The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Keith T. Holland - One of the best experts on this subject based on the ideXlab platform.
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the effects of acne treatment with a combination of benzoyl peroxide and Erythromycin on skin carriage of Erythromycin resistant propionibacteria
British Journal of Dermatology, 1996Co-Authors: E.a. Eady, R.a. Bojar, C.e. Jones, Keith T. Holland, J H Cove, W.j. CunliffeAbstract:Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing Erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of Erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of Erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has greater in vivo antipropionibacterial activity than 3% w/w Erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of Erythromycin-resistant propionibacterial strains pretreatment.
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Inhibition of Erythromycin‐resistant propionibacteria on the skin of acne patients by topical Erythromycin with and without zinc
British Journal of Dermatology, 1994Co-Authors: R.a. Bojar, E.a. Eady, C.e. Jones, W.j. Cunliffe, Keith T. HollandAbstract:Summary Propionibacteria resistant to high concentrations of Erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v Erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of Erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, Erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the Erythromycin/zinc complex and Erythromycin alone produced highly significant reductions in total propionibacteria (P 4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment (seven on the Erythromycin/zinc complex and five on Erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v Erythromycin with and without zinc eradicates Erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.
W.j. Cunliffe - One of the best experts on this subject based on the ideXlab platform.
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the effects of acne treatment with a combination of benzoyl peroxide and Erythromycin on skin carriage of Erythromycin resistant propionibacteria
British Journal of Dermatology, 1996Co-Authors: E.a. Eady, R.a. Bojar, C.e. Jones, Keith T. Holland, J H Cove, W.j. CunliffeAbstract:Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing Erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of Erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of Erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has greater in vivo antipropionibacterial activity than 3% w/w Erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of Erythromycin-resistant propionibacterial strains pretreatment.
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Inhibition of Erythromycin‐resistant propionibacteria on the skin of acne patients by topical Erythromycin with and without zinc
British Journal of Dermatology, 1994Co-Authors: R.a. Bojar, E.a. Eady, C.e. Jones, W.j. Cunliffe, Keith T. HollandAbstract:Summary Propionibacteria resistant to high concentrations of Erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v Erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of Erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, Erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the Erythromycin/zinc complex and Erythromycin alone produced highly significant reductions in total propionibacteria (P 4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment (seven on the Erythromycin/zinc complex and five on Erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v Erythromycin with and without zinc eradicates Erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.
Jill Barber - One of the best experts on this subject based on the ideXlab platform.
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Erythromycin B: conformational analysis and antibacterial activity
MedChemComm, 2011Co-Authors: Paul Tyson, Abdolreza Hassanzadeh, Mohd Nizam Mordi, David G. Allison, Viter Márquez, Jill BarberAbstract:Erythromycin B, an acid-stable co-metabolite of the important antibiotic Erythromycin A, differs from Erythromycin A only in the absence of a hydroxyl group at C12, yet it has never been licensed for clinical use. We describe an NMR-based analysis of the conformation of Erythromycin B, both free in aqueous solution and when weakly bound to bacterial ribosomes and show that it is conformationally similar to Erythromycin A. The antibacterial activity of Erythromycin B is shown to be similar to that of Erythromycin A, but after acid-treatment, resembling exposure to the stomach, Erythromycin B substantially retains antibacterial activity, whereas Erythromycin A does not.
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Mechanism for the Degradation of Erythromycin A and Erythromycin A 2‘-Ethyl Succinate in Acidic Aqueous Solution
Journal of Physical Chemistry A, 2007Co-Authors: Abdolreza Hassanzadeh, Jill Barber, Gareth A. Morris, Peter A. GorryAbstract:A major drawback of the antibiotic Erythromycin A is its extreme acid sensitivity, leading to rapid inactivation in the stomach. The accepted model for degradation in aqueous acidic solution has Erythromycin A in equilibrium with Erythromycin A enol ether and degrading to anhydroErythromycin A. We report a detailed kinetic study of the acidic degradation of Erythromycin A and of Erythromycin A 2‘-ethyl succinate (the market-leading pediatric prodrug), investigating the reaction rates and degradation products via NMR. This reveals that the accepted mechanism is incorrect and that both the enol ether and the anhydride are in equilibrium with the parent Erythromycin. By implication, both the anhydride and enol ether are antibacterially inactive reservoirs for the parent Erythromycin. The actual degradation pathway is the slow loss of cladinose from Erythromycin A (or Erythromycin A 2‘-ethyl succinate), which is reported here for the first time in a kinetic study. The kinetic analysis is based on global, nonl...
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Mechanism for the Degradation of Erythromycin A and Erythromycin A 2‘-Ethyl Succinate in Acidic Aqueous Solution
The journal of physical chemistry. A, 2007Co-Authors: Abdolreza Hassanzadeh, Jill Barber, Gareth A. Morris, Peter A. GorryAbstract:A major drawback of the antibiotic Erythromycin A is its extreme acid sensitivity, leading to rapid inactivation in the stomach. The accepted model for degradation in aqueous acidic solution has Erythromycin A in equilibrium with Erythromycin A enol ether and degrading to anhydroErythromycin A. We report a detailed kinetic study of the acidic degradation of Erythromycin A and of Erythromycin A 2'-ethyl succinate (the market-leading pediatric prodrug), investigating the reaction rates and degradation products via NMR. This reveals that the accepted mechanism is incorrect and that both the enol ether and the anhydride are in equilibrium with the parent Erythromycin. By implication, both the anhydride and enol ether are antibacterially inactive reservoirs for the parent Erythromycin. The actual degradation pathway is the slow loss of cladinose from Erythromycin A (or Erythromycin A 2'-ethyl succinate), which is reported here for the first time in a kinetic study. The kinetic analysis is based on global, nonlinear, simultaneous least-squares fitting of time course concentrations for all species across multiple datasets to integrated rate expressions, to provide robust estimates of the rate constants.
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Pediatric Erythromycins: a comparison of the properties of Erythromycins A and B 2'-ethyl succinates.
Journal of Medicinal Chemistry, 2006Co-Authors: Abdolreza Hassanzadeh, Peter A. Gorry, Gareth A. Morris, Jill BarberAbstract:The antibiotic Erythromycin A is generally administered to children as a suspension of the pro-drug Erythromycin A 2‘-ethyl succinate. The success of the pro-drug depends on (a) elimination of the unacceptably bitter taste of free Erythromycin, (b) its stability against stomach acid, and (c) its smooth (base-catalyzed) hydrolysis in the body to yield active Erythromycin. We have investigated the rates and pathways of acid-catalyzed degradation and base-catalyzed hydrolysis of the 2‘-ethyl succinates of Erythromycins A and B. Esterification does not protect the drugs against acid-catalyzed degradation in solution; however, Erythromycin B 2‘-ethyl succinate is much more stable than the corresponding Erythromycin A ester, degrading nearly 40 times more slowly. The rates of base-catalyzed hydrolysis in conditions mimicking the blood stream are similar for the two pro-drugs. We conclude that Erythromycin B 2‘-ethyl succinate is an attractive prospect as a pediatric Erythromycin pro-drug.
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Design, synthesis, and evaluation of stable and taste-free Erythromycin proprodrugs.
Journal of medicinal chemistry, 2005Co-Authors: Pranab K Bhadra, Gareth A. Morris, Jill BarberAbstract:Erythromycin A is normally formulated for children as its 2'-ethyl succinate, a taste-free prodrug. Unfortunately, the prodrug hydrolyzes at a measurable rate in the medicine bottle, leading to the vile-tasting Erythromycin. We have prepared derivatives of Erythromycin B as putative paediatric prodrugs, taking advantage of the much improved acid stability of Erythromycin B relative to Erythromycin A. Thus, Erythromycin B enol ether ethyl succinate is very poorly soluble in water, and its hydrolysis is undetectable in conditions resembling the medicine bottle. In acid, however, it converts rapidly to Erythromycin B 2'-ethyl succinate, and this is in turn hydrolyzed to Erythromycin B in neutral and basic conditions. Derivatives of Erythromycin B enol ether are therefore proposed as taste-free proprodrugs of Erythromycin B.
R.a. Bojar - One of the best experts on this subject based on the ideXlab platform.
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the effects of acne treatment with a combination of benzoyl peroxide and Erythromycin on skin carriage of Erythromycin resistant propionibacteria
British Journal of Dermatology, 1996Co-Authors: E.a. Eady, R.a. Bojar, C.e. Jones, Keith T. Holland, J H Cove, W.j. CunliffeAbstract:Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing Erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of Erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of Erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has greater in vivo antipropionibacterial activity than 3% w/w Erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of Erythromycin-resistant propionibacterial strains pretreatment.
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Inhibition of Erythromycin‐resistant propionibacteria on the skin of acne patients by topical Erythromycin with and without zinc
British Journal of Dermatology, 1994Co-Authors: R.a. Bojar, E.a. Eady, C.e. Jones, W.j. Cunliffe, Keith T. HollandAbstract:Summary Propionibacteria resistant to high concentrations of Erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v Erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of Erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, Erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the Erythromycin/zinc complex and Erythromycin alone produced highly significant reductions in total propionibacteria (P 4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment (seven on the Erythromycin/zinc complex and five on Erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v Erythromycin with and without zinc eradicates Erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.
E.a. Eady - One of the best experts on this subject based on the ideXlab platform.
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the effects of acne treatment with a combination of benzoyl peroxide and Erythromycin on skin carriage of Erythromycin resistant propionibacteria
British Journal of Dermatology, 1996Co-Authors: E.a. Eady, R.a. Bojar, C.e. Jones, Keith T. Holland, J H Cove, W.j. CunliffeAbstract:Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing Erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of Erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of Erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w Erythromycin has greater in vivo antipropionibacterial activity than 3% w/w Erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of Erythromycin-resistant propionibacterial strains pretreatment.
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Inhibition of Erythromycin‐resistant propionibacteria on the skin of acne patients by topical Erythromycin with and without zinc
British Journal of Dermatology, 1994Co-Authors: R.a. Bojar, E.a. Eady, C.e. Jones, W.j. Cunliffe, Keith T. HollandAbstract:Summary Propionibacteria resistant to high concentrations of Erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v Erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of Erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, Erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the Erythromycin/zinc complex and Erythromycin alone produced highly significant reductions in total propionibacteria (P 4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F 103 c.f.u. Erythromycin-resistant propionibacteria/cm2 skin pretreatment (seven on the Erythromycin/zinc complex and five on Erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v Erythromycin with and without zinc eradicates Erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.