Oropharyngeal Candidosis Research Articles

Oral Candidosis: Pathophysiology and Best Practice for Diagnosis, Classification, and Successful Management.

Oral candidosis is the most common fungal infection that frequently occurs in patients debilitated by other diseases or conditions. No candidosis happens without a cause; hence oral candidosis has been branded as a disease of the diseased. Prior research has identified oral candidosis as a mark of systemic diseases, such as hematinic deficiency, diabetes mellitus, leukopenia, HIV/AIDS, malignancies, and carbohydrate-rich diet, drugs, or immunosuppressive conditions. An array of interaction between Candida and the host is dynamic and complex. Candida exhibits multifaceted strategies for growth, proliferation, evasion of host defenses, and survival within the host to induce fungal infection. Oral candidosis presents a variety of clinical forms, including pseudomembranous candidosis, erythematous candidosis, angular cheilitis, median rhomboid glossitis, cheilocandidosis, juxtavermillion candidosis, mucocutaneous candidosis, hyperplastic candidosis, oropharyngeal candidosis, and rare suppurative candidosis. The prognosis is usually favorable, but treatment failure or recurrence is common due to either incorrect diagnosis, missing other pathology, inability to address underlying risk factors, or inaccurate prescription of antifungal agents. In immunocompromised patients, oropharyngeal candidosis can spread to the bloodstream or upper gastrointestinal tract, leading to potentially lethal systemic candidosis. This review therefore describes oral candidosis with regard to its pathophysiology and best practice for diagnosis, practical classification, and successful management.

Oropharyngeal Candidosis in HIV-Infected Patients-An Update.

Oropharyngeal candidosis (OPC) is an opportunistic fungal infection that is commonly found in HIV-infected patients, even in the twenty-first century. Candida albicans is the main pathogen, but other Candida species have been isolated. OPC usually presents months or years before other severe opportunistic infections and may indicate the presence or progression of HIV disease. The concept of OPC as a biofilm infection has changed our understanding of its pathobiology. Various anti-fungal agents (both topical and systemic) are available to treat OPC. However, anti-fungal resistance as a result of the long-term use of anti-fungal agents and recurrent oropharyngeal infection in AIDS patients require alternative anti-fungal therapies. In addition, both identifying the causative Candida species and conducting anti-fungal vulnerability testing can improve a clinician's ability to prescribe effective anti-fungal agents. The present review focuses on the current findings and therapeutic challenges for HIV-infected patients with OPC.

Клініко-ендоскопічні аспекти кандидозу слизової оболонки верхнього відділу шлунково-кишкового тракту у пацієнтів з гастроентерологічною патологією

Стаття присвячена розв’язанню актуальних питань взаємозв’язку клінічних та ендоскопічних аспектів кандидозу слизової оболонки (СО) верхнього відділу шлунково-кишкового тракту. Результати досліджень, проведених у 122 пацієнтів, дозволили виявити превалювання диспептичного синдрому в пацієнтів із даною патологією, при цьому в пацієнтів з ураженням стравоходу інтенсивність синдрому абдомінального болю в 1,5 раза перевищує таку в групі лише з орофарингеальним кандидозом (р < 0,001). Більш глибоке ураження СО асоціюється зі збільшенням частоти виявлення макроскопічних ознак запалення у стравоході (р < 0,05), нальоту на язику (r = 0,220; р = 0,02), утруднення проходження їжі стравоходом (r = 0,235; р = 0,02), болю за грудниною (r = 0,249; р = 0,01) при відсутності впливу таких факторів, як шлунково-стравохідний і дуоденогастральний рефлюкси. Виявлений прямий взаємозв’язок макроскопічних ознак запалення і рубцевої деформації в цибулині дванадцятипалої кишки зі ступенем кандидозу (r = 0,250; р = 0,01). У цілому аналіз отриманих даних показав необхідність подальшого осмислення ролі опортуністичної інфекції у формуванні патологічних процесів і розвитку захворювань.

Oropharyngeal candidosis relative frequency in radiotherapy patient for head and neck cancer

Background:Radiation given during treatment of oral and pharyngeal malignancy frequently causes alteration of the oral environment predisposing to the colonization of the oral mucosa by yeast species most frequently Candida.Objective:Thus, this study was undertaken in 107 patients to find out association between radiation therapy and frequency of oropharyngeal candidosis, to quantitate colony forming units (CFUs) to identify Candida at species level and to check the incidence of serotype A and B in C. albicans.Materials and Methods:The study was done on patients suffering from oropharyngeal cancer who were advised radiotherapy. The oral rinse collection method was used to collect the sample. Sabourauds Dextrose Agar (SDA) was used as primary culture media and subsequently speciation was done using standard techniques. The strains of C. albicans were serotyped employing the method described by Hansclever and Mitchell (1961, J Bacteriol 1961;82:570-3).Results:26.16% patients were mycologically positive for candida before radiotherapy with CFUs 100. 14 ± 59.11 that increased to 60.74% patients during radiotherapy with an increase in CFUs to 490.15 ± 207.97. Clinically, grading of mucositis was done and also individual signs and symptoms were noted in each patient. The occurrence of erythmatous lesions, ulceration, and xerostomia were found to be statistically significant (P<0.05). C. albicans was the most frequently encountered species with higher prevalence of serotype A suggesting higher virulent species.Conclusion:It is proposed that in such patients taking radiotherapy prophylactic antifungal treatment should be given specially in patients showing development of oral mucosal lesions such as erythmatous lesions, ulcerations, and complaining about dryness of mouth, that is, xerostomia irrespective of presence or absence of clinical oral candidosis.

Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients

Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and α-terpineol, with an MIC50 of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and α-terpineol displayed rapid kill kinetics. For all three compounds, 1 × MIC50 effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2 h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1 × MIC50, whereas at 0.5 × MIC50 T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration.

Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial

Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda. In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per μL, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per μL (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN 76481529. Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=0·0001); adjusted HR (aHR) 18·7 (95% CI 2·5-140·7). One case of cryptococcal disease could be prevented by treating 44·6 patients with baseline CD4 counts lower than 200 cells per μL. Fluconazole was effective against cryptococcal disease both before (aHR=11·0 [1·4-85·3]) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All-cause mortality (n=189) did not differ between the two groups (p=0·46). Fluconazole reduced the time to first episode of oesophageal, and oropharyngeal and vaginal candidosis, as well as the incidence of all candidosis (p<0·0001), but had no effect on hospital admission or death. The frequency of elevated transaminases (>5×ULN) was similar between groups (aHR=0·94 [0·65-1·35]). Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease, both before and during early antiretroviral treatment. Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg. In patients with negative CrAg on screening, fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy, particularly in those with CD4 counts of less than 100 cells per μL. Medical Research Council, UK, and Rockefeller Foundation.

Difference in virulence between fluconazole‐susceptible and fluconazole‐resistant Candida albicans in a mouse model

Two Candida albicans isolates were collected from a HIV-positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU-S), minimal inhibitory concentration (MIC) = 0.25 mg l(-1) ] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU-R, MIC = 64 mg l(-1)). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU-S isolate survived the experiment when FLU was given. However, when FLU was absent, the mortality of the FLU-S isolate was higher than that of the FLU-R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU-S isolate and a more intense biofilm-building activity compared with the FLU-R isolate. The FLU-R isolate highly up-regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. The results showed that FLU-S and FLU-R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.

CANDIDOSIS OF MUCOUS MEMBRANES OF ORAL CAVITY OF THE HIV-INFECTED

The article presents the structure of fungal agents of mucous membranes of oral cavity of the HIV-infected. The majority of infection is caused by Candida albicans (82 %). The fact of revealing of or absence of growth of fungi did not depend on the indicators of the immune status. The quantity of fungi of the HIV-infected with various immune status was definitely different. Fluconazole-refractory oropharyngeal candidosis revealed in 38,4 % of HIV-infected patients. Amfotericin B is effective among patients with oropharyngeal candidosis.

Longitudinal Genotyping of Candida dubliniensis Isolates Reveals Strain Maintenance, Microevolution, and the Emergence of Itraconazole Resistance

We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.

Data mining validation of fluconazole breakpoints established by the European Committee on Antimicrobial Susceptibility Testing.

European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints classify Candida strains with a fluconazole MIC < or = 2 mg/liter as susceptible, those with a fluconazole MIC of 4 mg/liter as representing intermediate susceptibility, and those with a fluconazole MIC > 4 mg/liter as resistant. Machine learning models are supported by complex statistical analyses assessing whether the results have statistical relevance. The aim of this work was to use supervised classification algorithms to analyze the clinical data used to produce EUCAST fluconazole breakpoints. Five supervised classifiers (J48, Correlation and Regression Trees [CART], OneR, Naïve Bayes, and Simple Logistic) were used to analyze two cohorts of patients with oropharyngeal candidosis and candidemia. The target variable was the outcome of the infections, and the predictor variables consisted of values for the MIC or the proportion between the dose administered and the MIC of the isolate (dose/MIC). Statistical power was assessed by determining values for sensitivity and specificity, the false-positive rate, the area under the receiver operating characteristic (ROC) curve, and the Matthews correlation coefficient (MCC). CART obtained the best statistical power for a MIC > 4 mg/liter for detecting failures (sensitivity, 87%; false-positive rate, 8%; area under the ROC curve, 0.89; MCC index, 0.80). For dose/MIC determinations, the target was >75, with a sensitivity of 91%, a false-positive rate of 10%, an area under the ROC curve of 0.90, and an MCC index of 0.80. Other classifiers gave similar breakpoints with lower statistical power. EUCAST fluconazole breakpoints have been validated by means of machine learning methods. These computer tools must be incorporated in the process for developing breakpoints to avoid researcher bias, thus enhancing the statistical power of the model.

Development and characterization of lectin-functionalized vesicular constructs bearing amphotericin B for bio-film targeting

The long-term goal of this work will be to develop a topical formulation for oropharyngeal candidosis. Liposomes were prepared by the vesicle extrusion technique from mixtures of dipalmitoylphosphatidylcholine, cholesterol, and stearylamine incorporating a reactive phospholipid, the m-maleimidobenzoyl-N-hydroxysuccinimide ester derivative of dipalmitoylphosphatidylethanolamine, which was conjugated with the N-succinimidyl-S-acetylthioacetate derivatives of succinyl concanavalin A. Morphology of liposomes was studied by transmission electron microscopy and bio-film architecture using fluorescence microscopy. Lectinized vesicles were put into contact with bovine submaxillary mucin, to determine the in vitro activity and specificity. Targeting study was performed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The liposomes were found to have a diameter in the range of 360–450 and 390–510 nm for uncoated and coated formulations, respectively. The MTT assay showed a strong association of lectin-bearing liposomes with candidal bio-film. The results suggest that surface-modified liposomes can effectively target candidal bio-film in vitro.

Multifocal squamous cell carcinomas in an HIV-infected patient with a long-term voriconazole therapy

Multifocal squamous cell carcinomas in an HIV-infected patient with a long-term voriconazole therapy

HIV-1 anti-retroviral drug effect on the C. albicans hyphal growth rate by a Bio-Cell Tracer system

Declining incidence of oropharyngeal candidosis and opportunistic infections over recent years can be attributed to the use of highly active anti-retroviral therapy (HAART). Infection with C. albicans generally involves adherence and colonization of superficial tissues. During this process, budding yeasts are able to transform to hyphae and penetrate into the deep tissue. Using the biocell tracer system, C. albicans hyphal growth was dynamically observed at the cellular level. Ritonavir was effective in the inhibition of hyphal growth with growth rate of 0.8 mm/min. This study showed the in vitro effect of HIV anti-retroviral drug on the growth rate of the C. albicans hyphae.

The first description of an oesophageal candidosis by Bernhard von Langenbeck in 1839

In November 1839 the young university lecturer Bernhard (von) Langenbeck (1810-1887) published the first description of a fungus as aetiological agent of an oro-pharyngeal and oesophageal candidosis. We present his in English translated paper entitled 'Finding of fungi on the mucous membrane of the gullet of a typhoid fever corpse' (Germ.) in 'Neue Notizen aus dem Gebiete der Natur- und Heilkunde' (Froriep). There are interesting particulars in Langenbeck's description and discussion. The publication happened at the same time as that by Johann Lukas Schoenlein about fungi as the cause of the favus lesions. In this time Langenbeck lived at Göttingen. Later he went to Kiel and Berlin and became one of the most prominent surgeons of the 19th century. He sponsored the founding of the German Surgical Society, the Berlin Medical Society and the 'Archiv für Klinische Chirurgie'. In 1864 he was ennobled. Some of his assistants were Th. Billroth, R.U. Kroenlein, F. von Esmarch, and F. Trendelenburg.

Adhesion and cell-surface-hydrophobicity of sequentially isolated genetic isotypes of Candida albicans in an HIV-infected Southern Chinese cohort.

Objectives of the study were to investigate the variability in yeast adhesion and cell-surface-hydrophobicity (CSH) during human immunodeficiency virus (HIV) disease progression, using a total of 60 sequential Candida albicans isolated from oral rinse samples of seven HIV-infected individuals with (4) and without (3) clinical symptoms of oropharyngeal candidosis. Significant differences in the adhesion to buccal epithelial cells (BECs) during sequential visits were observed for all genetic isotypes in five of the seven individuals and three isotypes belonging to the sixth individual. A single isotype of patient HK1 and another of HK4 (genotype I) demonstrated significant variations in their CSH during sequential visits whereas no such differences were noted for the remaining genotypes. On Spearman correlation analysis an isotype from HK1 demonstrated a significant increased adherence to BECs and CSH during HIV disease progression whereas no such correlation was noted for the remaining isotypes studied. No significant differences in adherence to BECs or CSH values were observed between the symptomatic oral candidosis and the asymptomatic carrier group. Further, on regression analysis only the single isotype of HK1 demonstrated a significant positive correlation between adherence to BECs and CSH whereas no such correlation was observed when all tested Candida isolates were pooled and evaluated as a single, large group.

ITRACONAZOLE SOLUTION: SUMMARY OF PHARMACOKINETIC FEATURES AND REVIEW OF ACTIVITY IN THE TREATMENT OF FLUCONAZOLE-RESISTANT ORAL CANDIDOSIS IN HIV-INFECTED PERSONS

The clinical pharmacology of itraconazole is presented in relation to its use in the treatment of fluconazole-resistant oropharyngeal candidosis. The oral solution is a new formulation of itraconazole in which itraconazole is solubilised with the use of cyclodextrin. This formulation has a higher bioavailability and leads to higher local concentrations in the oral cavity which are advantages over the solid capsule formulation. Literature, in which the use of itraconazole oral solution was described to treat fluconazole-resistant oral candidosis, is reviewed. In about 55% of the patients signs and symptoms of oral candidosis were resolved after treatment with itraconazole oral solution. Although all the reviewed studies lack data to objectively qualify all the included patients as having a fluconazole-resistant candidosis, the authors conclude, that based on the available information itraconazole oral solution 100 or 200 mg twice daily can be effective for fluconazole-resistant oropharyngeal candidosis (OPC) and should be considered prior to salvage therapy with intravenous amphotericin B. The use of itraconazole, however, requires careful monitoring of the patients co-medication for potential serious drug-drug interactions.

Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis.

Molecular mechanisms of azole resistance in Candida albicans include alterations in the target enzyme and increased efflux of drug, but the impact of specific treatment regimens on resistance has not been established. A patient with advanced AIDS was enrolled in a longitudinal study to receive continuous oral fluconazole (FLU) 200 mg/day for the treatment of oropharyngeal candidosis (OPC). Oral cultures were obtained at time of enrollment, during episodes of OPC and quarterly for surveillance. The patient had five symptomatic relapses on continuous FLU during 43 months. All OPC episodes were successfully treated with increasing doses of FLU although increased FLU MICs were detected for C. albicans isolates with progression of time. DNA-typing techniques demonstrated that resistance developed in a persistent strain of C. albicans. Both FLU-resistant and isogenic isolates with reduced susceptibility were detected in the same clinical samples through multiple episodes. Analysis of molecular mechanisms of resistance revealed overexpression of MDR and CDR genes encoding efflux pumps (but not ERG11) in isolates with decreased FLU susceptibility. In addition, the presence of the G464S amino acid substitution in their lanosterol demethylase, affecting its affinity for FLU, was also detected. However, other isogenic, but FLU-susceptible isolates recovered from the same samples did not harbour the mutation, indicating microevolution of yeast populations within the oral cavity. In this patient, the continuous antifungal pressure exerted by FLU resulted in development of resistance of multifactorial nature. Despite their clonal origin, different subpopulations of C. albicans demonstrated distinct resistance mechanisms, including concomitant presence and absence of functional point mutations in ERG11 genes.

Growth Inhibition Effect of Brazilian Cerrado Plant Extracts on Candida Species

Ethanol extracts from leaves of Annona crassiflora and A. coriacea, and the fruits of Solanum lycocarpum and S. grandiflorum were investigated against 52 strains of Candida albicans, four strains of C. tropicalis and three strains of C. krusei isolated from human immunodeficiency virus-infected individuals with oropharyngeal candidosis, using the agar dilution method. Among the extracts tested, leaves of A. crassiflora was active against all the microorganisms and showed the greatest antifungal activity based on the MIC values. It was observed that 57 strains (96%) were inhibited by the extract from A. crassiflora at a concentration of 64 µg/ml, whereas against 18 strains (30%), it exhibited MIC values as low as 0.5 µg/ml against 10 6 UFC/ml organisms. Candida albicans CBS 562, a reference strain used as a control, showed a similar inhibition pattern. The activities of fluconazole, itraconazole, and ketoconazole were also evaluated and afforded MIC values = 32 µg/ml (19.5% of all strains), = 64 µg/ml (13.6%), and = 128 µg/ml (32.2%), respectively.

Therapeutic experience with fluconazole in the treatment of fungal infections in diabetic patients.

Diabetes mellitus is associated with a higher incidence of certain infections, including fungal infections like rhinocerebral zygomycosis (RCZ) and cutaneous candidosis. As the pathophysiology of increased susceptibility to infection of diabetic patients is very complex, a general therapeutic approach is not existing yet. Appropriate diabetes control remains as the best preventive measure. Nevertheless, effective drug therapy is very often required. Fluconazole has proven efficacy in prophylaxis, treatment and suppressive therapy of both systemic and superficial fungal infections, especially in candidosis and cryptococcosis. Therefore it is used routinely against fungal infections in diabetes (FID). Clinical efficacy of fluconazole against cutaeneous candidosis, oropharyngeal candidosis (OPC) and vulvovaginal candidosis (VVC) has been confirmed in more than 100 studies, involving more than 10.000 patients (pts). The overall success rate is 90%, with a mean dosage of 100-200 mg/d. In severe cases, e.g. in OPC in late-stage AIDS pts or in recurrent VVC, higher dosages of up to 800mg/d may be required. In the treatment of RCZ, therapeutic experience with fluconazole is limited1,2 . Four diabetic pts have been treated with dosages of 200-300 mg/d and all of them recovered. Nevertheless, treatment of RCZ should include surgical debridement combined with aggressive antifungal therapy. In conclusion, proven efficacy and the excellent safety profile justify the routine use of fluconazole in the treatment of FID.

Adhesion of oral Candida species to human buccal epithelial cells following brief exposure to nystatin.

Opportunistic oral infections caused by Candida albicans and non-albicans Candida species are particularly common in compromised patients. Nystatin, which belongs to the polyene group of antimycotics, is frequently used as a topical agent in the treatment of oro-pharyngeal candidosis. It is recognized that due to the delivery mode of nystatin (i.e. topical, intermittent), as well as the cleansing effect of saliva within the oral environment, the yeasts undergo a relatively brief exposure to this drug during treatment. Nevertheless, there is a sparsity of data on the effect of such brief exposure to nystatin on the pathogenic attributes of Candida such as their adherence to host surfaces. The adhesion of microbes to host mucosal surfaces is a major determinant of successful colonization and infection. Thus the main aim of our investigation was to compare the in vitro adhesion of 30 oral isolates of Candida belonging to six different species (comprising Candida albicans, Candida tropicalis, Candida glabrata, Candida guilliermondii, Candida krusei and Candida parapsilosis) to human buccal epithelial cells, following their brief exposure (1 h) to minimum inhibitory concentration of nystatin, and subsequent removal of the drug. The adhesion of these isolates to buccal epithelial cells was assessed by a previously described adhesion assay. Compared with the controls, there was a significant reduction in buccal epithelial cell adhesion of all six Candida species after drug exposure (54%-68%). However the adhesion of C. albicans isolates was the least affected by nystatin exposure, which was significantly different from that of the non-albicans species. These findings imply that sub-therapeutic levels of nystatin, which are likely to persist in the oral cavity during dosing intervals, may also be beneficial, as they inhibit candidal colonization. The significant difference in nystatin-induced suppression of adhesion between C. albicans and the non-albicans species investigated is a further testimonial for the pre-eminent virulence of the former species.