1.14-1.86), miconazole buccal tablet (OR=2.80, 95% CrI: 1.20-4.50), miconazole oral gel (OR=2.90, 95% CrI: 1.70-4.30), clotrimazole (OR=3.80, 95% CrI: 1.65-5.95), fluconazole (OR=2.40, 95% CrI: 1.10-3.80), ketoconazole (OR=3.40, 95% CrI: 1.76-7.04), nystatin (OR=2.50, 95% CrI: 1.43-3.57), and amphotericin B (OR=2.60, 95% CrI: 1.91-3.29). The SUCRA values for each antifungal drug were as follows: placebo (6.80%), itraconazole capsule (51.2%), itraconazole oral solution (75.2%), miconazole buccal tablet (34.4%), miconazole oral gel (76.9%), clotrimazole (64.8%), fluconazole (79.3%), ketoconazole (50.7%), nystatin (15.7%), and amphotericin B (44.4%).ConclusionsAntifungal drugs have efficacy in the treatment of oral candidiasis. The effect of fluconazole in reducing the risk of the mycological cure rate in oral candidiasis was better than that of other drugs.     

A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis

The use of dental varnish for therapeutic purposes has been reported for fluoride or antibacterial drugs. Our objectives were to develop a sustained-release varnish containing an antifungal drug (clotrimazole) for topical application and to evaluate the release rate of the drug in human saliva in comparison with an available commercial troche and their acceptance by healthy volunteers. Following in vitro optimization of the release rate from the varnish, we have embarked on a crossover comparative study assessing the oral sensations and pharmacokinetics of a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed for clotrimazole concentration by high performance liquid chromatography analysis. The volunteers’ evaluation of the varnish and troche (taste, other sensory changes, convenience, and oral suitability) were recorded. At all time points, salivary clotrimazole concentrations were higher, and the terminal half-life was significantly prolonged in the varnish group in comparison to the control group. This can be attributed to continuous release of clotrimazole from the varnish formulation. The duration of the drug over the minimal inhibitory concentration, following application of the varnish, was more than threefold longer than following administration of the troche. The developed sustained-release varnish can be applied in patients at a lower frequency than troches, thus, achieving higher patient compliance and efficacy. This novel varnish application can serve as the basis for a new treatment approach to oral candidiasis, a very common chronic opportunistic infection with improved clinical outcome.     

Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer

Oropharyngeal candidiasis (OPC) is relatively common in patients receiving radiation for head and neck cancer occurring in approximately 25% of patients. Candida albicans has been described as the primary infecting organism. Recently, other organisms, particularly Candida glabrata, have emerged as causative agents of OPC among immunocompromised patients. This study describes the characteristics of 6 patients with head and neck cancer treated with radiotherapy at our institution, who were found to have Candida glabrata-associated OPC and their responses to oral fluconazole. All 6 patients were successfully treated with oral fluconazole. However, most did not respond to the usual dose of 100 mg/day necessitating doses ranging from 200 to 800 mg/day to achieve clinical cure. All 3 patients receiving radiation only were successfully treated with up to 200 mg/day; 2 of 3 patients receiving concomitant chemoradiation required doses ranging from 400 to 800 mg/day. As with systemic infection, previous fluconazole use appears to be a risk factor for this infection, but not with all patients.     

(B1) Candida and mycotic infections

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.     

Fluconazole mouthrinses for oral candidiasis in postirradiation,transplant, and other patients

OBJECTIVE: Oral candidiasis is associated with multiple local and systemic factors. Morbidity and deaths, in high-risk patients, may be prevented by recognition and adequate management. Fluconazole is a systemic antifungal medication that demonstrated clinical advantages in rinsing before swallowing. The purpose of the present study was to evaluate the clinical efficacy of fluconazole aqueous mouthrinses to treat oral candidiasis. METHODS: Ten women and 9 men diagnosed with oral candidiasis used fluconazole (2 mg/mL) aqueous solution 3 times per day as a rinse and-spit topical treatment. The outcome was assessed after 1 week of treatment. RESULTS: Complete symptomatic and clinical relief was noted in 94% of the patients, and a mycologic cure was documented in all but 1 patient. No side effects were reported. Oral rinses with fluconazole suspension may be useful to manage patients with dry mouth or those who have difficulties in swallowing caused by oral candidiasis. CONCLUSIONS: Further double-blind studies are needed to establish the optimal treatment regimen and the usefulness of fluconazole mouthrinses in patients with different risk factors for infection.     

Refractory oral candidiasis. Report of a case.

A 55-year-old male patient with no significant medical history or systemic physical findings was found, on routine dental examination, to have an oral Candida albicans infection. The condition failed to clear completely after 21 days of nystatin therapy. A 5-day course of clotrimazole was then initiated. Complete clearing of all signs of candida infection occurred in 48 hours, but the infection recurred by the twentieth day of follow-up. A 14-day regimen was then prescribed. Again, the condition cleared in 48 hours, and at the 6-month follow-up all signs of candida involvement, including cultures and smears, remained negative. As no reports of the use of clotrimazole vaginal tablets in oral candidiasis clinically refractory to nystatin therapy were found in the literature of the last 11 years, it was thought that this case was of significant interest.     

Prophylaxis of candidiasis in patients with leukemia and bone marrow transplants

ObjectivesThe increased risk for systemic fungal infection and the potential fatal consequences of disseminated candidiasis in bone marrow transplant patients has prompted study of prophylaxis and early treatment of candida colonization and infection.Study designPatients with leukemia who received fluconazole prophylaxis were compared with a concurrent group ofpatients not given prophylaxis for fungal organisms.ResultsA trend to reduction of oropharyngeal colonization by Candida albicans was seen (p=0.07) although no significant differences in systemic candidiasis were seen. In patients with documented systemic candidiasis, oral colonization was present and systemic infection was identified after the development of ulcerative oral mucositis.ConclusionsOur results support the potential of fluconazole to reduce oropharyngeal colonization caused by Candida albicans, however, we did not show prophylaxis of oral candidiasis or systemic candidiasis. These findings and reports of fluconazole-resistant candidal species and a rising number of cases of infection as a result of Candida krusei indicate the need for further studies of prophylaxis of candidal infection in patients who are anticipated to develop profound neutropenia.     

Longitudinal monitoring of subgingival colonization by Actinobacillus actinomycetemcomitans, and crevicular alkaline phosphatase and aspartate aminotransferase activities around orthodontically treated teeth

OBJECTIVES: During orthodontic treatment, changes in subgingival plaque colonization and tissue inflammation and remodelling have been described. This study uses a longitudinal design to examine subgingival colonization of Actinobacillus actinomycetemcomitans (Aa) and alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities in gingival crevicular fluid (GCF) in order to assess whether these parameters have potential as biomarkers of tissue responses to orthodontic tooth movement in humans. MATERIALS & METHODS: Twenty-one patients (ages: 11.2-22.5; mean 17.1 +/- 3.3 years) participated in the study. An upper canine from each patient undergoing treatment for distal movement served as the test tooth (DC), and its contralateral (CC) and antagonist (AC) canines were used as controls. The CC was included in the orthodontic appliance, but was not subjected to the orthodontic force; the AC was free from any orthodontic appliance. The subgingival plaque and GCF around the experimental teeth was harvested from both mesial and distal tooth sites immediately before appliance activation and on day 28. Clinical gingival condition was evaluated at the baseline and at the end of the experimental period. Aa colonization was determined by culture methods, while ALP and AST activities were evaluated spectrophotometrically. RESULTS: Throughout the study, the clinical conditions worsened in both the DCs and the CCs as compared with the baseline, whereas no significant differences were found between the DCs and the CCs, or between mesial and distal sites of each of these teeth on day 28. In the ACs, clinical parameters remained at baseline levels throughout the study. Similar results were found for Aa colonization, which increased significantly on day 28 in the DC and CC groups. On day 28, ALP and AST activities were significantly elevated in all sites from the DC and CC groups as compared with the ACs, where, conversely, enzymatic activities remained at the baseline levels. However, ALP activity in the DC group was significantly greater than in the CCs at mesial (tension) sites on day 28, while AST activity in the DCs was significantly elevated as compared with the CC group at the distal (compression) sites. Greater ALP activity in the DC group was observed at the tension sites compared with the compression sites on day 28. CONCLUSIONS: Our results suggest that Aa subgingival colonization, and ALP and AST activities in GCF reflect the tissue responses that occur in the periodontium during orthodontic treatment.     

Treatment of angular cheilitis. The significance of microbial analysis, antimicrobial treatment, and interfering factors

This prospective study evaluated the significance of microbial analysis and antimicrobial treatment for the cure of angular cheilitis. Furthermore, various etiologic factors were investigated for their relative effect on the healing process. The study included 1) an open trial with 50 patients infected by Candida albicans and/or Staphylococcus aureus, and 2) an intraindividual comparison of eight patients with bilateral lesions infected by Candida albicans as the only detected pathogen. After a base-line examination the patients received ointments containing nystatin and/or fusidic acid, on the basis of the outcome of an initial microbial analysis. The patients were evaluated clinically, photographed, and examined for microorganisms at different time intervals. Ninety-six per cent of the patients who participated in the open trial had no sign of infection after 42 days of treatment. Lesions in the double-blind study, treated with nystatin, were healed after 28 days, whereas lesions that received placebo persisted throughout the treatment period. Increasing age, dry skin, and extended skinfolds at the corner of the mouth were factors closely related to the length of the healing process.     

Comparison of different treatment methods for localized and generalized simple denture stomatitis

SUMMARY The purpose of this study was to compare the treatment effects of fluconazole, fluconazole plus chlorhexidine and the fitting of new dentures upon the treatment of denture stomatitis and 15 subjects with clinical evidence of localized simple denture stomatitis were investigated clinically and mycologically. Patients with clinical evidence of generalized simple denture stomatitis were divided into three treatment groups. The first group was given 50 mg of fluconazole tablets daily for 2 weeks. The second group were instructed to apply chlorhexidine solution to the inner surface of the denture twice a day in addition to fluconazole treatment for 2 weeks. New dentures were constructed for the third group. Patients with clinical evidence of localized simple denture stomatitis were fitted new dentures without antifungal therapy. Palatal swabs were taken from each subject before, immediately after, and 2 weeks after the end of treatment, and the samples were examined mycologically in order to identify yeast colonies. It was found that for generalized simple denture stomatitis, treatment with fluconazole plus chlorhexidine resulted in better improvement of palatal inflammation than that by either fluconazole or the fitting of new dentures without medication. Whereas fitting new dentures did not reduce inflammation in patients with generalized simple denture stomatitis, the beneficial effects of prosthetic treatment were seen in patients with localized simple denture stomatitis.     

Characterization of the mycoflora from oral mucosal surfaces of some HIV-infected patients

Oral mucosal surfaces from 54 patients seropositive for human immunodeficiency virus (HIV) were assayed for the presence of cultivable yeasts. Oral colonization with Candida albicans, represented by 6 biotypes, was evident in 35 persons. The closely related variant, Candida stellatoidea, was found in 3 patients. Single isolates of Candida parapsilosis, Candida glabrata, Candida tropicalis, and Candida paratropicalis were also identified. One patient harbored a population of Saccharomyces cerevisiae. The susceptibilities of these 43 isolates to clotrimazole and nystatin were compared by the disk diffusion technique.     

A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients

OBJECTIVE: A systematic review of randomized clinical trials published between 1966 and April 2000 was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis in human immunodeficiency virus-positive patients. STUDY DESIGN: An automated database search identified 366 articles. Six met inclusion and exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of oral candidiasis. RESULTS: The evidence for the prophylactic efficacy of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole. CONCLUSION: Suggestions for strengthening the evidence base include the following: use of larger, more well-defined groups; control for immunologic status, viral load, history of oral candidiasis, past exposure to antifungals, baseline oral Candida carriage, drug interactions, and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing.     

Innovations for prevention and care of oral candidiasis in HIV‐infected individuals: Are they available?—A workshop report

Oral candidiasis (OC) is the most prevalent HIV‐related oral lesion in patients on combined anti‐retroviral therapy (cART) or without cART. Management is challenged in some patients by development of resistance to azole drugs, such as fluconazole. Recent scientific knowledge about OC pathogenesis, the role of OC in the immune reconstitution inflammatory syndrome (IRIS), the relationship of OC with the microbiome, and novelties in OC treatment was discussed in an international workshop format. Literature searches were conducted to address five questions: (a) Considering the pathogenesis of Candida spp. infection, are there any potential therapeutic targets that could be considered, mainly in HIV‐infected individuals resistant to fluconazole? (b) Is oral candidiasis part of IRIS in HIV patients who receive cART? (c) Can management of the oral microbiome reduce occurrence of OC in patients with HIV infection? (d) What are the recent advances (since 2015) regarding plant‐based and alternative medicines in management of OC? and (e) Is there a role for photodynamic therapy in management of OC in HIV‐infected patients? A number of the key areas where further research is necessary were identified to allow a deeper insight into this oral condition that could help to understand its nature and recommend alternatives for care.     

��������ȱ�ݲ�����Ⱦ���߿�ǻ�����ֲ״������

目的探索人类免疫缺陷病毒（HIV）感染或艾滋病（AIDS）患者口腔真菌定植状况及菌种分布,为HIV感染或AIDS患者真菌感染防治提供理论依据。方法选择2013年6—12月在新疆医科大学第一附属医院感染科就诊的HIV感染或AIDS患者30例,由口腔科采用咽拭子法收集口腔分泌物,通过真菌培养实验分析口腔真菌定植状况。结果 30例HIV感染或AIDS患者中,阳性带菌者19例,阳性率为63.3%。阳性带菌者年龄2~52岁;其中男13例（68.4%）、女6例（31.6%）;维吾尔族15例（78.9%）,汉族4例（21.1%）。阳性带菌者中携带白色念珠菌15例（78.9%）。结论白色念珠菌为HIV感染或AIDS患者口腔真菌定植的主要菌种。阳性带菌者年龄分布广泛。     

Effect of nystatin in the treatment of denture stomatitis

The effect of nystatin treatment on denture stomatitis subclassified as generalized simple inflammation and inflammatory papillary hyperplasia has been studied. Twenty-four patients were carefully instructed to apply a thin layer of nystatin dusting powder on the fitting surface of the maxillary denture three times a day for 14 d. Different parameters were studied on three occasions; at the beginning of experiment and after 14 and 28 d. An untreated group of 24 patients with the same types of denture stomatitis served as control. The effect of treatment was. evaluated by changes in the clinical erythema, the yeast colonization obtained by mycologic sampling on the palatal mucosa and on the denture base, and changes in the histologic picture of the mucosa obtained by biopsy. Subepithelial inflammation, leukocyte penetration, edema and thickness of the epithelium were histologic parameters. After 14 d of treatment the experimental group compared with the control group showed a statistically significant decrease in palatal erythema and in the amount of yeast colonies. No significant changes were found microscopically. Twenty-eight days after start, i.e. 14 d after withdrawal of the nystatin, there still was a statistically significant improvement of the palatal erythema in the experimental group compared with the controls. However, no patient was totally cured. There were no significant changes in the number of yeast colonies and the histologic parameters.     

Genotypic relatedness of yeasts in thrush and denture stomatitis

BACKGROUND/AIM: Candida is an opportunistic pathogen. Understanding its genetic characters might increase our understanding of the pathogenesis of candidosis. We examined the genetic relationships of yeasts from the most common forms of oral candidosis: thrush and denture stomatitis. METHODS: Yeasts were sampled from palate, buccal mucosa, gingival sulci/periodontal pockets and/or denture fitting surface of 19 thrush patients and 22 denture stomatitis patients. Random amplified polymorphic DNA and the Dendron computer-assisted program were used to determine the genotypic relatedness of the yeasts. RESULTS: A dendrogram generated from 105 thrush isolates had similarity coefficients (S(AB)) ranging from 0.58 to 1 with four clusters derived at S(AB) 68%. Another dendrogram was generated from 91 isolates from denture stomatitis, with S(AB) ranging from 0.59 to 1. Three clusters were established at S(AB) 71%. In a composite dendrogram incorporating the thrush and denture stomatitis data and orally healthy data compiled from a previous study, five genotypic clusters were generated at S(AB) 68%. Cluster II, the most dominant, comprised isolates from thrush, denture stomatitis and healthy conditions, while clusters III and IV contained yeasts mainly from thrush. CONCLUSIONS: Palatal yeast carriage was significantly increased in thrush and denture stomatitis, also after radiation, chemotherapy and denture wearing. The buccal mucosa was favorable for yeast colonization regardless of oral condition. Yeasts in thrush were more diverse than in conditions of oral health. The common clone (II) of infecting yeasts and commensals suggested that commensals could induce thrush and denture stomatitis, whereas the unique clones in thrush (III, IV) might have been established through strain replacement or maintenance with minor genetic variation.