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1.
BMC Infect Dis ; 19(1): 54, 2019 Jan 16.
Article in English | MEDLINE | ID: mdl-30651066

ABSTRACT

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.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Candida albicans/metabolism , Hydrolases/metabolism , Virulence Factors/metabolism , Antifungal Agents/administration & dosage , Aspartic Acid Proteases/metabolism , Biofilms/drug effects , Candida albicans/isolation & purification , Candida albicans/pathogenicity , Egypt , Fluconazole/pharmacology , Fungal Proteins/metabolism , Humans , Micafungin/administration & dosage , Micafungin/pharmacology , Microbial Sensitivity Tests , Nystatin/administration & dosage , Nystatin/pharmacology , Phospholipases/metabolism
2.
Oral Dis ; 25(6): 1573-1580, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31177581

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Candida albicans/drug effects , Candidiasis, Oral/drug therapy , Candidiasis, Oral/therapy , Nystatin/administration & dosage , Nystatin/therapeutic use , Probiotics/administration & dosage , Administration, Oral , Anti-Bacterial Agents/adverse effects , Candidiasis, Oral/microbiology , Double-Blind Method , Humans , Nystatin/adverse effects , Probiotics/adverse effects , Recurrence , Streptococcus salivarius
3.
J Eur Acad Dermatol Venereol ; 33(10): 1863-1873, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31287594

ABSTRACT

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.


Subject(s)
Antifungal Agents/therapeutic use , Candidiasis, Cutaneous/drug therapy , Clotrimazole/therapeutic use , Fluconazole/therapeutic use , Miconazole/therapeutic use , Nystatin/therapeutic use , Administration, Oral , Administration, Topical , Antifungal Agents/administration & dosage , Clotrimazole/administration & dosage , Drug Therapy, Combination , Evidence-Based Medicine , Fluconazole/administration & dosage , Humans , Ketoconazole/therapeutic use , Miconazole/administration & dosage , Nystatin/administration & dosage
4.
J Prosthet Dent ; 121(1): 135-142, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30646999

ABSTRACT

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.


Subject(s)
Antifungal Agents/administration & dosage , Candida albicans/drug effects , Denture Liners , Mouth Mucosa/drug effects , Acrylic Resins , Analysis of Variance , Animals , Biofilms/drug effects , Chlorhexidine/administration & dosage , Keratins/drug effects , Ketoconazole/administration & dosage , Materials Testing , Microbial Sensitivity Tests , Mouth Mucosa/cytology , Nystatin/administration & dosage , Rats , Rats, Wistar
5.
Pharmazie ; 74(1): 34-38, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30782248

ABSTRACT

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.


Subject(s)
Antifungal Agents/administration & dosage , Candida albicans/drug effects , Deoxycholic Acid/chemistry , Nystatin/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Biofilms/drug effects , Calorimetry, Differential Scanning , Crystallization , Hydrophobic and Hydrophilic Interactions , Intubation, Intratracheal/instrumentation , Micelles , Microscopy, Electron, Scanning , Nystatin/chemistry , Nystatin/pharmacology , Silicones/chemistry , Surface-Active Agents/chemistry , X-Ray Diffraction
6.
Pak J Pharm Sci ; 32(4): 1671-1677, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31608889

ABSTRACT

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.


Subject(s)
Antifungal Agents/pharmacology , Emulsions/chemistry , Emulsions/pharmacology , Nystatin/pharmacology , Administration, Topical , Antifungal Agents/administration & dosage , Antifungal Agents/chemistry , Antifungal Agents/pharmacokinetics , Candida albicans/drug effects , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Evaluation, Preclinical , Drug Liberation , Emulsions/administration & dosage , Emulsions/pharmacokinetics , Excipients/chemistry , Hydrogen-Ion Concentration , Nystatin/administration & dosage , Nystatin/chemistry , Nystatin/pharmacokinetics , Solubility , Surface-Active Agents , Viscosity
7.
Acta Odontol Scand ; 76(8): 580-586, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30045641

ABSTRACT

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.


Subject(s)
Antifungal Agents/administration & dosage , Candida albicans/isolation & purification , Candidiasis, Oral/drug therapy , Diabetes Mellitus, Type 2/microbiology , Drug Resistance, Fungal , Adult , Candida/classification , Candida albicans/drug effects , Candida glabrata/isolation & purification , Candidiasis, Oral/microbiology , Female , Fluconazole/administration & dosage , Humans , Microbial Sensitivity Tests , Nystatin/administration & dosage
8.
AAPS PharmSciTech ; 19(4): 1574-1581, 2018 May.
Article in English | MEDLINE | ID: mdl-29484614

ABSTRACT

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.


Subject(s)
Hoof and Claw/drug effects , Hoof and Claw/metabolism , Iontophoresis/methods , Nystatin/chemistry , Nystatin/metabolism , Administration, Cutaneous , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Cattle , Dose-Response Relationship, Drug , Excipients/administration & dosage , Excipients/chemistry , Excipients/metabolism , Nystatin/administration & dosage , Permeability/drug effects
9.
J Prosthodont ; 27(2): 177-181, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29135059

ABSTRACT

PURPOSE: To investigate the ultimate tensile strength of temporary soft denture liners modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm (SC5314) determined in previous microbiological research. MATERIALS AND METHODS: Dumbbell-shaped specimens (n = 7) with a central cross-sectional area of 6 × 3 × 33 mm were produced by Softone and Trusoft, without (control) or with incorporation of drugs in powder form at MICs for C. albicans biofilm (per g of material powder): nystatin (0.032 g), chlorhexidine diacetate (0.064 g), ketoconazole (0.128 g), miconazole (0.256 g), and itraconazole (0.256 g). After plasticization, specimens were immersed in distilled water at 37°C for 24 hours, 7 or 14 days, and then tested in tension in a universal testing machine at 40 mm/min. Data of tensile strength (MPa) and elongation percentage (%) were submitted to 3-way ANOVA and Tukey's test (α = 0.05). RESULTS: At the end of 14 days, the tensile strength for both materials was significantly lower in the groups modified by miconazole and itraconazole compared to the other groups (p < 0.0001), which showed no significant difference between them (p > 0.05). After 7 and 14 days in water, miconazole and itraconazole added into both materials resulted in significantly lower elongation percentages compared to the other antifungal agents and control (p < 0.0001), which were similar to each other (p > 0.05). CONCLUSIONS: The addition of the nystatin, chlorhexidine, and ketoconazole at MICs for C. albicans biofilm resulted in no harmful effects on the tensile strength and elongation percentage of the temporary soft denture liner materials up to 14 days.


Subject(s)
Antifungal Agents/adverse effects , Denture Liners , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Chlorhexidine/administration & dosage , Chlorhexidine/adverse effects , Chlorhexidine/pharmacology , Humans , Itraconazole/administration & dosage , Itraconazole/adverse effects , Itraconazole/pharmacology , Ketoconazole/administration & dosage , Ketoconazole/adverse effects , Ketoconazole/pharmacology , Miconazole/administration & dosage , Miconazole/adverse effects , Miconazole/pharmacology , Microbial Sensitivity Tests , Nystatin/administration & dosage , Nystatin/adverse effects , Nystatin/pharmacology , Tensile Strength/drug effects
10.
Clin Infect Dis ; 64(10): 1387-1395, 2017 May 15.
Article in English | MEDLINE | ID: mdl-28158439

ABSTRACT

BACKGROUND: Congenital cutaneous candidiasis (CCC) is a challenging diagnosis due to various rash presentations. Inadequate early treatment is associated with high rates of dissemination and death. The effects of early diagnosis, dermatologic presentation, and antifungal treatment on outcomes are lacking. METHODS: CCC cases were reviewed from 2 academic neonatal intensive care units (NICUs) from 2004 to 2015. We defined CCC as a diffuse rash involving the body, extremities, face or scalp, and/or funisitis, presenting in the first week (≤7 days), with identification of Candida species from skin or mucous membrane cultures, and/or by culture or staining of the placenta or umbilical cord. RESULTS: CCC occurred in 0.1% of all NICU admissions (21 of 19 303) and 0.6% of infants <1000 grams birth weight. Median gestational age of CCC infants was 26 3/7 (range, 23 0/7-40 4/7) weeks. Skin findings were commonly present on the day of birth [median (range): 0 (0-6) days], appearing most frequently as a desquamating, maculopapular, papulopustular, and/or erythematous diffuse rash. When systemic antifungal therapy was started empirically at the time of rash presentation and continued for a median (interquartile range) of 14 (14-15) days, all patients survived and none developed dissemination. Delaying systemic treatment, exclusive use of nystatin, and treating for <10 days was associated with Candida bloodstream dissemination. CONCLUSIONS: CCC is an invasive infection that presents as a diffuse rash in preterm and term infants. Prompt systemic antifungal treatment at the time of skin presentation for ≥14 days prevents dissemination and Candida-related mortality.


Subject(s)
Candidiasis, Cutaneous/congenital , Candidiasis, Cutaneous/drug therapy , Candidiasis/prevention & control , Infant, Premature, Diseases/drug therapy , Adolescent , Adult , Antifungal Agents/therapeutic use , Candida/drug effects , Candida/isolation & purification , Candidiasis/microbiology , Candidiasis, Cutaneous/blood , Candidiasis, Cutaneous/diagnosis , Drug Administration Routes , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature, Diseases/microbiology , Intensive Care Units, Neonatal , Male , Medical Records , Nystatin/administration & dosage , Nystatin/adverse effects , Nystatin/therapeutic use , Pregnancy , Skin/microbiology , Treatment Outcome , Young Adult
11.
Microb Pathog ; 107: 390-396, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28431915

ABSTRACT

BACKGROUND: Candida glabrata (C. glabrata) and C. krusei are now emerging as serious hospital acquired infections in immunocompromised patients. Menthol, a terpenic compound, has been reported to have antifungal activity. OBJECTIVES: The aim of this study was to investigate the effect of menthol in combination with itraconazole or nystatin against C. glabrata and C. krusei isolates. METHODS: The effects of menthol along with itraconazole and nystatin, were evaluated by the Clinical Laboratory Standards Institute (CLSI) M44-A and CLSI M27-A3 methods. The fractional inhibitory concentration index (FICI) was determined for menthol plus itraconazole and nystatin combinations using the checkerboard method. RESULTS: The mean of minimum inhibitory concentration (MIC) values of menthol, nystatin and itraconazole were 53.2, 2.30 and 1.50 µg/ml for C. glabrata isolates and 121, 1.08 and 0.38 µg/ml for C. krusei isolates, respectively. Menthol in combination with itraconazole or nystatin exhibited the synergistic effects against all species of Candida tested. FICI values for menthol plus itraconazole and nystatin combinations ranged from 0.250 to 0.561 and 0.139 to 0.623 for C. glabrata isolates, and 0.182 to 0.750 and 0.188 to 0.760 for C. krusei, respectively. CONCLUSIONS: These results support the potential use of menthol as an anticandidal agent, and it can be used complementarily with other conventional antifungal agents.


Subject(s)
Candida glabrata/drug effects , Candida/drug effects , Itraconazole/pharmacology , Menthol/pharmacology , Nystatin/pharmacology , Antifungal Agents/pharmacology , Candida/isolation & purification , Candida glabrata/isolation & purification , Drug Combinations , Drug Synergism , Female , Humans , Itraconazole/administration & dosage , Menthol/administration & dosage , Microbial Sensitivity Tests , Mouth/microbiology , Nystatin/administration & dosage , Vagina/microbiology
12.
Mycoses ; 60(12): 826-829, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28877374

ABSTRACT

Duration >120 minutes of extracorporeal circulation (ECC) during cardiopulmonary bypass procedure was associated to an increased risk of candidemia in the intensive care unit (ICU). To evaluate oral nystatin prophylaxis in cardiac surgery considering its exclusive effect on Candida, in the absence of systemic effects and selection of resistant strains to polyene. We conducted an observational study in the postcardiac surgery ICU of Policlinico "Umberto I" of Rome. From January 2014, all patients with a prolonged ECC >120 minutes were systematically treated with oral nystatin (Prophylaxis group). This group was compared with all patients hospitalised in the same ICU, who have not received oral nystatin after ECC >120 minutes (No prophylaxis group). Overall, 672 consecutive patients were analyzed: 318 (47.3%) patients belonged to the no prophylaxis group, and 354 (52.7%) patients to the prophylaxis group. Diagnosis of candidemia was confirmed in 7 (2.2%) patients, all belonged to the no prophylaxis group. At multivariate analysis, oral nystatin prophylaxis showed a protective effect for development of candidemia after cardiac surgery. Oral nystatin prophylaxis, in patients who underwent a ECC >120 minutes, seems to reduce development of candidemia; however, the real efficacy of such prophylaxis approach requires further investigation.


Subject(s)
Antifungal Agents/administration & dosage , Candidiasis/prevention & control , Cardiopulmonary Bypass/adverse effects , Extracorporeal Circulation/adverse effects , Nystatin/administration & dosage , Aged , Candida/classification , Candida/drug effects , Candida/genetics , Candida/isolation & purification , Candidiasis/drug therapy , Candidiasis/etiology , Candidiasis/microbiology , Female , Heart Diseases/surgery , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged
13.
Pharm Dev Technol ; 22(2): 266-274, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27499389

ABSTRACT

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.


Subject(s)
Antifungal Agents/administration & dosage , Candida albicans/drug effects , Candidiasis, Oral/drug therapy , Lidocaine/administration & dosage , Nystatin/administration & dosage , Stomatitis/drug therapy , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Drug Liberation , Hardness , Humans , Lidocaine/chemistry , Lidocaine/pharmacology , Nystatin/chemistry , Nystatin/pharmacology , Tablets
14.
J Oral Pathol Med ; 45(1): 35-40, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26058710

ABSTRACT

OBJECTIVES: Oral lichen planus (OLP) is an inflammatory disease with an unknown origin. Oxidative stress is suspected to play a role in its pathogenesis. The aim of this study was to evaluate serum levels of oxidative stress factors and C-reactive protein in patients with OLP. MATERIALS & METHODS: In this case-control study, 25 patients with OLP and 23 control subjects were enrolled. Serum levels of C-reactive protein (CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC) were investigated in both groups. In case group, all these factors were re-evaluated after 14 days of treatment. The characteristics of the lesions were also recorded at each visit. RESULTS: Serum levels of MDA were significantly higher (P = 0.009), and TAC was significantly lower (P < 0.001) in patients with OLP. There were no significant differences between serum levels of TAC, CRP, and MDA in patients with OLP before and after treatment (P = 0.174, P = 0.556, P = 0.194, respectively). However, the difference in serum levels of TAC between erosive and atrophic patients with keratotic OLP was significant (P = 0.024). CONCLUSION: We concluded patients with OLP have increased of serum MDA and the decrease of serum TAC compared with the healthy subjects, and 14-day treatment of OLP did not have any effect on serum levels of oxidative stress factors.


Subject(s)
C-Reactive Protein/metabolism , Lichen Planus, Oral/blood , Lichen Planus, Oral/drug therapy , Adult , Aged , Antioxidants/metabolism , Biomarkers/blood , Case-Control Studies , Dexamethasone/administration & dosage , Female , Humans , Male , Malondialdehyde/blood , Middle Aged , Mouthwashes/administration & dosage , Nystatin/administration & dosage , Oxidative Stress/physiology
16.
Oral Dis ; 22(8): 761-765, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27416928

ABSTRACT

OBJECTIVE: A retrospective case series published in 2012 concluded that miconazole and nystatin used as topical antifungal drugs appear to interact equally strongly with warfarin. If confirmed, this finding has significant implications for clinical practice. This study evaluates the evidence. MATERIALS AND METHODS: Evidence from the pharmacology literature, the medical literature and the 'yellow card' adverse drug reaction surveillance reports was analysed regarding possible interactions of nystatin and miconazole with warfarin. RESULTS: There is strong evidence to support the derangement of warfarin anticoagulation by miconazole oral gel in all areas of evidence studied. No postulated mechanism of interaction, no additional published reported cases and no supportive data from adverse drug reports were identified which would corroborate the case for a significant interaction between nystatin and warfarin. CONCLUSION: Miconazole and nystatin used as topical antifungal drugs do not interact equally strongly with warfarin. Miconazole oral gel can clearly interact with warfarin to cause derangement of anticoagulation. Nystatin appears unlikely to interact with warfarin.


Subject(s)
Anticoagulants/pharmacology , Antifungal Agents/pharmacology , Miconazole/pharmacology , Nystatin/pharmacology , Warfarin/pharmacology , Administration, Topical , Anticoagulants/therapeutic use , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Drug Interactions , Humans , International Normalized Ratio , Miconazole/administration & dosage , Miconazole/therapeutic use , Nystatin/administration & dosage , Nystatin/therapeutic use , Retrospective Studies , Warfarin/therapeutic use
17.
Int J Cancer ; 136(1): 182-94, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-24798787

ABSTRACT

Cetuximab, a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), has been intensively investigated as a promising cancer treatment strategy. The specific mechanism of cetuximab endocytosis and its influence on cetuximab uptake, biodistribution and efficacy still remain elusive. Recently, statins have been reported to synergize with EGFR-targeting agents. Our prior work established that nystatin, a cholesterol-sequestering antifungal drug, facilitates endocytosis via the clathrin-dependent pathway. This study aimed to investigate whether nystatin regulates the uptake and efficacy of cetuximab and cetuximab-based antibody-drug conjugates (cetuximab-ADCs). In vitro and in vivo efficacies of nystatin on the uptake and activity of cetuximab/cetuximab-ADCs were studied in multiple human carcinoma cell lines and xenograft models, respectively. We identified that cholesterol sequestration by nystatin enhanced cetuximab internalization in EGFR-positive carcinoma cells by regulating EGFR trafficking/turnover and facilitating a switch from lipid rafts to clathrin-mediated endocytosis. Combination treatment with cetuximab and nystatin selectively increased cetuximab uptake by tumor tissues, translating into potentiated antitumor efficacy of cetuximab in vivo (A431 and A549 tumors). Nystatin-enhanced internalization of cetuximab further improved the uptake and potency of cetuximab-doxorubicin and cetuximab-methotrexate conjugates in EGFR-positive cetuximab-resistant tumors. Combination therapy with nystatin plus either cetuximab or cetuximab-ADC further prolonged animal survival and significantly suppressed tumor growth, as compared with single-agent cetuximab or cetuximab-ADC. In summary, our results identify a novel mechanism whereby cholesterol sequestration enhances the uptake of EGFR-targeting mAb and ADCs, therefore providing preclinical proof-of-concept that combination with nystatin can potentiate the delivery and efficacy of these EGFR-targeted agents.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cholesterol/metabolism , Endocytosis , Animals , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Biological Transport , Cell Line, Tumor , Cetuximab , Doxorubicin/administration & dosage , Drug Resistance, Neoplasm/drug effects , Drug Synergism , ErbB Receptors/antagonists & inhibitors , Humans , Membrane Microdomains/metabolism , Mice, Inbred BALB C , Mice, Nude , Nystatin/administration & dosage , Tissue Distribution , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
18.
Parasitol Res ; 114(4): 1425-31, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25645004

ABSTRACT

The present study was conducted to evaluate the in vitro and in vivo antiparasitic efficacy of active compounds from the bacterial extracellular products of Streptomyces griseus SDX-4 against Ichthyophthirius multifiliis. Bioassay-guided fractionation and isolation of compounds with antiparasitic activity were performed on n-butanol extract of S. griseus yielding a pure bioactive compound, nystatin (Nys), identified by comparing spectral data (EI-MS, (1)H NMR, and (13)C NMR) with literature values. Results from in vitro antiparasitic assays revealed that Nys could be 100% effective against I. multifiliis theronts and encysted tomonts at the concentration of 6.0 mg L(-1), with the median effective concentration (EC50) values of 3.1 and 2.8 mg L(-1) for theronts and encysted tomonts (4 h), respectively. Results of in vivo test demonstrated that the number of I. multifiliis trophonts on the gold fish treated with Nys was markedly lower than the control group at 10 days after exposed to theronts (p < 0.05). In the control group, 85.7% mortality was observed owing to heavy I. multifiliis infection at 10 days after the exposure. On the other hand, only 23.8% mortality owing to parasite infection was recorded in the groups treated with the Nys (4.0 and 6.0 mg L(-1)). In addition, our results showed that the survival and reproduction of I. multifiliis tomont exited from the fish were significantly reduced after treated with the 6.0 mg L(-1) Nys. The median lethal dose (LD50) of Nys for goldfish was 16.8 mg L(-1). This study firstly demonstrated that Nys has potent antiparasitic efficacy against I. multifiliis, and it can be a good candidate drug for chemotherapy and control of I. multifiliis infections.


Subject(s)
Antiprotozoal Agents/administration & dosage , Ciliophora Infections/veterinary , Fish Diseases/drug therapy , Hymenostomatida/drug effects , Nystatin/administration & dosage , Streptomyces griseus/chemistry , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Ciliophora Infections/drug therapy , Ciliophora Infections/parasitology , Drug Evaluation , Fish Diseases/parasitology , Goldfish/parasitology , Hymenostomatida/physiology , Lethal Dose 50 , Nystatin/chemistry , Nystatin/isolation & purification , Streptomyces griseus/metabolism
19.
Adv Neonatal Care ; 15(3): 220-4, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25938952

ABSTRACT

BACKGROUND: Catheter-associated Candida bloodstream infections are a common and serious problem in the neonatal intensive care unit (NICU). Several prophylactic regimens have been developed including oral administration of nonabsorbable antifungals and intravenous infusions. No reports to date have employed a topical regimen. PURPOSE: To evaluate the effectiveness of topical nystatin cream in preventing catheter-associated Candida sepsis. METHODS: A retrospective descriptive design was used to determine the incidence of Candida sepsis in extremely low-birth weight (ELBW, <1000 g at birth) infants who were treated with topical nystatin cream for Candida bloodstream infection prophylaxis between January 1, 2000, and December 31, 2010. The electronic medical records of study infants were reviewed to establish the incidence of Candida sepsis. RESULTS: A total of 464 ELBW infants were admitted to the NICU during the study period. Three infants (0.65%) developed Candida sepsis. IMPLICATIONS FOR PRACTICE: These data demonstrate that a topical nystatin cream protocol is associated with a very low rate of Candida sepsis in ELBW infants with central catheters. The use of this protocol may contribute to a decrease in the morbidity and mortality rate associated with catheter-associated Candida infections in ELBW infants. IMPLICATIONS FOR RESEARCH: Before generalizations can be made as to the safety and efficacy of this protocol as compared to enteral and parenteral prophylactic treatments and in other institutions, large multicenter randomized controlled trials are required.


Subject(s)
Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Candidiasis/prevention & control , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Nystatin/administration & dosage , Sepsis/prevention & control , Candidiasis/nursing , Catheter-Related Infections/nursing , Female , Humans , Infant, Newborn , Infant, Premature, Diseases/prevention & control , Infant, Very Low Birth Weight , Infection Control/methods , Male , Ointments/therapeutic use , Retrospective Studies
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