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At least 19 recordsLinked to original sources

Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2.25 mg, placebo 2.5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these) was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis.

Adult↗

The antifungal activity of natamycin toward molds isolated from commercially manufactured poultry feed.

The antifungal activity of natamycin, a polyene antifungal compound, was evaluated on molds isolated from commercial poultry feed. The antifungal activity was measured by determination of the minimal inhibitory concentration (MIC) for natamycin on molds growing on semisolid microbiological medium (potato dextrose agar) containing pure natamycin at concentrations ranging from 0 to 200 mg/liter. Natamycin exhibited a high degree of antifungal activity against the 191 isolates of aspergilli used in this study, with average MIC values ranging from 5.08 to 40.1 mg/liter for Aspergillus fumigatus and Aspergillus parasiticus, respectively. Natamycin was also equally effective in inhibiting the growth of nonaflatoxigenic compared with aflatoxigenic isolates of Aspergillus flavus and A. parasiticus. Natamycin was also efficacious against molds other than aspergilli, with MIC values ranging from 2.15 to 5.80 mg/liter for Paecilomyces and Rhizopus spp., respectively. Natamycin exhibited apparent sporicidal activity against spores of toxigenic strains of Fusarium moniliforme and A. parasiticus but not Penicillium rubrum. This sporicidal activity was evident only when spores were exposed to an in vitro concentration of natamycin of 25 mg/liter or higher for a period of time of at least 12 hr. The growth inhibiting activity of natamycin was more pronounced compared with the sporicidal activity.

Animal Feed↗

Stability of natamycin and its cyclodextrin inclusion complexes in aqueous solution.

Aqueous solutions of natamycin and its beta-cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin, and gamma-cyclodextrin (gamma-CD) inclusion complexes were completely degraded after 24 h of exposure to 1000 lx fluorescent lighting at 4 degrees C. After 14 days of storage in darkness at 4 degrees C, 92.2% of natamycin remained in active form. The natamycin:beta-CD complex and natamycin:gamma-CD complex were significantly more stable (p < 0.05) than natamycin in its free state in aqueous solutions stored in darkness at 4 degrees C. Clear poly(ethylene terephthalate) packaging with a UV light absorber allowed 85.0% of natamycin to remain after 14 days of storage under 1000 lx fluorescent lighting at 4 degrees C. Natamycin:cyclodextrin complexes can be dissociated for analysis in methanol/water/acetic acid, 60:40:5, v/v/v. Natamycin and its complexes in dissociated form were quantified by reverse phase HPLC with detection by photodiode array at 304 nm.

Antifungal Agents↗

Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis.

PURPOSE: To determine if concurrent use of 5% natamycin and 2% econazole offers greater benefits than monotherapy with 5% natamycin for the management of fungal keratitis. METHODS: Subjects presenting to the cornea service were treated with 5% natamycin and 2% econazole used concurrently. We compared the results with a historical control of patients treated with 5% natamycin in the same calendar year. The same clinical and examination protocol including inclusion and exclusion criteria was used for both groups. RESULTS: We compared results of 47 subjects on concurrent use of 5% natamycin and 2% econazole with all 53 subjects who had received 5% natamycin in a previous study (historical controls). Baseline characteristics were similar between the 2 groups. There were no significant differences (P=0.9) between the 2 arms for success (defined as a healed or healing ulcer). CONCLUSIONS: Concurrent use of 5% natamycin and 2% econazole does not appear to offer additional benefits over monotherapy with 5% natamycin for the management of fungal keratitis.

Adult↗

Formation of natamycin:cyclodextrin inclusion complexes and their characterization.

Natamycin is a broad spectrum antimycotic with very low water solubility, which is used to extend the shelf life of shredded cheese products. beta-Cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin (HP beta-CD), and gamma-cyclodextrin (gamma-CD) were found to form inclusion complexes with natamycin in aqueous solution. The increase in solubility of natamycin with added beta-CD was observed to be linear (type A(L) phase solubility diagram). The 1:1 stability constant of natamycin:beta-CD complex was estimated from its phase solubility diagram to be 1010 M(-1). The phase solubility diagrams of both gamma-CD and HP beta-CD exhibited negative deviation from linearity (type A(N) diagram) and, therefore, did not allow the estimation of binding constants. The water solubility of natamycin was increased 16-fold, 73-fold, and 152-fold with beta-CD, gamma-CD, and HP beta-CD, respectively. The natamycin:CD inclusion complexes resulted in in vitro antifungal activity nearly equivalent to that of natamycin in its free state.

Antifungal Agents↗

[The spectrophotometric determination of natamycin in cheese].

Derivative spectroscopy was used for quantitative determination of natamycin in cheese. When measuring a methanolic cheese extract against methanol, the second derivative of the UV-spectrum is measured between 340 and 290 nm. The natamycin concentration can be determined by measuring the vertical distance between the minimum at 318 nm and the maximum at 311 nm. Under these conditions the detection limit of natamycin in a pure methanolic solution lies at 20 ng/ml, in cheese extracts at 150 ng/ml. The latter corresponds to a natamycin concentration of 2.5 ppm in the case of a 3 g test sample or 0.03 mg/dm2 in the case of a 25 cm2 cheese surface. The introduction of derivative spectroscopy makes it possible to reduce the interference of cheese substances in the photometric measurements and to increase the sensitivity and selectivity of the detection process. Besides the advantage that work and expenses are reduced - as no pimaricin-free sample has to be extracted from the interior of the cheese - it is also possible to determine natamycin photometrically in cheese, in which it is distributed homogeneously.

Cheese↗

A case-control teratological study of vaginal natamycin treatment during pregnancy.

The aim of this study was to investigate the teratogenicity of vaginal natamycin treatment during pregnancy, because the data of human epidemiological studies have not been published. Pair analysis of cases with congenital abnormalities and matched healthy controls was carried out. The population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996 included as total, 38,151 pregnant women who delivered newborn infants without any defects (control group) and 22,843 pregnant women who had fetuses or newborns with congenital abnormalities. 62 (0.27%) and 98 (0.26%) pregnant women were treated with the natamycin in the case and control groups, respectively (crude OR 1.1 with 95% CI: 0.8-1.5). A teratogenic potential of vaginal natamycin treatment during the second and third months of pregnancy, the critical period of most major congenital abnormalities, was not indicated in the case-control pair analysis (adjusted OR 0.9 with 95% CI: 0.4-1.8). A somewhat higher mean birth weight (72 g) was found in control newborn infants born to mothers with natamycin treatment compared with the data of control newborn infants without this treatment (adjusted P=0.01), though mean gestational age was shorter. The conclusion of this study is that the treatment with vaginal natamycin during pregnancy presents no detectable teratogenic risk to the fetus.

Abnormalities, Drug-Induced↗

Natamycin as a selective antifungal agent in media for growth of Legionella spp.

The growth of 18 different Legionella sp. strains and 76 different yeast isolates was tested on buffered charcoal yeast extract medium supplemented with alpha-ketoglutarate (BCYE alpha medium) and with natamycin, an antifungal agent. Bacterial growth was no different on BCYE alpha medium made with or without natamycin, whereas complete inhibition of yeasts occurred in BCYE alpha medium containing 200 to 500 micrograms of natamycin per ml. Selective BCYE alpha media made with natamycin rather than anisomycin had no (formulation with vancomycin, polymyxin B, and agar) or little (formulation with cefamandole, polymyxin B, and agar) inhibitory effect on the growth of 14 different Legionella sp. bacteria. Natamycin is an inexpensive alternative to anisomycin in the formulation of selective BCYE alpha media.

Animals↗

New high-molecular decomposition products of natamycin (pimaricin) with intact lactone-ring.

Mild acid treatment of natamycin (IV) results in biologically inactive aponatamycin (VI), an amphoteric substance with some natamycin-like chemical and physical properties. Aponatamycin contains one natamycin- and one natamycinolide-moiety. More drastic acid degradation of natamycin eliminates the aminosugar under formation of the dimer (VII) of the hypothetical aglycone of natamycin, natamycinolide (V) as well as a non-ionic compound, the dimer of the 12-decarboxy-11-anhydro analogue of natamycinolide.

Chemical Phenomena↗

Influence of inoculum type and cultivation conditions on natamycin production by Streptomyces natalensis.

This study demonstrates the effect of cultivation conditions on the production of natamycin. Of these conditions, the effect of oxygen limitation and type of inoculum were extensively investigated. Increasing the shaking speed and decreasing the medium volume improved both the volumetric and specific natamycin production. Also, decreasing the dissolved oxygen level in the cultivation medium through the addition of soluble biopolymer (alginate) resulted in a significant decrease in the natamycin yield without effect on the cell growth. On the other hand, spore inoculum yielded higher concentration of natamycin compared to the vegetative cells by about 40%. The maximal cell productivity based on biomass [Yp/x] of about 0.4 [g/g] was obtained by using shake flask of 50 ml working volume agitated at 200 rpm and the inoculum was in the form of spore 2 x 10(8) spores/ml. These results showed that the production process of natamycin is highly dependent on oxygen level in the cultivation medium and type of inoculum as well.

Culture Media↗

[Natamycin (pimaricin) in the treatment of experimental keratomycosis].

The efficacy of natamycin (pimaricin) was studied and compared with the standard amphotericin B, using a reproducible model of keratomycosis from Candida albicans in the rabbit. C. albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes. All eyes developed a corneal ulcer without pretreatment with immunosuppressive agents. Forty-eight hours after inoculation, the animals were divided into five groups: I (10 eyes) and II (12 eyes) receiving natamycin drops, 1%; groups III (12 eyes) and IV (12 eyes) receiving natamycin, 2.5%; the control group (14 eyes) receiving 0.9% NaCl. For better penetration of the drug, the epithelium of groups I and III was removed every 3rd day. Half of the control group was debrided as well. In a further series, the penetration of natamycin into the cornea and aqueous humor was studied. There was no difference between the treated eyes and the control eyes concerning complications (descemetocele or perforation). It is concluded that natamycin (pimaricin) is inferior to amphotericin B and not effective in controlling experimental keratomycosis.

Animals↗

Spectrometric and liquid chromatographic determination of natamycin in cheese and cheese rind.

Methods for determining natamycin content of cheese rind and cheese are presented. Cheese and rind samples are extracted with methanol and the fat precipitated by cooling the sample solution in methanol-water at -15 to -20 degrees C for ca 1 h. Natamycin levels are measured by UV spectrometric detection at absorbance minimum 311 nm, maximum 317 nm, and at exactly 329 nm, or by LC separation over Lichrosorb RP-8 column with detection at 303 nm. For measuring low levels, a concentration step is provided. The method is applicable to natamycin in cheese rind and in the interior of the cheese. Detection limit is 0.5 mg/kg. The method is suitable for controlling a maximum tolerance of natamycin on the cheese rind, at a level of 1 mg/dm2, and for detecting migration of natamycin into the cheese.

Cheese↗

Evaluation of a selective medium for Brucella isolation using natamycin.

AIMS: To select an anti-fungal agent to replace cycloheximide in the media used for isolation of Brucella. METHODS AND RESULTS: One potential agent, natamycin, was evaluated using 28 Brucella isolates, 18 yeasts and 14 fungi. The material for the evaluation included 37 bovine milk samples, six bovine vaginal swabs and 45 milk samples artificially infected with Brucella. The recovery of Brucella only from the artificially-inoculated milk samples increased with the use of the medium containing natamycin instead of cycloheximide, at the same time significantly inhibiting the growth of yeasts, fungi and other bacteria. The inclusion of either anti-fungal agent allowed growth of the 28 Brucella isolates and totally prevented the growth of all 18 yeasts and 13 of the 14 fungi. CONCLUSIONS: Based on the results it was concluded that natamycin would be a suitable alternative to cycloheximide. SIGNIFICANCE AND IMPACT OF THE STUDY: Cycloheximide has become unavailable worldwide and is currently an anti-fungal constituent of the medium often used for isolation of Brucella organisms. The use of natamycin as a replacement in the formulation did not inhibit growth of Brucella and was effective at eliminating most contaminants.

Animals↗

Results of a combination treatment with natamycin and butylscopolamine in cases of intestinal Candida colonization.

The findings described show that Candida species can be found in the feces of approximately half a population of nonselected test persons and in the mouths of approximately a third. Intestinal Candida colonization was found in most of these persons after one feces examination, and in practically all of them after a second examination. 10 d of therapy with 400 mg natamycin per day in sugar-coated tablet form and 40 mg natamycin in the form of tablets for sucking produced a negative fungus test for the feces in only 20% of the cases. Although a combination of this therapy with 3 x 10 mg butylscopolamine per day improved short-term results significantly, the long-term results were hardly influenced at all. Typifying results according to the Warnock method showed that we are dealing with recurrences in practically all cases and not with new infections. Minimal inhibition concentrations (MIC) of natamycin showed no marked changes as a consequence of the natamycin treatment.

Adult↗

Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh.

AIM: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis. METHODS: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial. RESULTS: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment. CONCLUSIONS: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.

Adolescent↗

Comparative study of a semisynthetic derivative of natamycin and the parent antibiotic on the spoilage of shredded cheddar cheese.

A water-soluble N-alkyl semisynthetic derivative of natamycin was synthesized by the Michael addition reaction of the parent with an N-substituted malemide. A comparative study was carried out to investigate the effectiveness of the semisynthetic derivative and the parent antibiotic in suppressing mold growth on shredded Cheddar cheese stored in modified atmosphere packaging (MAP). The effects of 0-, 10-, and 20-ppm antimycotic treatments were examined. A 20-ppm natamycin treatment effectively suppressed visible mold growth (< 10(4) CFU/g) in MAP samples for up to 30 days after packages were opened. The performance of the 20-ppm semisynthetic derivative was similar to that of the 10-ppm natamycin treatment. For these treatments, visible mold growth did not occur in MAP samples until 20 days after packages were opened. These results indicate that the semisynthetic derivative of natamycin is less effective than the parent compound in suppressing mold growth on shredded Cheddar cheese.

Antifungal Agents↗

Correlation of in vitro and in vivo susceptibility of Candida albicans to amphotericin B and natamycin.

The efficacy of topical 0.15% amphotericin B and 5% natamycin was examined in a model of Candida keratitis in rabbits and correlated with three tests of in vitro susceptibility: tube dilution minimal inhibitory concentration (MIC), minimal fungicidal concentration (MFC) and agar diffusion zones of inhibition. For a panel of 17 strains, the MIC classified precisely the same strains as resistant or susceptible to amphotericin B as did the in vivo response. Several strains were misclassified using the MFC and the zone of inhibition. For natamycin the MIC misclassified two strains but it was still superior to the other two tests. For all strains, amphotericin B was equal or superior in efficacy to natamycin in vivo. The tube dilution MIC for amphotericin B was a reliable indicator for natamycin efficacy in vivo.

Amphotericin B↗

Cytotoxicity in pig hepatocytes induced by 8-quinolinol, chloramine-T and natamycin.

The potential cytotoxic effects of the compounds 8-quinolinol, chloramine-T and natamycin have been studied in isolated pig hepatocytes. The relative cytotoxicity of these compounds was evaluated on the basis of the leakage of cytosolic lactate dehydrogenase (LDH), 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases, uptake of neutral red (NR) by cytosolic lysosomes, glutathion (GSH) depletion and oxidized glutathion (GSSG) efflux after 24 h exposure. Evaluation of the 20%, 50% and 80% reduced absorbance data obtained from the parameters NR20, NR50, and NR80, and MTT20, MTT50 and MTT80 enabled us to rank these compounds in decreasing order of cytotoxicity: 8-quinolinol > natamycin > chloramine-T. Also for the parameters LDH and GSH, chloramine-T appears to be less cytotoxic than natamycin and 8-quinolinol. Our study demonstrated that pig hepatocytes may be a useful model for examining cytotoxic events of drugs to be used in pigs, therefore avoiding possible extrapolation problems due to species differences.

Animals↗