Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 785
Filtrar
1.
Int J Nanomedicine ; 17: 1463-1478, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35378880

RESUMO

Purpose: Fusarium Solani is the principal pathogen associated with fungal keratitis. As a sensitive drug to F. Solani, natamycin (NAT) was limited by the poor penetration and low bioavailability in clinical application. The aim of this study was to develop a new type of tri-block polymer nanoparticle-gel complex (Gel@PLGA-PEI-PEG@NAT) for delivering NAT and evaluate its physicochemical properties, antifungal activity, safety, penetrability, adhesion, and efficacy in treating fungal keratitis. Methods: PLGA-PEI-PEG@NAT was prepared and characterized with a nano-particle size analyzer, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The minimum inhibitory concentration (MIC), cytotoxicity, penetrability of NAT (Natacyn® 5% ophthalmic suspension; Alcon) and PLGA-PEI-PEG@NAT with different concentrations were assessed. The eye surface retention time, ocular irritation, and curative effect of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on a rabbit fungal keratitis model were evaluated. Results: PLGA-PEI-PEG@NAT had a particle size of 150 nm, a positive surface charge, and a sustained-release effect. The MIC for F. Solani was 2 µg/mL. A cytotoxicity test and ocular irritation test showed that PLGA-PEI-PEG@NAT and Gel@PLGA-PEI-PEG@NAT had good biocompatibility and no obvious irritation for rabbit corneas. Penetration experiments confirmed that PLGA-PEI-PEG@NAT can successfully enter corneal epithelial cells and through the cornea to enter the anterior chamber. Compared with NAT ophthalmic suspension, Gel@PLGA-PEI-PEG@NAT had stronger cornea permeation at the same concentration. The therapeutic effect and precorneal retention ability of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on the fungal keratitis rabbit model were compared. Gel@PLGA-PEI-PEG@NAT achieved a better therapeutic effect at a lower drug concentration, and its eye surface retention time was significantly longer than that of the NAT ophthalmic suspension. Conclusion: Gel@PLGA-PEI-PEG@NAT was shown to be a safe and effective nanodrug delivery system for NAT. It has great potential to improve the cure rate of fungal keratitis, reduce the administration frequency during the treatment process, and improve patient compliance.


Assuntos
Nanopartículas , Natamicina , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fusarium , Hidrogéis , Nanopartículas/química , Natamicina/farmacologia , Natamicina/uso terapêutico , Polietilenoglicóis/química , Polímeros/química , Coelhos
2.
Int J Food Microbiol ; 368: 109605, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35255244

RESUMO

Citrus sour rot caused by Geotrichum citri-aurantii is one of the most important postharvest diseases in citrus fruit, causing huge economic losses. Traditionally, it has been controlled by the postharvest application of guazatine and propiconazole fungicides, but restrictions in their use make it urgent to find an alternative for sour rot management. Natamycin, a common food preservative, and the organosulfuric compounds extracted from Allium species are safe food additives that control different foodborne pathogens. In the present study, the curative activities of commercial formulations of natamycin (Fruitgard Nat 20) and an Allium extract (PTSO: propyl thiosulfinate oxide; Proallium FRD®), were evaluated for the control of G. citri-aurantii in artificially inoculated lemon fruit. Trials in laboratory and in commercial conditions were carried out to explore the feasibility of including both compounds as part of a safe postharvest sour rot disease control strategy. Under controlled laboratory conditions, sour rot was significatively reduced by 500 mg L-1 of natamycin, 580 mL L-1 of PTSO and 290 mL L-1 of PTSO + 4% of a food coat, applied by immersion. Nevertheless, the maximum dose of PTSO (580 mL L-1) caused phytotoxicity on the fruit rind. In commercial drenching conditions, 290 mL L-1 of PTSO + 4% of a food coat reduced sour rot incidence similar to conventional treatment. In a packing line treatment, spray application of 500 mg L-1 of natamycin with a previous dip in sodium bicarbonate, resulted in nearly 70% reduction of disease incidence compared to conventional salt application. A second commercial experiment revealed that fruit drenching with 290 mL L-1 of PTSO + 4% food coat followed by an in-line cascade application of 500 mg L-1 of natamycin is completely effective for sour rot control after 20 days at 5 °C. Further exposure at room temperature for 7 d showed a 61% reduction in sour rot incidence compared to the control. Results revealed that natamycin and PTSO are promising tools for sour rot control used alone or combined as part of an integrated postharvest strategy.


Assuntos
Allium , Citrus , Frutas , Natamicina/farmacologia , Doenças das Plantas , Extratos Vegetais/farmacologia
3.
Anal Chem ; 94(8): 3553-3564, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35179030

RESUMO

Discrimination of isomers is an important and valuable feature in many analytical applications, and the identification of chiral isomers and cis-trans isomers is the current research focus. In this work, a simple method for direct, simultaneous recognition of d-/l-proline (P), d-/l-/cis-/trans-4-hydroxyproline (4-HP), and d-/l-/cis-/trans-N-tert-butoxycarbony (N-Boc-4-HP) was investigated by means of trapped ion mobility spectrometry-mass spectrometry (TIMS-MS). The isomers with cis-/trans-/d-/l-configuration can be directly recognized based on their mobility upon reaction with natamycin (Nat) and metal ions through noncovalent interactions. The results indicate that the recognition of the enantiomers has certain specificity, and the structural difference of the enantiomers was increased in a complex with Nat and metal ions. Herein, d-/l-P can be recognized through the ternary complexes [P + Nat + Mg - H]+, [P + 2Nat + Ca - H]+, [P + 2Nat + Mn - H]+, and [P + Nat + Cu - H]+. Similarly, c-4-HPL, c-4-HPD, t-4-HPL, and t-4-HPD can be recognized by [4-HP + Nat + Ca - H]+, [4-HP + 2Nat + Ca - H]+, and [4-HP + Nat + Cu - H]+, while N-Boc-c-4-HPL, N-Boc-c-4-HPD, N-Boc-t-4-HPL, and N-Boc-t-4-HPD were recognized through the enantiomer complexes [N-Boc-4-HP + Nat + Li]+, [N-Boc-4-HP + Nat + 2Na - H]+, [N-Boc-4-HP + Nat + K]+, [N-Boc-4-HP + Nat + Mn - H]+, and [N-Boc-4-HP + Nat + Ba - H]+. Moreover, tandem mass spectrometry (MS/MS) results indicated that different collision energies were obtained for the same fragment ions, which implied that the enantiomer complexes that contributed to their mobility separation shared identical interaction mode but had different gas-phase rigid geometries. Furthermore, the relative quantification for the enantiomers was performed, and the results were supported by a satisfactory coefficient (R2 > 0.99). The developed method can provide a promising and powerful strategy for the separation of chiral proline and its d-/l-/cis-/trans derivatives, bearing the advantages of higher speed, better accuracy, high selectivity, and no need for chemical derivatization and chromatographic separation.


Assuntos
Prolina , Espectrometria de Massas em Tandem , Espectrometria de Mobilidade Iônica , Íons , Natamicina , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos
4.
JAMA Ophthalmol ; 140(2): 179-184, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35024776

RESUMO

IMPORTANCE: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE: To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). CONCLUSIONS AND RELEVANCE: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Fusarium , Ceratite , Micoses , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Feminino , Humanos , Índia/epidemiologia , Ceratite/tratamento farmacológico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/microbiologia , Natamicina/farmacologia , Natamicina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Voriconazol/farmacologia , Voriconazol/uso terapêutico
5.
Bull Exp Biol Med ; 172(3): 318-323, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35001301

RESUMO

We studied whether menthol can promote penetration of natamycin, a representative antifungal macrolide agent, through the cornea. Natamycin penetration was examined using an in vitro iontophoresis system that simulates clinical scenario; menthol (0.1-0.3%, w/v) was added to the donor reservoir of a standard Franz diffusion chambers. In vivo effects of menthol on natamycin penetration were examined in a set of bioassays using rabbits inoculated with Aspergillus fumigatus in the right eye. Potential irritation to the rabbit eye was examined using a standard test. Menthol significantly (p<0.05) potentiated the effects of iontophoresis on natamycin penetration. The optimal combination seemed to be 0.2% menthol in combination with 3 mA/cm2 iontophoresis.


Assuntos
Ceratite , Natamicina , Animais , Córnea , Iontoforese , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Mentol/farmacologia , Natamicina/farmacologia , Coelhos
6.
J Mycol Med ; 32(1): 101205, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34598109

RESUMO

Tropicoporus tropicalis is an environmental basidiomycete that has been implicated in nine cases of cutaneous (n = 7) and pulmonary (n = 2) human infections predominantly in chronic granulomatous disease patients. We report here the first case of keratitis caused by Tropicoporus tropicalis in a 40-year-old immunocompetent patient, who presented with sudden diminution of vision in right eye. Corneal scrapings revealed hyaline, septate hyphae in microscopy and culture showed growth of white non-sporulating mycelial growth which was confirmed as Tropicoporus tropicalis by sequencing of ITS region of 28S rDNA. The patient was initiated on topical voriconazole along with natamycin, gatifloxacin and atropine drops. However, despite treatment, corneal ulcer perforated, for which penetrating keratoplasty was performed. Thereafter, he was prescribed amphotericin B (AMB) drops sixteen times a day and ketoconazole 200 mg twice a day with no recurrence reported over one year of follow up. The case represents the first case of infection by this fungus from India and also is the first case to be reported in an immunocompetent host.


Assuntos
Basidiomycota , Infecções Oculares Fúngicas , Ceratite , Adulto , Antifúngicos/uso terapêutico , Basidiomycota/genética , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Masculino , Natamicina
8.
Ocul Surf ; 24: 22-30, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34915188

RESUMO

Infectious keratitis is a significant cause of corneal blindness worldwide. Although less prevalent in the developed world, cases of fungal keratitis account for almost half of all keratitis cases, occurring in the developing countries. These cases are one of the most refractory types of infectious keratitis and present various challenges to the treating physician such as delayed presentation, long waiting time for culture positivity, limited availability effective antifungal drugs, prolonged duration for response to therapy, a highly variable spectrum of anti-fungal drug sensitivity and a high recurrence rate following keratoplasty. The advent of rapid diagnostic tools, molecular methods, in vitro anti-fungal drug sensitivity testing, alternatives to natamycin, targeted drug delivery and most importantly the results of large randomized controlled trials have significantly improved our understanding and approach towards the diagnosis and management of cases with fungal keratitis. Overall, Aspergillus and Fusarium species are the most common causes ones of fungal keratitis. History of antecedent trauma is a significant predisposing factor. Corneal scrapings for microscopic evaluation and culture preparation, is the standard of care for establishing the diagnosis of fungal keratitis. Molecular identification of cultures offers accurate identification of fungal pathogens, especially the rare species. Natamycin is an approved first-line drug. Voriconazole is the best alternative, especially for non-fusarium cases. Management involves administration of drugs usually by a combination of various routes, the treatment regimen being individualized depending upon the response to therapy. Photodynamic therapy is a newer treatment modality, being tried for non-responsive cases, before resorting to a therapeutic graft.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Fusarium , Ceratite , Úlcera da Córnea/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ceratite/tratamento farmacológico , Ceratite/terapia , Natamicina/farmacologia , Natamicina/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
9.
Ophthalmology ; 129(5): 530-541, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34896126

RESUMO

PURPOSE: To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis. DESIGN: Randomized controlled, single-masked, noninferiority clinical trial. PARTICIPANTS: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. METHODS: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621. MAIN OUTCOME MEASURES: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. RESULTS: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013). CONCLUSIONS: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Micoses , Adulto , Antifúngicos/uso terapêutico , Clorexidina/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Fungos , Humanos , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Micoses/microbiologia , Natamicina , Nepal , Resultado do Tratamento , Voriconazol
10.
Food Chem ; 366: 130606, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311233

RESUMO

A natamycin-based non-migratory antimicrobial packaging for extending shelf-life of yogurt drink (Doogh) was developed. Firstly, the surface of low-density polyethylene film (LDPE) was modified with acrylic acid at different times of UV exposure (0-10 min) to produce carboxylic functional groups. Then, natamycin was applied to the UV-treated films to bind covalently with the pendent functional groups. The maximum grafting efficiency (81.96%) was obtained for the 6 min treated film. Moreover, surface properties of films were evaluated by Attenuated Total Reflectance/Fourier Transfer Infrared Spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Antifungal activity of different treatments of natamycin grafted film was evaluated against two common spoilage yeasts of Doogh including Rhodotorula mucilaginosa and Candida parapsilosis. Results showed that 6 min treated film provides maximum anti-yeast activity and can be applied to control fungal growth in Doogh. Natamycin-grafted film postponed the yeast spoilage in Doogh and prolonged its shelf-life to 23 days.


Assuntos
Anti-Infecciosos , Natamicina , Anti-Infecciosos/farmacologia , Embalagem de Alimentos , Rhodotorula , Iogurte
12.
Indian J Ophthalmol ; 69(10): 2670-2674, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34571612

RESUMO

PURPOSE: To evaluate the outcomes of water-soluble intrastromal natamycin (IS-NTM) as an adjunct therapy for recalcitrant fungal keratitis. METHODS: This was a prospective interventional pilot study in the setting of a tertiary eye-care center. Twenty eyes of 20 consecutive patients with microbiologically proven recalcitrant fungal keratitis (ulcer size >2 mm, depth >50%, and not responding to topical NTM for 2 weeks) were recruited. The selected patients were injected with a novel composition of IS-NTM (10 ug/0.1 mL, soluble natamycin) prepared aseptically in the ocular pharmacology department. All the patients continued using topical NTM suspension 5% 4-hourly until the ulcer healed. Repeat injections were undertaken after 72 h depending on the clinical response and all the patients were followed till 6 months. RESULTS: The mean age of the patients was 40.42 ± 10.09 years. The mean duration of the presentation was 20.8 ± 5.1 days. The most commonly isolated organisms were Aspergillus sp. (12/20, 60%) and Fusarium sp. (8/20, 40%). No patient had iatrogenic perforation or precipitate formation after IS-NTM injection. The overall cure rate with IS-NTM was 95% (19/20 patients). The number of patients who healed with the 1st, 2nd, and 3rd injection was 13, 5, and 1, respectively. One (5%) had no response to treatment and was subjected to penetrating keratoplasty. The average time taken for the resolution of the epithelial defect, stromal infiltrates, and hypopyon was 34 ± 5.2 days, 35.3 ± 6.4 days, and 15 ± 2.5 days. Healing with deep vascularization and cataract was noted in 6/19 eyes (31%) and 13/19 eyes (68.42%), respectively. CONCLUSION: Intrastromal injection of a novel formulation of NTM holds a promising role as adjunctive therapy to topical NTM in the management of recalcitrant filamentous fungal keratitis. The preliminary results are encouraging and further studies are required to validate the results.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Adulto , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Pessoa de Meia-Idade , Natamicina , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Voriconazol
13.
Drug Deliv ; 28(1): 1836-1848, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34515597

RESUMO

Natamycin (NT) is a synthetic broad-spectrum antifungal used in eye drops. However, it has low solubility and high molecular weight, limiting its permeation, and generally causes eye discomfort or irritation when administered. Therefore, the present study aimed to develop an ophthalmic in situ gel formulation with NT-loaded cubosomes to enhance ocular permeation, improve antifungal activity, and prolong the retention time within the eye. The NT-loaded cubosome (NT-Cub) formula was first optimized using an I-optimal design utilizing phytantriol, PolyMulse, and NT as the independent formulation factors and particle size, entrapment efficiency %, and inhibition zone as responses. Phytantriol was found to increase particle size and entrapment efficiency %. Higher levels of PolyMulse slightly increased the inhibition zone whereas a decrease in particle size and EE% was observed. Increasing the NT level initially increased the entrapment efficiency % and inhibition zone. The optimized NT-Cub formulation was converted into an in situ gel system using 1.5% Carbopol 934. The optimum formula showed a pH-sensitive increase in viscosity, favoring prolonged retention in the eye. The in vitro release of NT was found to be 71 ± 4% in simulated tear fluid. The optimum formulation enhanced the ex vivo permeation of NT by 3.3 times compared to a commercial formulation and 5.2 times compared to the NT suspension. The in vivo ocular irritation test proved that the optimum formulation is less irritating than a commercial formulation of NT. This further implies that the developed formulation produces less ocular irritation and can reduce the required frequency of administration.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Géis/química , Natamicina/farmacologia , Acrilatos/química , Administração Oftálmica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Química Farmacêutica , Portadores de Fármacos , Liberação Controlada de Fármacos , Testes de Sensibilidade Microbiana , Natamicina/administração & dosagem , Natamicina/farmacocinética , Tamanho da Partícula , Coelhos
14.
Mycopathologia ; 186(6): 893-895, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34455552

RESUMO

PURPOSE: To report a case of keratomycosis caused by a very rare pathogen, Myrothecium verrucaria. METHODS: This is a case report. A 53-year-old man complaint of left eye redness, irritation, intermittent pain after ashes entered his left eye. The patient was examined by slit lamp, anterior segment OCT and in vivo confocal microscopy. The HRT III-RCM image showed massive interlocking white thin lines in the cornea stroma. Corneal scrapings were collected for pathogen culture and PCR test. M. verrucaria was isolated and identified. RESULTS: Hourly topical natamycin (5%) and voriconazole (10 mg/ml) was given as well as intravenous fluconazole (200 mg per day). Treatment was continued with oral itraconazole, 200 mg/day, topical natamycin (5%), 4 times/day, and pranoprofen, 4 times/day. The therapy was tapered off over one and half a month. The cornea lesion healed with scar formation two months later. CONCLUSIONS: This is the first case report of M. verrucaria keratomycosis in China. We are the first to show the characteristic of M. verrucaria on cornea with In vivo confocal microscopy. A combination treatment of tropical natamycin, voriconazole and systemic fluconazole was effective in the treatment of M. verrucaria.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Hypocreales , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Natamicina , Voriconazol
15.
Mycoses ; 64(10): 1183-1196, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34228832

RESUMO

BACKGROUND: Members of genus Rhodotorula are widely distributed in nature and have been traditionally considered non-pathogenic. Last few decades have seen the yeast as an emerging pathogen. We observed increase in numbers of Rhodotorula isolates from ocular infections in last few years, thus this prospective study was planned. OBJECTIVES: To identify the species of Rhodotorula isolates from ocular infections. To know the antifungal susceptibilities and study the biofilm formation attributes of the isolates. MATERIALS AND METHODS: Rhodotorula isolates were speciated using conventional methods, Matrix Assisted Laser Desorption and Ionisation - Time of Flight (MALDI- TOF) and sequencing of ITS region of ribosomal DNA. Antifungal susceptibility testing (AFST) was done using disc diffusion and E-test. Biofilm formation was studied using XTT [2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetra-zolium-5-carboxanilide] assay. RESULTS: Twenty four isolates (92.3%) were identified as R. mucilaginosa and two as R. Minuta. AFST showed high MICs against Fluconazole, Amphotericin-B, Caspofungin, Micafungin and Flucytosine; MIC distribution from low to very high against Voriconazole, Itraconazole and Natamycin; and very low MICs against Posaconazole 57.7% of isolates were strong biofilm producers, 23.1% were moderate, and 19.2% were non producers. CONCLUSIONS: This is the first prospective study on species distribution, antifungal susceptibility and biofilm production attributes of Rhodotorula isolates from ocular infections; also first time demonstrating the utility of proteomics based MALDI-TOF in diagnosing Rhodotorula up to species level. The study has shown high MICs against the conventional azoles, Amphotericin-B and Flucytosine. However, low MICs against Posaconazole and Natamycin give a hope for their possible therapeutic use.


Assuntos
Antifúngicos , Infecções Oculares , Rhodotorula , Anfotericina B , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecções Oculares/tratamento farmacológico , Infecções Oculares/microbiologia , Flucitosina , Humanos , Testes de Sensibilidade Microbiana , Natamicina , Estudos Prospectivos , Rhodotorula/efeitos dos fármacos , Rhodotorula/genética
16.
Plant Dis ; 105(11): 3653-3656, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34085850

RESUMO

Alternaria rot caused by Alternaria alternata and A. arborescens is one of the major postharvest diseases on mandarin fruit in California. In this study, natamycin, a newly registered biofungicide, was evaluated for its potential as a postharvest treatment to control Alternaria rot on mandarin fruit. The baseline sensitivities of A. alternata and A. arborescens to natamycin were determined. Effective concentration inhibiting 50% of fungal growth (EC50) values of natamycin for 70 A. alternata isolates ranged from 0.694 to 1.275 µg/ml (mean = 0.921 µg/ml) in a conidial germination assay and from 2.001 to 3.788 µg/ml (mean = 2.797 µg/ml) for 40 A. alternata isolates in a mycelial growth assay. EC50 values of natamycin for 30 A. arborescens isolates ranged from 0.698 to 1.203 µg/ml (mean = 0.923 µg/ml) in a conidial germination assay and from 2.035 to 3.368 µg/ml (mean = 2.658 µg/ml) for 20 A. arborescens isolates in a mycelial growth assay. Control tests on detached mandarin fruit showed that natamycin at both low (460 µg/ml) and high (920 µg/ml) recommended rates significantly reduced disease incidence and severity on mandarin fruit inoculated with Alternaria isolates, regardless of species. High rate of natamycin significantly reduced disease incidence and severity compared with the nontreated control even when natamycin treatment was delayed for 6, 12, and 18 h after inoculation. Our results suggested that natamycin can be an effective postharvest fungicide for control of Alternaria rot on mandarin fruit.


Assuntos
Alternaria , Fungicidas Industriais , Frutas , Fungicidas Industriais/farmacologia , Natamicina/farmacologia
18.
Sheng Wu Gong Cheng Xue Bao ; 37(4): 1107-1119, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33973428

RESUMO

Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.


Assuntos
Natamicina , Streptomyces , Antifúngicos/farmacologia , Fungos
19.
Plant Dis ; 105(10): 2907-2913, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33822660

RESUMO

Natamycin is a new postharvest biofungicide for citrus and some other fruit crops in the United States that can be effectively used in recycling drench or flooder treatments. These applications necessitate sanitation of the fungicide solution to ensure that it remains free from contamination by bacteria that are potentially human pathogens. During in vitro experiments, heated (48°C) citric acid (1,100 or 2,200 µg/ml) amended with sodium dodecylbenzenesulfonate (SDBS) (60 or 120 µg/ml, respectively) significantly reduced the viability of a nonpathogenic strain of Escherichia coli in natamycin solutions by >5 log10 compared with the control. During laboratory studies with Penicillium digitatum-inoculated lemon fruit, 1,000 µg/ml of natamycin mixed with 1,000 µg/ml of lactic acid or citric acid and with or without SDBS (55 µg/ml) effectively and significantly reduced green mold. Natamycin mixed with lactic acid at ≥2,000 µg/ml, however, caused fruit injury, resulting in browning and rind pitting. Natamycin was incompatible with peroxyacetic acid, resulting in reduced efficacy against green mold. Sodium hypochlorite mixed with natamycin lost its toxicity to E. coli; however, the performance of natamycin was not affected. With heated (average 49°C) drench treatments on an experimental packing line, natamycin (1,000 µg/ml), fludioxonil (300 µg/ml), or azoxystrobin (300 µg/ml) mixed with citric acid (1,000 µg/ml) and SDBS (55 µg/ml) were effective against green mold without fruit injury. At a pH between 3.6 and 3.8, citric acid-SDBS significantly reduced the viability of E. coli by approximately 4 log10 in mixtures with fludioxonil or azoxystrobin, but not with natamycin. However, natamycin at 1,000 µg/ml mixed with 2,000 µg/ml of citric acid and SDBS (55 µg/ml) significantly reduced E. coli counts by >4 log10 within 4 min when the pH was maintained between 3.0 and 3.3, and the efficacy of the fungicide was retained. The use of citric acid with a surfactant can be a viable alternative sanitation method for natamycin in citrus packinghouses utilizing heated recirculating fungicide systems.


Assuntos
Citrus , Fungicidas Industriais , Escherichia coli , Frutas/química , Fungicidas Industriais/farmacologia , Natamicina
20.
Eur J Pharm Sci ; 163: 105857, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882328

RESUMO

The purpose of this study was to develop, characterize and evaluate novel water soluble formulation for its topical and intrastromal application. Natamycin complexed with cyclodextrin was characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The complexed powder was used to formulate 1% w/v aqueous natamycin formulation (Natasol 1%) for topical use. The developed formulation was subjected to stability testing at various conditions. Single and multi-dose trans-corneal permeation of Natasol 1% was evaluated in New Zealand Albino rabbits in comparison with marketed 5% natamycin suspension. Sterile unpreserved Natasol (0.01% w/v natamycin) formulation was also developed for intrastromal injection. Both formulations were evaluated for the ocular toxicity. FTIR and DSC studies revealed successful complexation of natamycin that further protected the degradation at various stability conditions. Single dose trans-corneal permeation studies revealed that Natasol 1% attained Cmax at one hr and maintain its intraocular concentration 5 and 2.5 times higher at 4th and 6th hr compared to 5% natamycin suspension. Multi-dose kinetics revealed the steady state pharmacokinetics after hourly and two hourly dosing schedules. Topical Natasol 1% and sterile unpreserved Natasol 0.01% intrastromal injection, did not show any ocular toxicity in the animals. To conclude, the newly developed topical 1% w/v natamycin formulation was found to be non-inferior to 5% natamycin topical suspension. It is expected to increase patient compliance for the treatment of fungal keratitis.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Animais , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ceratite/tratamento farmacológico , Natamicina , Coelhos , Água
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...