Terbinafine Research Articles

Determination of Terbinafine at a Boron-Doped Diamond (BDD) Electrode Modified with Polypyrrole and γ-Cyclodextrin by Square Wave Voltammetry (SWV)

This work involved the determination of the antifungal agent, terbinafine (TR) using a boron-doped diamond electrode (BDD) that was modified with polypyrrole in the presence of cyclodextrin. The obtained modified layer was overoxidized and was used to develop a novel, sensitive method for terbinafine. Scan rate measurements confirmed the diffusion character of the recorded currents. Terbinafine was irreversibly oxidized, producing a well-defined peak at +1.05 V (versus the saturated calomel electrode) in Britton–Robinson (B–R) buffer at pH 6.09. Square wave voltammetry was employed to study the relationship between current and terbinafine concentration in the optimized conditions. A linear range for terbinafine determination was obtained between 7.04 × 10−8 and 9.09 × 10−7 mol/L with a limit of detection of 2.11 × 10−8 mol/L and good repeatability (2.56%, n = 6 measurements, at 3.7 × 10−7 mol/L). The procedure was employed to determine terbinafine in pharmaceutical preparations. The recovery values between 97.37 and 102.16% demonstrate the accuracy of the developed protocol.

Terbinafine hydrochloride — a drug with a wide range of antifugal protection

Terbinafine hydrochloride — a drug with a wide range of antifugal protection

Azole and terbinafine susceptibility testing of Malassezia pachydermatis in Japan.

Canine Malassezia dermatitis and otitis externa are generally treated by antifungal drugs. However, multi-drug-resistant strains of Malassezia pachydermatis have been reported worldwide. Given the presence of these multi-drug-resistant strains, it is unclear which antifungal agent is the most effective for canine Malassezia dermatitis and canine otitis. In this study, we attempted to determine the most effective drug against azole-resistant M. pachydermatis. Susceptibility to azoles and terbinafine (TBF) was assessed using a modified broth microdilution method. In all tested isolates, the minimum inhibitory concentration at 90% of organisms (MIC90) were 16 to >32 μg/mL for the azoles, and 2 μg/mL for TBF. All of the strains that showed low susceptibility to both itraconazole and miconazole were also relatively susceptible to TBF.

Comparative efficacy of 1% terbinafine hydrochloride cream and 1% ciclopirox olamine cream alone and in combination for the treatment of dermatophytosis

Background: Various antifungal agents, both in oral and topical forms, have been developed for the treatment of dermatophytosis. Aims and Objectives: The aims of this study were to evaluate the efficacy of 1% terbinafine hydrochloride cream and 1% ciclopirox olamine cream alone and in combination in the treatment of dermatophytosis. Materials and Methods: A randomized and comparative study was done at the Department of Dermatology, Government Medical College and Hospital, Chandigarh. Sixty patients of clinically diagnosed tinea corporis/tinea cruris/tinea faciei, attending the outpatient department will be allocated to three therapeutic groups of 20 patients each using random tables. Group 1: Topical 1% terbinafine hydrochloride cream twice daily for 6 weeks. Group 2: Topical 1% ciclopirox olamine cream twice daily for 6 weeks. Group 3: Topical 1% terbinafine hydrochloride cream once daily in the morning and 1% ciclopirox olamine cream once daily in the evening for 6 weeks. Inclusion criteria: (i) Body Surface Area – <10%, not requiring systemic therapy. Exclusion criteria: (i) Patients with coexisting dermatophytosis, any antifungal drugs, or pregnant, and lactating women. All the patients were assessed for therapeutic results by clinical evaluation at 3 and 6 weeks of initiation of therapy. Approved by Ethics Committee. Data collected on a pre-tested structured questionnaire and analyzed by Statistical Package for the Social Sciences. Results: After 6 weeks of treatment in Group 2, there was no erythema in 1 (6.7%) patient, moderate in 2 (13.3%) patients, mild in 12 (80%) patients, and no severity in any patient. After 6 weeks of treatment in Group 1, erythema was mild in 17 (45%) patients. After 6 weeks of treatment in Group 3, erythema was moderate in 1 (5.3%) patients, mild in 15 (78.9%) patients, and three patients had no erythema. None of the patient had severe erythema. P = 0.209 and Chi-square was 5.875. Conclusion: The combination therapy with both terbinafine hydrochloride and ciclopirox olamine group showed better response with lesser relapse rate with no significant side effects.

Antifungal Efficacy of Gallic Acid Extracted From Pomegranate Peel Against Trichophyton rubrum: In Vitro Case Study

Objectives: Trichophyton rubrum is one of the main pathogens causing superficial dermatophytosis, producing symptoms such as skin itching and pain, which seriously affects the quality of life of patients. Pomegranate peel extract is rich in gallic acid (GA), which has been reported to have biological effects including antifungal activity. However, the morphological and molecular mechanisms underlying the effects of GA on T rubrum are not well understood. The objectives of this study were to determine the antifungal efficacy of GA extracted from pomegranate peel against T rubrum in vitro, and to explore the underlying molecular mechanisms. Methods: The effects of 0-, 0.5-, and 1 mg/mL GA in pomegranate peel extract on T rubrum was investigated by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Transmission electron microscopy (TEM) was used to analyze the ultrastructure of T. rubrum, and transcriptome sequencing was used to analyze the enrichment pathway of differentially expressed genes. The identification of biosynthesis-related and key genes in the pathways involved using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) technology. Terbinafine hydrochloride (TERB) as a positive control group. Results: Pomegranate peel extract has a GA content of 1.0 mg/mL. Compared with untreated group, following treatment with 1.0 mg/mL GA content is rich in pomegranate peel extract, and the microstructure of T rubrum is destroyed. TEM results show that the number of lipid droplets in T rubrum was significantly increased, mitochondrial vacuoles degenerated, the serosa were damaged, and the boundary of thallus was unclear. In addition, 1 mg/mL GA can significantly inhibit T rubrum proliferation, and its inhibition ability is better than TERB. Transcriptomics results show that GA can change the gene expression profile of T rubrum, specifically: The biosynthesis was blocked, drug resistance was weakened, the transport of ATP-binding cassette (ABC) drugs transporter was increased, and the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited. Conclusions: Pomegranate peel extract is rich in GA, which strongly inhibited the growth of T rubrum and reduced its drug resistance. This extract is a promising natural antifungal agent for clinical use.

Long-lasting otic medications may be a rare cause of neurogenic keratoconjunctivitis sicca in dogs.

To characterize the clinical course and long-term prognosis of a suspected novel cause of neurogenic keratoconjunctivitis sicca (nKCS) secondary to florfenicol, terbinafine hydrochloride, mometasone furoate (Claro and Neptra) or florfenicol, terbinafine, betamethasone acetate (Osurnia). 29 client-owned dogs. Online survey and word-of-mouth recruitment were conducted to identify dogs that developed clinical signs of nKCS after application of otitis externa medication containing terbinafine and florfenicol. A retrospective analysis of medical records of dogs meeting inclusion criteria was then conducted. Included dogs had onset of clinical signs of nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol and had documentation of low Schirmer tear test value (< 15 mm/min) of affected eyes. 29 dogs with medical records available for review met the inclusion criteria. Documented return of clinically normal tear production was identified in 24 of 29 dogs, with a median time from application of ear medication to documented return of clinically normal tear production of 86 days (range, 19 to 482 days). A corneal ulcer was diagnosed in 68% (20/29). Multivariable Cox regression analysis showed being referred to an ophthalmologist (P = .03) and having a deep ulcer (P = .02) were associated with a longer time to documentation of Schirmer tear test ≥ 15 mm/min. Dogs that developed nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol had a good prognosis for return of normal tear production within 1 year.

In vitro Azole Susceptibility Testing of Japanese Isolates of Terbinafine-Resistant Trichophyton indotineae and Trichophyton rubrum.

Multi-antifungal-resistant strains of Trichophyton indotineae and Trichophyton rubrum have been isolated in Japan. In the present study, we examined the in vitro susceptibility of terbinafine (TRBF) -resistant isolates of T. indotineae and T. rubrum to efinaconazole (EFCZ) and luliconazole (LUCZ). In all isolates, the minimum inhibitory concentrations were ≥ 32 mg/l for TRBF, < 0.03 to 16 mg/l for itraconazole, < 0.03 to 16 mg/l for ravuconazole, < 0.03 to 0.5 mg/l for LUCZ, and < 0.03 to 4 mg/l for EFCZ. Of note, T. rubrum NUBS21012 and T. indotineae NUBS 19006T showed resistance to LUCZ and/or EFCZ unlike the other isolates.

Estimation of terbinafine HCL by spectophotometric analysis with Tpooo, Nb12br and WFB

One simple and sensitive procedure (simple spectrophotometric method) for the assay of drug Terbinafine HCl in pure form and formulations. This method involves the formation of ion-association complex between TRB and the TPOOO, NB12BR and WFB. In order to establish the optimum conditions necessary for rapid and quantitative formation of coloured product with maximum stability and sensitivity, the author performed experiments by measuring the absorbance at λmax 480nm,420nm and580nm of respective series of solutions, varying one and fixing the other parameters in each case such as type, volume and concentration of acid, organic solvent used for extraction, ratio of organic phase to aqueous phase during extraction, shaking time and temperature. The variable parameters were optimized. The results were statistically validated.

Effects of Various Emulsifying Agent and Permeability Enhancer on Percutaneous Absorption of Novel Microemulsion-Based Cream

Terbinafine hydrochloride is an antifungal drug used in the treatment of fungal infections. The oral use of terbinafine hydrochloride is not recommended as it has many potential side effects and undergoes hepatic first pass metabolism. Topical route of application has a great potential as an effective and safe way to administer drug for its antifungal in effect. The concentration of surfactant and permeation enhancer significantly affects the critical parameters of cream formulation like flux, cumulative amount released at 12 hours and enhancement ratio. In vitro permeation study across rat epidermal membrane showed that menthol enhanced the transdermal absorption of drug from cream formulation. The topical cream formulation developed in this study holds the promise for the further in vivo studies. The aim of the present work under investigation is to check the effects of emulsifying agents (Cremophor RH40, Tween 60) and permeation enhancers (l-Menthol) on cream. Developing a formulation that is safe and can deliver the drug locally in an effective concentration for its effect. The development of topical antifungal drug delivery systems designed to have localized effects appears to be very advisable and beneficial over conventional routes of provides the drug administration. However, due to the relative impermeability of the stratum corneum, which principal resistance to percutaneous absorption, extensive studies are generally necessary in order to optimize both the release of the drug from the topical vehicle and skin permeation further, A topical formulation must be both physically and chemically stable, this require numerous excipients. Aesthetically pleasing, in addition to being properties, hence they play emulsifying agents and permeation enhancers have major influence on these important role.&#x0D; Keywords: Emulsifying agents, Permeation enhancers, Stratum corneum, Antifungal, Topical cream

α-Cyclodextrin-based poly(pseudo)rotaxane for antifungal drug delivery to the vaginal mucosa

This work aimed to evaluate poly(pseudo)rotaxanes (PPRs) potential for vaginal antifungal delivery. For this, PPRs containing terbinafine (TB) 2 % were obtained using two small surfactants, Kolliphor® RH40 and Gelucire® 48/16, and different α-cyclodextrin (α-CD) concentrations (5 and 10 %). PPRs were characterized by their physicochemical characteristics, irritation, and mucoadhesion capabilities. Formulations' performance was assessed in a vertical penetration model, which uses ex vivo entire porcine vagina. Conventional penetration experiments with excised vaginal tissue were performed as a control. Results showed all formulations were non-irritant according to the HET-CAM test. Furthermore, PPRs with 10 % αCD showed superior mucoadhesion (p < 0.05). Conventional horizontal penetration studies could not differentiate formulations (p > 0.05). However, PPRs with 10 % αCD presented a better performance in vertical ex vivo studies, achieving higher drug penetration into the vaginal mucosa (p < 0.05), which is probably related to the formulation's prolonged residence time. In addition, the antifungal activity of the formulations was maintained against Candida albicans and C. glabrata cultures. More importantly, the formulation's viscosity and drug delivery control had no negative impact on the antifungal activity. In conclusion, the best performance in a more realistic model evidenced the remarkable potential of PPRs for vaginal drug delivery.

Modified Screen-Printed Microchip for Potentiometric Detection of Terbinafine Drugs

The development of miniaturized microchips has widespread and growing interest in manufacturing potentiometric sensors with extremely valuable modifying response characteristics. In this context, here, we demonstrate microfabrication, electrochemical evaluation, and analytical applications of disposable thin-film potentiometric microsensors responsive to terbinafine antifungal medication. Miniaturized microchips have been realized by integration of the sensitive layer membrane modified by carbon nanotubes onto the surface of the plastic screen-printed microchip support using a new approach, which has been recently developed. The sensitive membrane comprises terbinafine HCl: ammonium heptamolybdate complex ion pair as ionophore, o-nitrophenyl octyl ether as a solvent mediator, potassium tetrakis (4-chlorophenyl) borate as an anion excluder, and polyvinyl chloride as support. The microsensor based on this plasticised sensitive membrane provides the Nernstian response and covers a wide concentration range of terbinafine of 10−8–10−2 mole·L−1. The merits offered by the elaborated terbinafine microchip over the bulk-based electrode include reasonable sensitivity (58.5 mV/concentration decade), fast response time (∼30 s.), long-term stability (4 months), integration, and automation feasibility. Furthermore, microfabricated terbinafine chips were successfully applied to the measurements of the investigated medication in some real samples with high accuracy (96.9%) and precision (&lt;3%).

086 Terbinafine-resistant dermatophytosis: an emerging global health threat

Fungal skin infections are the most common skin disease worldwide. Superficial mycoses caused by Trichophyton rubrum and T.interdigitale are one of the leading causes for patients to seek dermatological care. Terbinafine (TRB), acting through squalene epoxidase (SQLE) inhibition, is the drug of choice for curing both species. However, TRB-resistant cases are increasing. Between 2013 and 2021, we examined TRB-sensitivity in 5435 consecutive strains of T. rubrum and T. interdigitale by testing their growth capacity on Sabouraud’s medium containing TRB.

Chitosan Nanoparticles Loaded Poloxamer 407 Gel for Transungual Delivery of Terbinafine HCl.

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm2, respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis.

Rapid back flushed direct sample injection bio-analytical HPLC-UV method for therapeutic drug monitoring of terbinafine

A rapid back flushed (BF) direct sample injection (DSI) high-performance liquid chromatography (HPLC) with UV detection (BF-DSI-HPLC-UV) has been developed to determine terbinafine (TERB) in human serum. For online solid phase extraction step, an isocratic mobile phase of phosphate buffer saline (pH 7.4) at 1 mL/min and a short protein-coated ODS column (PC-ODS-column) were used for the purification and enrichment of TERB. Two different chromatographic modes of PC-ODS-column were simultaneously operated. Macromolecular proteins were extracted by size-exclusion liquid chromatography, while TERB trapping and enrichment were achieved through reversed-phase liquid chromatography. The clear fraction containing TERB was transferred from the PC-ODS-column by BF mode onto the quantification step through a high pressure switching valve. An analytical mobile phase consisting of 80% methanol and 1% triethylamine in distilled deionized water (pH) 6 at 1 mL/min was used for the final separation on an ODS analytical column. TERB was quantified and detected by UV-detector at 224 nm. The proposed method showed high correlation coefficient (>0.999) over the concentrations range 4–1600 ng/mL with recoveries ranging from 98.48 to 93.86%. Measurement of TERB concentration in serum after administration of a single dose of 250 mg oral tablet was used to evaluate the applicability of the BF-DSI-HPLC-UV for pharmacokinetic study.

Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation.

Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections.

Penentuan Terbinafine Hidroklorida dalam Kosmetik Sediaan Pemutih Secara Kromatografi Cair Kinerja Tingg

Terbinafine hydrochloride is a synthetic allylamine drug with a broad spectrum of antifungal properties. The purpose of this study was to identify terbinafine hydrochloride in whitening cosmetic products using High Performance Liquid Chromatography (HPLC). The first stage starts with dissolving cosmetic samples (A, B, C) and blanks, diluted with 25 ml of methanol. Then the solution was vortexed for 2 and centrifuged for 10 minutes at 4000 rpm. The supernatant layer formed was filtered through a 0.45 m membrane filter. Then the filtrate obtained was tested by the HPLC method. Based on the results of the system suitability test of the sample and blank, the concentration was 16𝜇𝑔/ml, the average retention time was 8.934 minutes and the average area was 2163340. The standard deviation of the relative retention time was 0.3098% and the area was 0.0721%. The follow-up factor and theoretical plate obtained automatically from the HPLC tool obtained an average follow-up factor value of 0.9515 and an average theoretical plate value of 217.7531. The results of the HPLC system suitability test and the terbinafine hydrochloride blank were identical, but the retention time was different, obtained from each different sample. All cosmetic samples contained Terbinafine hydrochloride as they did not meet the requirements. Regulation of the Minister of Health of the Republic of Indonesia Number 3 of 2021.

Elimination of Terbinafine Hydrochloride Antifungal Drug Traces from Water, Pharmaceutical Formulations and Blood Plasma using Low-Cost Bio and Synthetic Sorbents

&lt;p&gt;:&lt;strong&gt; &lt;/strong&gt;Chitosan (CS) biosorbent and polyurethane foam (PUF) synthetic sorbent have been utilized to eliminate terbinafine hydrochloride (TRB HCl) antifungal drug in its pure and pharmaceutical forms from both contaminated aqueous and biological media using a batch process. The experimental conditions for efficient removal of TRB HCl for both CS and PUF were optimized depending on various experimental parameters such as the pH of the solution, contact periods, initial TRB HCl concentration, and sorbents dosage in the solution.&lt;/p&gt;&lt;p&gt;SEM, FT-IR, and XRD characterizations were carried out to study the adsorption of a drug by both sorbents. The optimum conditions for removing TRB HCl by CS and PUF were achieved at a pH of 8.5 and a contact time of 60 min at 250 rpm, using 0.4 g for both sorbents. The measured spectrophotometric absorbance at λ&lt;sub&gt;max&lt;/sub&gt; of TRB HCl was 242 nm. In addition, the zero-point charge (pHpzc) was determined for the studied sorbents. The pHpzc of the surface of sorbents has shown that electrostatic attraction is one of the mechanisms in TRB HCl sorption. The adsorption process was modeled using the pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion kinetic models. The results indicated that the adsorption of TRB HCl on CS and PUF does follow a pseudo-first-order type of reaction kinetics. The adsorption process was modeled using Langmuir and Freundlich isotherms. The adsorption data found that the Freundlich isotherm model was more suitable for the PUF sorbent, while the Langmuir isotherm model better fit the CS biosorbent.&lt;/p&gt;&lt;p&gt;Evaluation of the experimental data using the Langmuir equation revealed that the maximum adsorption capacities of PUF and CS were 2.807 and 1.2297 mg. g&lt;sup&gt;-1&lt;/sup&gt;, respectively. The solution was also used to estimate TRB HCl in its pharmaceutical form, and the assessed recoveries were 97.25 and 98.437% for CS and PUF, respectively. The proposed procedure was validated for other complex mediums by removing TRB HCl from spiked human blood plasma.&lt;em&gt; In-silico&lt;/em&gt; aquatic toxicity forecast of TRB HCl was also carried out.&lt;/p&gt;

A Child Girl Has Severe Case of Pediatric Atopic Dermatitis: Treatment with Terbinafine Hydrochloride

Atopic dermatitis in early childhood accounts for 20% of all atopic dermatitis occurrences, with similar atopic dermatitis symptomology of red pustules or scales characteristic. The potential causation of atopic dermatitis varies, may be hereditary in some cases. Combination topical therapies are used to treat patients with a compromised skin barrier. There are few safe and regulated pharmacotherapeutic atopic dermatitis therapies for pediatric use, and current treatment satisfaction is low. Here we provide details of the successful treatment of a pediatric patient with pustular atopic dermatitis using topical application of terbinafine hydrochloride in tandem with maternal diet control on July 22, 2020 at AYA Medical Center in Sydney, Australia. After a six-month follow-up, the patient's symptoms had fully recovered. Thus, Terbinafine hydrochloride may be useful in the treatment of atopic dermatitis in children.

P030 Highly slow-release antifungal wound dressing for chronic dermatophytosis

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesThe aim of this research was to make a biocompatible and affordable nanofibrous wound dressing that is able to release terbinafine at the site of chronic superficial fungal infection over time.MethodsPolymer solution (10%) of poly (caprolactone) (PCL) was prepared in hexafluoroisopropanol (HFIP). Terbinafine hydrochloride (TFH) was added equal to 5% of PCL weight for drug-loaded samples. Electrospinning was performed with a 27-G-needle equipped syringe at a distance of 15 cm which the injection flow rate of the solution was 0.2 ml/h and a 30 kV voltage was applied. The measurements of drug release were performed with HPLC. Antifungal tests were done on three different fungal species and MTT assay was done based on ISO-10993 on 24 h L929 cells. The drug release was monitored for 144 h in a human body simulated system (incubation at 37°C, shaking by 30 rpm, and passing the drug through a wet Whatman filter into PBS).∷ΞResultsThe mean diameter of fibers was obtained at 1262 nm for PCL nanofibers without TFH and 249 nm for PCL nanofibers with TFH. The drug loading for PCL was 83.4%. Antifungal activity of PCL fibers was examined against a dermatophyte (Trichophyton mentagrophytes), a saprophyte (Aspergillus fumigatus), and a yeast (Candida albicans). The terbinafine hydrochloride-contained electrospun PCL fibers inhibited the growth of T. Mentagrophytes and A. Fumigatus but did not inhibit C. albicans growth. None of the samples showed cytotoxic effects after 24 h and 2 weeks.ConclusionsThe diameter of PCL nanofibers with TFH apparently decreased by fives times (P >.05). PCL nanofibers successfully inhibited two important fungal species while no toxicity was observed in MTT assay for its extraction of 2 weeks. They were able to release TFH slowly over time which makes them suitable for the treatment of chronic superficial fungal infections.

P477 In vitro synergy of combination therapy against antifungal-resistant Candida spp. isolated from captive bottlenose dolphins (Tursiops truncatus)

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMThe study aimed to evaluate antifungal resistance in Candida spp. isolated from captive bottlenose dolphins (Tursiops truncatus). Due to the need to find a therapy for symptomatic animals and to the presence of azole-resistant isolates, in vitro synergy of 3 antifungal combinations has been assayed.A total of seven captive bottlenose dolphins were examined. Two dolphins showed mild aspecific symptoms, one was receiving nystatin due to gastric candidiasis, and the other four animals were asymptomatic. The presence of Candida spp. was investigated in fecal, gastric fluid, and blow samples from each dolphin twice.Samples were cultured on Sabouraud Dextrose Agar and ChromAgar Candida at 30°C for 5 days. CHROMagar colonies consistent with Candida spp. were identified.Susceptibility tests were performed according to CLSI standard with amphotericin B (AB), 5-flucytosine (FC), itraconazole (IZ), fluconazole (FZ), miconazole (MCZ), posaconazole (PZ), voriconazole (VOR), caspofungin (CAS), anidulafungin (AND), and micafungin (MF). In addition, minimum inhibitory concentration (MIC) for nystatin (NYS) and terbinafine (TER) was determined.Based on the most common therapies in dolphins, assessment of the interaction between FZ and TER, VOR and TER, and VOR and NYS was carried out determining the fractional inhibitory concentration (FIC) index by checkerboard assay.Out of 42 samples analyzed, 30 were positive for Candida spp. identified as C. albicans (n=21), C. tropicalis (n=6), and C. glabrata (n=3).All the isolates showed resistance to azoles. A total of 50% of the isolates showed resistance to FC and 23.3% to AMB. No isolate showed resistance to echinocandins.MIC values ranged from 16 to 128 µg/ml for TER (arithmetic mean 107.8 µg/ml) and from 8 to 128 µg/ml (arithmetic mean 51.8 µg/ml) for NYS.The FIC index value for FLU and TER showed a synergistic effect on 71.4% and an additive effect on 28.6% of the tested isolates.For VOR and TER an additive effect on 71.4% and a synergistic effect on 28.6% of the isolates were detected.For VOR and NYS an antagonistic effect on 71.4% and an additive effect on 28.6% of the isolates were detected.According to the results, combination therapy with FLU and TER was started. Symptoms resolved completely. Candida spp. has been isolated from mucous membranes of free-living asymptomatic dolphins. However, a high load of Candida spp. may cause clinical signs.As azoles are the most used antifungals in dolphins, azole-resistance is increasing. Since the tested dolphins had no recent history of azole treatment, it could be speculated that resistance might come from the environment. Thus, further studies and screening of multidrug-resistant Candida spp. in animals and their environment are needed to better understand resistance transmission in a One Health approach.Moreover, susceptibility testing is important to select the appropriate therapy. In case of azole-resistant Candida spp., antifungals other than azoles alone or in combination should be considered.Our study demonstrates that fluconazole exhibits in vitro synergistic antifungal activity with terbinafine against azole-resistant strains of C. albicans, C. tropicalis and C. glabrata isolated from captive bottlenose dolphins.