A Comparison of Triamcinolone Acetonide Econazole Cream and Nystatin Suspension in Treatment of Otomycosis.

OBJECTIVES/HYPOTHESIS: To compare the efficacy and adverse effects of triamcinolone acetonide econazole cream and nystatin suspension in the treatment of otomycosis, and to determine the clinical features, predisposing factors, and etiology of otomycosis. STUDY DESIGN: A prospective study. METHODS: A prospective clinical trial was conducted on 786 patients diagnosed with otomycosis. The study population was randomly divided into two treatment groups of triamcinolone acetonide econazole cream (TAEC) and nystatin suspension in a 1:1 ratio. After clearing all fungal deposits in the external auditory canal, the antimycotic drugs were locally applied for at least 2 weeks. The efficacy and adverse effects were compared between the two antifungal reagents by statistical analysis. Meanwhile, patient clinical data were collected to find out the clinical features, predisposing factors, and etiology. RESULTS: Pruritis was the most common symptom and Aspergillus niger was the leading fungal pathogen. There was high association (44.5%) of otomycosis with a history of unclean ear picking. The cure rate was 97.6% in the TAEC group and 73.5% in the nystatin group (P < .01). Treatment with TAEC resulted in 2.4% of patients complaining of discomforts (irritant dermatitis, otalgia, or headache) versus 59.8% of patients complaining discomforts treated with nystatin (P < .01). The residue rate of antifungals was 1.9% in the TAEC group and 89.9% in the nystatin group (P < .01) at the end of treatment. CONCLUSIONS: Thoroughly cleaning of the external auditory canal followed by local use of TAEC under endotoscope is an effective, convenient, and well-tolerated treatment for otomycosis. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:E1640-E1646, 2021.

Ultrasound-Assisted Preparation of Exopolysaccharide/Nystatin Nanoemulsion for Treatment of Vulvovaginal Candidiasis.

PURPOSE: As one of the classic anti-Canidia albicans (CA) and vulvovaginal candidiasis (VVC) drugs, nystatin (NYS) is limited by poor water solubility and easy aggregation. Traditional NYS vaginal delivery formulations do not fully adapt to the specific environment of the vaginal cavity. The use of exopolysaccharides (EPS) has great application potential in emulsifiers, but its use has not been reported in nanoemulsions. In this work, an EPS/NYS nanoemulsion (ENNE) was developed to improve the activities of NYS against CA and VVC. METHODS: The ENNE was prepared by ultrasonic method using EPS as an emulsifier, liquid paraffin oil as an oil phase, PEG400 as a co-emulsifier, and NYS as the loaded drug. ENNE preparation was optimized by response surface method. After optimization, in vitro and in vivo analysis of the anti-CA activity; animal experiments; staining with propidium iodide (PI), periodic acid-schiff (PAS), and hematoxylin-eosin (H&E); and cytokine experiments were performed to investigate the therapeutic ability against VVC. RESULTS: The optimal formulation and preparation parameters of ENNE were determined as follows: EPS content of 1.5%, PEG400 content of 3.2%, NYS content of 700 µg/mL, paraffin oil content of 5.0%, ultrasonic time of 15 min, and ultrasonic amplitude of 35%. The ENNE showed an encapsulated structure with an average particle size of 131.1 ± 4.32 nm. ENNE exhibited high storage and pH stability, as well as slow release. The minimum inhibitory concentration (MIC) of ENNE against CA was only 0.125 µg/mL and the inhibition zone was 19.0 ± 0.5 mm, for greatly improved anti-CA effect. The prepared ENNE destroyed the membrane of CA cells, and exhibited good anti-CA effect in vivo and therapeutic ability against VVC. CONCLUSION: The results of this study will promote the application of EPS in nanotechnology, which should lead to new and effective local drug formulations for treating VVC.

Efficacy of Topical Antimicrobial Agents Against Bacterial Isolates From Burn Wounds.

Topically applied antimicrobials are key to the prevention of infection and mortality in the acute burn population. The purpose of this study was to determine the in vitro effectiveness of commercially available topical antimicrobials, as well as topical preparations that were compounded in our burn care institution. One-hundred twenty microorganisms were tested against these topical antimicrobials and in vitro effectiveness was observed. Results showed that compounded preparations of 1:1:1 + Double Antibiotic (1 part bacitracin: 1 part silver sulfadiazine: 100,000 units/g nystatin + 5 mg/g neomycin sulfate + 500 units/g polymyxin B) and 3:1 + Double Antibiotic (3 part bacitracin: 1 part silver sulfadiazine + 5mg/g neomycin sulfate + 500 units/g polymyxin B) were effective against 100% of the isolates tested. Other topical agents showed moderate effectiveness, thus demonstrating the need for multiple topical agents to reach a broad spectrum of microorganisms. However, the development of topical antimicrobial resistance needs further study.

Formulation, characterization and in vitro evaluation of antifungal activity of Nystatin micro emulsion for topical application.

The current research aims at development and assessment of o/w nystatin microemulsion. The pseudoternary phase diagrams were developed to determine microemulsion existence regions by water titration method. Nystatin was liquefied in the blend of oil phase, surfactant and cosurfactant. Microemulsion was made by deliberate mixing of water and stirring in this blend. The S-mix (surfactant-cosurfactant mixtures) of the ratio 1:2 was found better than 1:1 and 2:1 S-mix ratios. In vitro permeation studies by Franz diffusion cell revealed faster rate of nystatin release from such microemulsion (5.37µg/cm2/h) as compared to nystrin (4.79µg/cm2/h), a commercially available aqueous suspension. Kinetic modeling demonstrated zero order drug release and release mechanism found to be anomalous i.e. superposition of dispersion and swelling controlled drug release. Antifungal activity was performed using well diffusion method in vitro against Candida albicans cultures grown on Sabouraud's dextrose agar. The results also confirmed the high diffusion rate of drug from microemulsion as compared to aqueous suspension. The outcomes of this study propose that topical microemulsion of nystatin provides better antifungal activity as compared to emulsion gels or aqueous suspensions.

Cutaneous candidiasis - an evidence-based review of topical and systemic treatments to inform clinical practice.

Cutaneous candidiasis is a common skin disease, and several treatments have been investigated within the last fifty years. Yet, systematic reviews are lacking, and evidence-based topical and systemic treatment strategies remain unclear. Thus, the aim of this review was to summarize efficacy and adverse effects of topical and oral therapies for cutaneous candidiasis in all age groups. Two individual researchers searched PubMed and EMBASE for 'cutaneous candidiasis' and 'cutaneous candidiasis treatment', 'intertrigo', 'diaper dermatitis' and 'cheilitis'. Searches were limited to 'English language', 'clinical trials' and 'human subjects', and prospective clinical trials published in abstracts or articles were included. In total, 149 studies were identified, of which 44 were eligible, comprising 41 studies of 19 topical therapies and four studies of three systemic therapies for cutaneous candidiasis. Topical therapies were investigated in infants, children, adolescents, adults and elderly, while studies of systemic therapies were limited to adolescents and adults. Clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated similar efficacy with complete cure rates of 73%-100%. Single-drug therapy was as effective as combinations of antifungal, antibacterial and topical corticosteroid. Four studies investigated systemic therapy, and oral fluconazole demonstrated similar efficacy to oral ketoconazole and topical clotrimazole. Limitations to this review were mainly that heterogeneity of studies hindered meta-analyses. In conclusions, clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated equal good efficacy and mild adverse effects similar to combinations of antifungal, antibacterial and topical corticosteroids. Oral fluconazole was as effective as topical clotrimazole and is the only commercially available evidence-based option for systemic treatment of cutaneous candidiasis.

Effects of Streptococcus salivarius K12 with nystatin on oral candidiasis-RCT.

OBJECTIVE: To evaluate the efficacy and safety of Streptococcus salivarius K12 as an adjuvant in treating oral candidiasis. METHODS: A total of 56 patients were participated in the randomized, double-blinded, placebo-controlled clinical trial. The S. salivarius K12 or placebo lozenges plus nystatin tablets were given for up to 4 weeks at 1-week interval and then followed up for 1 week thereafter. We collected and analyzed the mycological and clinical data, treatment course, and safety data. RESULTS: At the end of the treatment, significant differences were found in the mycological cure rates between K12 group and control group (90.48% and 55.56%, respectively, p = 0.008). Survival analysis demonstrated no statistical difference in overall cure rates comprehensively considering mycological cure, clinical improvement, and recurrence (p = 0.078), while statistical difference was found in mycological cure (p = 0.013) between the two groups. The median treatment courses of K12 group and control group were 3 weeks and 4 weeks, respectively. No severe events were reported during the study. CONCLUSION: Streptococcus salivarius K12 exhibited potential efficacy and safety as an adjuvant in treating oral candidiasis by enhancing mycological cure and shortening the treatment course of conventional antifungal therapy in this randomized, double-blinded, placebo-controlled clinical trial. Further large-scale clinical studies are desired to accumulate more evidence for its clinical applications.

Comparison of the efficacy of indocyanine green-mediated photodynamic therapy and nystatin therapy in treatment of denture stomatitis.

BACKGROUND: Candida species have an influence in the pathogenesis of denture stomatitis. The current study aimed to investigate the efficacy of indocyanine green (ICG)-mediated photodynamic therapy (PDT) in combination with nystatin mouthwash (PDT + nystatin) for the treatment of denture stomatitis in comparison with routine antifungal therapy with nystatin alone. METHODS: In this double-blind randomized clinical trial, 66 patients were randomly assigned into PDT + nystatin (n = 33) and nystatin (n = 33) groups, both groups were treated 3-times a day (15 days) with nystatin mouthwash, and PDT was performed twice once a week for the PDT + nystatin group. Briefly, ICG was applied on the palatal lesion and laser irradiation was performed using a diode laser (810 nm, 56 J/cm2). Nystatin group was also treated with sham laser in order to eliminate the possible psychological effects. The clinical and mycological evaluations were carried out at the baseline, during treatment, and the end of follow-up. Patients who completed the treatment and follow-up were eligible for statistical analysis (each group 28 cases). RESULTS: Patient treatment with nystatin or PDT + nystatin reduced the lesions extension. Candida species were isolated from all patients and the number of Candida CFU in both groups showed a significant reduction at each post-treatment visit; however, the mean reduction achieved in the PDT + nystatin group was significantly higher than nystatin alone. CONCLUSIONS: ICG-mediated PDT in combination with nystatin mouthwash can improve the clinical feature of denture stomatitis with no adverse effects; therefore, it could be used as an alternative to the currently available antifungal therapy using nystatin alone.

Combined vaginal administration of nystatin, diiodohydroxyquin, and benzalkonium chloride versus oral metronidazole for the treatment of bacterial vaginosis.

OBJECTIVE: To compare combined vaginal administration of nystatin, diiodohydroxyquin, and benzalkonium chloride versus oral metronidazole for the treatment of bacterial vaginosis (BV). METHODS: A randomized controlled trial was conducted among women diagnosed with BV using the Amsel criteria (n=90) at a university hospital in Khon Kaen, Thailand, between June 27, 2017, and April 30, 2018. The oral metronidazole group (n=44) received 400 mg of metronidazole, administered three times per day. The combined vaginal tablet group (n=46) received a vaginal suppository once daily, which comprised nystatin (100 000 U), diiodohydroxyquin (100 mg), and benzalkonium chloride (7 mg). Treatment was administered for 7 days in both groups. Follow-up visits at 14 and 42 days assessed treatment outcomes and adverse effects. RESULTS: Remission of BV occurred among 41 (93%) women in the oral metronidazole group and 39 (85%) women in the combined vaginal tablet group. The adjusted relative risk was 0.92 (95% confidence interval 0.80-1.06). The rate of nausea and/or vomiting was significantly higher in the oral metronidazole group than that in the combined vaginal tablet group. CONCLUSION: Treatment efficacy of the combined vaginal tablet versus oral metronidazole was equivalent. CLINICAL TRIAL REGISTRATION: TCTR20170627001 (www.clinicaltrials.in.th).

PRISM study: Comparison of a nystatin-neomycin-polymyxin B combination with miconazole for the empirical treatment of infectious vaginitis.

OBJECTIVE: An empirical treatment of infectious vaginitis is justified because of its multiple etiologies, the frequent uncertainty of clinical diagnosis and limits of microbiological analysis. Our aim was to comparatively investigate nystatin-neomycin-polymyxin B combination (NNP, Polygynax®) and miconazole. PATIENTS AND METHODS: In this European multicenter, double-blind PRISM trial, participating women presenting with infectious vaginitis were randomized to receive one vaginal capsule containing either NNP for 12 days or miconazole for 3 days followed by 9 days of placebo. RESULTS: The clinical success rate was higher in the NNP group (n=302) than the miconazole group (n=309), with a difference between groups close to statistical significance (91.1% vs. 86.7%, P=0.0906). The risk of treatment failure was 36% lower in the NNP group (odds ratio, 0.64; 95% confidence interval, 0.38-1.07). Vaginal burning on Day 2 and vaginal discharge on Day 4 were significantly less intense in the NNP group than in the miconazole group (39.1 vs. 42.3, P=0.031 and 34.6 vs. 37.6, P=0.031, respectively). Adverse drug reactions were reported by 1.2% and 2.1% of patients in the NNP and miconazole group respectively, with the ratio of adverse drug reactions relative to total adverse events significantly higher in the miconazole group (20.3% vs. 6.9%, P=0.022). CONCLUSION: The widespread use of NNP for several decades and its good efficacy and safety profile, as well as the frequent diagnostic uncertainties due to the various pathogens sustain the initiation of this broad-spectrum empirical treatment in infectious vaginitis.

Nystatin antifungal micellar systems on endotracheal tubes: development, characterization and in vitro evaluation.

Decontamination of patients' clinical devices in intensive care units is generally performed with an antifungal suspension. Nystatin is a widely-used high spectrum antifungal due to its low systemic absorption. However, nystatin has high hydrophobicity which hinders the contact with the internal lumen of the devices. In this work, hydrophilic micellar systems of nystatin were developed with sodium deoxycholate on silicone endotracheal tubes. The physical characteristics of the micellar system at different nystatin:deoxycholate ratios were studied using scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. The electron microscopy results reveal that the deoxycholate micellar system altered the surface morphology, and the size of the aggregates was observed to be smaller. The hydrophilic structures of deoxycholate produce systems with a high surface area containing nystatin molecules on their interior. The X-ray and differential scanning calorimetry assays revealed a typical change in the crystallinity of micellar systems when the deoxycholate proportion increases. The endothermic peak of nystatin was not observed in the micellar systems as a consequence of the reduced crystallinity. Nystatin was homogenously dispersed in the surfactant matrix. Micellar systems with 1:0.8 nystatin:deoxycholate ratio (MS-N:DC [1:0.8]) showed increased antifungal activity compared to nystatin raw material. Micellar systems also achieved an over 40% inhibition of Candida albicans biofilm formation. The results obtained in this study conclude that the higher hydrophilic characteristic of the surfactant deoxycholate enhances nystatin penetration into the surface of the endotracheal tubes.

In vivo biocompatibility of an interim denture resilient liner containing antifungal drugs.

STATEMENT OF PROBLEM: Antifungal agents incorporated into interim denture resilient liners have been suggested as an adjunct treatment for denture stomatitis (DS). However, before applying this protocol to humans, biocompatibility analysis of such drugs in animal models is required. PURPOSE: The purpose of this animal study was to evaluate the in vivo biocompatibility of an interim resilient liner modified with minimum inhibitory concentrations (MICs) of antifungal drugs for Candida albicans biofilm. MATERIAL AND METHODS: Sixty Wistar rats were divided into 6 groups (n=5): PC=positive control/no protocol; IOD (intraoral device)=rats using an acrylic resin palatal device (PD); Tru=rats using a PD relined with Trusoft; and Ny (nystatin), Chx (chlorhexidine diacetate), and Ke (ketoconazole) groups=rats using a PD relined with Trusoft + drug MICs. The rats were sacrificed at 7 or 14 days of trial. Histopathological qualitative analysis was performed by comparing photomicrographs of histological sections of the intermolar region. Morphological changes in the epithelium and keratin were quantitatively analyzed by computerized planimetry, and data were analyzed by using 2-way ANOVA and the Tukey HSD test (α=.05). RESULTS: Quantitative analysis showed that only PD containing Ke significantly decreased the thickness and area of the keratin compared with the other groups (P<.001), which showed no differences between each other (P>.05). These results agreed with those of qualitative analysis. CONCLUSIONS: Incorporation of MICs of Ny and Chx in Trusoft did not induce histopathological changes in the rat palatal mucosa, suggesting the in vivo biocompatibility of this DS treatment.

Influence of subinhibitory antifungal concentrations on extracellular hydrolases and biofilm production by Candida albicans recovered from Egyptian patients.

BACKGROUND: Extracellular hydrolases (phospholipase, aspartyl protease and haemolysin) and biofilm production are considered as major virulence factors of the opportunistic pathogenic fungus Candida albicans. However, the impact of antifungal therapy on such virulence attributes is not well investigated. The common antifungal agents may disturb the production of secreted hydrolases as well as biofilm formation. Accordingly, this study addressed the effect of subinhibitory concentrations (sub-MICs) of selected antifungal agents on some virulence factors of C. albicans clinical isolates. METHODS: C. albicans isolates (n = 32) were recovered from different clinical samples and their identification was confirmed to the species level. Antifungal susceptibility profiles of isolates were determined against (nystatin, fluconazole and micafungin) and minimum inhibitory concentrations (MICs) were interpreted according to Clinical and Laboratory Standards Institute guidelines. Virulence determinants comprising secreted hydrolases (phospholipase, aspartyl protease and haemolysin) and biofilm formation were investigated in the presence of the sub-MICs of the tested antifungal agents. RESULTS: Treatment of clinical C. albicans isolates with subinhibitory nystatin, fluconazole and micafungin concentrations significantly decreased production of extracellular hydrolases. Nystatin had the greatest inhibitory effect on phospholipase and aspartyl protease production. However, micafungin showed the highest reducing effect on the hemolytic activity of the treated clinical isolates. Moreover, nystatin and micafungin, but not fluconazole, had a noticeable significant impact on inhibiting biofilm formation of C. albicans clinical isolates. CONCLUSION: Our findings highlighted the significant influences of commonly prescribed antifungal agents on some virulence factors of C. albicans. Accordingly, antifungal therapy may modulate key virulence attributes of C. albicans.

Effectiveness and Pharmacokinetic evaluation of Geonistin® (Oxytetracyline and Nystatin) Vaginal Tablets for Unspecific and Mixed Vulvovaginal Infections (GENIE Study).

The GENIE study was performed to evaluate the effectiveness and systemic exposure to oxytetracycline in local treatment of unspecific and mixed vulvovaginal infections characterized by vaginal discharge with Geonistin® vaginal tablets (100 mg oxytetracycline and 100 000 IU nystatin). The total number of subjects enrolled was 189. The treatment had beneficial effects in 100% of the study population. According to the Nugent score, the treatment had a positive effect in 89.2% of participants. The microbiological cure rate was 78.8%. Oxytetracycline concentration levels were from 13.3 to 32.2 ng/mL in 11 out of 15 subjects, and in four subjects the levels were below 10 ng/mL. Geonistin® had a beneficial effect on the unspecific and mixed vulvovaginal infections characterized by vaginal discharge in all efficacy and safety outcomes. Microbiological and the Nugent score efficacy measures confirmed clinical effectiveness. Beneficial efficacy results were achieved with only a few non-serious adverse events.

Diversity, frequency and antifungal resistance of Candida species in patients with type 2 diabetes mellitus.

OBJECTIVE: To determine number, species of Candida and Candida resistance to antifungal therapy according to the metabolic control state and the associated salivary changes in patients with type 2 diabetes mellitus (DM2). MATERIALS AND METHODS: Samples of non-stimulated saliva were collected from 52 patients with DM2. Salivary pH was measured and cultured on Sabouraud glucose agar and the values of CFU/ml were calculated. The species were presumptively identified using CHROMagar Candida® plates, and identification was confirmed by polymerase chain reaction (PCR). C. albicans isolates were cultured on SGA tetracycline agar with nystatin and fluconazole diffusion disks to measure susceptibility. RESULTS: Sixty six percent of the yeasts isolated were Candida albicans, followed by C. glabrata (20.7%). In patients with decompensated DM2, there was an inverse association between HbA1c value and salivary pH. At higher levels of salivary acidification, a greater diversity and quantity of yeasts of the genus Candida were observed. With nystatin, higher inhibition was observed at lower pH. CONCLUSIONS: The antifungal therapies could be more effective if it consider, qualitative salivary characteristics as pH, that could determine the susceptibility of species of Candida to at least to nystatin, which is the most used antifungal for treatment to oral candidiasis in patients with DM2.

A Drug-drug Interaction Between Cyclosporine and Nystatin.

We present a case of increased cyclosporine concentration and liver function right after the combinational use of cyclosporine and nystatin, which indicated a drug-drug interaction between them. Both the concentration and liver function were decreased after discontinuation of nystatin and remained normal after taking on cyclosporine again. To our knowledge, this is the first case report of the interactions between nystatin and cyclosporine. Enteric P-glycoprotein could play an important role in the pharmacokinetic profile of cyclosporine, which needs further identification by physicians and pharmacists.

Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin.

To promote transungual permeation of nystatin (NYST), molecule with high molecular weight, no water-soluble, amphoteric by iontophoresis. The synergic effect of the combination of cetylpyridinium chloride, CPC, or polyoxyethylene (20) sorbitan monooleate, TW80, and iontophoresis was investigated. In vitro permeation experiments were carried out through bovine hoof slices using vertical diffusion cells. A low current density (0.2 mA/cm2) was applied by introducing Ag/AgCl electrodes in the donor (anode) and receptor (cathode) chambers. The donor phase consisted of a solution, a suspension, or gel-type vehicles containing NYST and surfactants in pH 5.6 HEPES buffer. The addition of CPC to NYST suspension (SOSP) produced a fivefold increase on the permeability of the bovine hoof membrane to the drug. The application of anodal iontophoresis further improved NYST flux. Conversely, NYST transungual permeation was not influenced by TW80 either in the passive diffusion or iontophoretic flux. Furthermore, the iontophoretic treatment does not appear to induce irreversible alterations to the hoof bovine membranes. The present work demonstrated the efficacy of iontophoresis as a treatment for different nail pathologies with large molecules very slightly soluble in water without irreversibly affecting the nail structure. A synergistic effect between CPC and iontophoresis was observed.