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Jonathan H Cove - One of the best experts on this subject based on the ideXlab platform.
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short term effects of topical Fusidic Acid or mupirocin on the prevalence of Fusidic Acid resistant fusr staphylococcus aureus in atopic eczema
British Journal of Dermatology, 2003Co-Authors: J C Ravenscroft, Alison M Layton, E A Eady, M S Murtagh, P Coates, M Walker, Jonathan H CoveAbstract:Summary Background Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical Fusidic Acid is widely used in its treatment. There is concern that topical use of Fusidic Acid may be driving the selection and dissemination of Fusidic Acid-resistant (FusR) S. aureus. Objectives To test the hypothesis that treatment of atopic eczema for 2 weeks with topical Fusidic Acid/steroid combination can increase carriage of FusRS. aureus. Methods Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% Fusidic Acid plus 0·1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0·1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. Results Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for FusRS. aureus there was no significant change in the prevalence of carriage, or population density in either group compared to baseline. Over 50% of patients carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither regimen affected either the prevalence or population density of S. aureus or FusRS. aureus in the nerves. Conclusions In this small study there is no evidence to support the hypothesis that short-term treatment of atopic eczema with Fusidic Acid/steroid combination increases Fusidic Acid resistant S. aureus during a 2-week period.
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Short‐term effects of topical Fusidic Acid or mupirocin on the prevalence of Fusidic Acid resistant (FusR) Staphylococcus aureus in atopic eczema
The British journal of dermatology, 2003Co-Authors: J C Ravenscroft, Alison M Layton, E A Eady, M S Murtagh, P Coates, M Walker, Jonathan H CoveAbstract:Summary Background Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical Fusidic Acid is widely used in its treatment. There is concern that topical use of Fusidic Acid may be driving the selection and dissemination of Fusidic Acid-resistant (FusR) S. aureus. Objectives To test the hypothesis that treatment of atopic eczema for 2 weeks with topical Fusidic Acid/steroid combination can increase carriage of FusRS. aureus. Methods Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% Fusidic Acid plus 0·1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0·1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. Results Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P
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mutation frequencies for resistance to Fusidic Acid and rifampicin in staphylococcus aureus
Journal of Antimicrobial Chemotherapy, 2001Co-Authors: Alex J Oneill, Jonathan H Cove, I. ChopraAbstract:Frequencies at which mutants resistant to Fusidic Acid and/or rifampicin arose in vitro were determined in Staphylococcus aureus strains including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA) and hetero-VISA. The concentrations of Fusidic Acid (30 and 15 mg/L) and rifampicin (16 and 1 mg/L) used for selection were equal to the expected maximum and minimum serum concentrations after an oral regimen of rifampicin 900 mg od, together with Fusidic Acid 500 mg tds. Resistant mutants arose at a frequency of around 10(-8) for selections with rifampicin, but were undetectable (frequency <10(-11)) for selections with Fusidic Acid. Mutants were not recovered (frequency <10(-11)) after selections in the presence of both Fusidic Acid and rifampicin at 30/16 and 15/1 mg/L. Our results suggest that these antibiotics, when used in combination, could have a wider role in the management of staphylococcal infections.
Thomas E. Miller - One of the best experts on this subject based on the ideXlab platform.
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Disposition of Fusidic Acid during peritoneal dialysis
Nephrology, 1997Co-Authors: John Collins, Samantha Moultrie, James W. Paxton, Glenne Findon, Ian Dittmer, Thomas E. MillerAbstract:Summary: Fusidic Acid has characteristics that suggest it might be a useful agent in the management of staphylococcal peritonitis in patients undergoing peritoneal dialysis. the present investigation was undertaken to establish the relationship between serum and peritoneal dialysis effluent concentrations of Fusidic Acid and to determine whether therapeutic levels of Fusidic Acid could be achieved in the dialysate following oral administration of the agent. Concentrations of Fusidic Acid up to 80 times the MIC for staphylococci were found after repeated oral doses. the results have provided basic data needed to initiate clinical studies of the role of Fusidic Acid as an adjunctive agent in the management of staphylococcal peritonitis.
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An experimental evaluation of the pharmacokinetics of Fusidic Acid in peritoneal dialysis.
Journal of medical microbiology, 1992Co-Authors: Louise Rowe, Glenne Findon, Thomas E. MillerAbstract:Fusidic Acid, an antimicrobial agent with activity against coagulase-positive and coagulase-negative staphylococci, has considerable potential for the management of staphylococcal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Whether Fusidic Acid reaches therapeutic levels in the dialysate once therapeutic serum levels have been achieved is not known. An animal model of CAPD that reproduced essential features of the clinical procedure was used to investigate this issue. Although oral administration was the preferred route, Fusidic Acid is not absorbed from the gastrointestinal tract of laboratory rats, and a subcutaneous injection of diethanolamine fusidate was used to achieve serum levels of the agent equivalent to those achieved clinically in man. In this model, Fusidic Acid concentrations up to 28 times the MIC for staphylococci were found in the dialysate when therapeutic levels of the agent were reached in the serum. The data provide support for continued experimental and clinical evaluation of the role of Fusidic Acid in CAPD-associated peritonitis.
I. Chopra - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Global Patterns and the Genetics of Fusidic Acid Resistance
Clinical Infectious Diseases, 2011Co-Authors: David J. Farrell, Mariana Castanheira, I. ChopraAbstract:Fusidic Acid binds to elongation factor G (EF-G), preventing its release from the ribosome, thus stalling bacterial protein synthesis. In staphylococci, high-level Fusidic Acid resistance is usually caused by mutations in the gene encoding EF-G, fusA, and low-level resistance is generally caused by the horizontally transferable mechanisms fusB and fusC that have a putative protective role on EF-G. In addition, fusD is responsible for intrinsic resistance in Staphylococcus saprophyticus, and alterations in the L6 portion of rplF (fusE) have a role in Fusidic Acid resistance. Fusidic Acid has been used in Europe and Australia for decades. More recently, it has also been used in other countries and regions, but not in the United States. Worldwide Fusidic Acid resistance has been slow to develop, and the level of resistance and genetic mechanisms responsible generally reflect the time since introduction, indications for treatment, route of administration, and prescribing practices.
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Distribution of Fusidic Acid Resistance Determinants in Methicillin-Resistant Staphylococcus aureus
Antimicrobial agents and chemotherapy, 2010Co-Authors: F. Mclaws, I. Chopra, Anders Rhod Larsen, Robert Skov, Alex J. O'neillAbstract:The prevalence of resistance to Fusidic Acid in clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), has increased in the past 2 decades. However, there are limited data regarding the relative importance in this process of the different staphylococcal determinants that mediate resistance to Fusidic Acid. Furthermore, the roles played by clonal dissemination of Fusidic Acid-resistant strains versus horizontal transmission of Fusidic Acid resistance determinants have not been investigated in detail. To gain insight into both issues, we examined Fusidic Acid resistance in 1,639 MRSA isolates collected in Denmark between 2003 and 2005. Resistance to Fusidic Acid (MIC, >1 μg/ml) was exhibited by 291 (17.6%) isolates. For the majority of these isolates (∼87%), resistance was attributed to carriage of fusB or fusC, while the remainder harbored mutations in the gene (fusA) encoding the drug target (EF-G). The CC80-MRSA-IV clone carrying fusB accounted for ∼61% of the resistant isolates in this collection, while a single CC5 clone harboring fusC represented ∼12% of the resistant strains. These findings emphasize the importance of clonal dissemination of Fusidic Acid resistance within European MRSA strains. Nonetheless, the distribution of fusB and fusC across several genetic lineages, and their presence on multiple genetic elements, indicates that horizontal transmission of Fusidic Acid resistance genes has also played an important role in the increasing prevalence of Fusidic Acid resistance in MRSA.
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Genetic Basis of Resistance to Fusidic Acid in Staphylococci
Antimicrobial agents and chemotherapy, 2007Co-Authors: Alex J. O'neill, F. Mclaws, G. Kahlmeter, A. S. Henriksen, I. ChopraAbstract:Resistance to Fusidic Acid in Staphylococcus aureus often results from acquisition of the fusB determinant or from mutations in the gene (fusA) that encodes the drug target (elongation factor G). We now report further studies on the genetic basis of resistance to this antibiotic in the staphylococci. Two staphylococcal genes that encode proteins exhibiting ca. 45% identity with FusB conferred resistance to Fusidic Acid in S. aureus. One of these genes (designated fusC) was subsequently detected in all Fusidic Acid-resistant clinical strains of S. aureus tested that did not carry fusB or mutations in fusA, and in strains of S. intermedius. The other gene (designated fusD) is carried by S. saprophyticus, explaining the inherent resistance of this species to Fusidic Acid. Fusidic Acid-resistant strains of S. lugdunensis harbored fusB. Thus, resistance to Fusidic Acid in clinical isolates of S. aureus and other staphylococcal species frequently results from expression of FusB-type proteins.
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molecular basis of fusb mediated resistance to Fusidic Acid in staphylococcus aureus
Molecular Microbiology, 2006Co-Authors: Alex J Oneill, I. ChopraAbstract:The primary mechanism of Fusidic Acid resistance in clinical strains of Staphylococcus aureus involves acquisition of the fusB determinant. The genetic elements(s) responsible are incompletely defined, and the mechanism of resistance is unknown. Here we report the cloning, sequencing and overexpression of a single gene (fusB) from plasmid pUB101 capable of conferring resistance to Fusidic Acid in S. aureus. The fusB gene is located on a transposon-like element and encodes a small (25 kDa), cytoplasmic protein for which homologues exist in a number of clinically important and environmental Gram-positive bacterial species. Bioinformatic analysis of regions immediately upstream of fusB suggested that expression of resistance is regulated by translational attenuation, which was confirmed through use of reporter fusions. FusB was overexpressed in Escherichia coli as a polyhistidine-tagged fusion product, and the purified protein shown to protect an in vitro staphylococcal translation system from inhibition by Fusidic Acid in a specific and dose-dependent fashion. Purified FusB bound staphylococcal EF-G, the target of Fusidic Acid. The protein provided no protection from inhibition by Fusidic Acid when added to an in vitro E. coli translation system, consistent both with the observed failure of FusB to bind E. coli EF-G, and its inability to confer resistance in E. coli.
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Antimicrobial activity and mechanisms of resistance to cephalosporin P1, an antibiotic related to Fusidic Acid
The Journal of antimicrobial chemotherapy, 2002Co-Authors: Alex J. O'neill, Julieanne M. Bostock, A Morais Moita, I. ChopraAbstract:The antimicrobial properties of cephalosporin P1, an antibiotic structurally related to Fusidic Acid, were examined. Cephalosporin P1 exhibited potent activity against methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus and vancomycin-intermediate S. aureus. Mutants of S. aureus resistant to cephalosporin P1 arose with a frequency of 1.6 x 10(-6) for selections at 4 x MIC, a frequency similar to that for Fusidic Acid. The mutations conferred cross-resistance to Fusidic Acid and mapped in fusA, the gene encoding elongation factor G. Cross-resistance between cephalosporin P1 and Fusidic Acid also occurred for S. aureus fusA mutants selected with Fusidic Acid, and in Fusidic Acid-resistant clinical isolates. Plasmid pUB101, which mediates resistance to Fusidic Acid in S. aureus, also conferred resistance to cephalosporin P1. Escherichia coli was intrinsically resistant to both Fusidic Acid and cephalosporin P1, but deletion of the AcrAB efflux pump resulted in susceptibility to both antibiotics. Although complete cross-resistance between Fusidic Acid and cephalosporin P1 was demonstrated, the nature and location of fusA mutations in S. aureus when cephalosporin P1 was the selective agent frequently differed from those selected with Fusidic Acid. This may reflect differences in the interaction of the two antibiotics with the translational apparatus, which results in the selection of separate mutation classes for each antibiotic. Furthermore, in three of 14 mutants selected with Fusidic Acid, resistance was attributed to mutations lying outside fusA. In contrast, mutations in 10 mutants selected with cephalosporin P1 were all located in fusA.
J C Ravenscroft - One of the best experts on this subject based on the ideXlab platform.
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short term effects of topical Fusidic Acid or mupirocin on the prevalence of Fusidic Acid resistant fusr staphylococcus aureus in atopic eczema
British Journal of Dermatology, 2003Co-Authors: J C Ravenscroft, Alison M Layton, E A Eady, M S Murtagh, P Coates, M Walker, Jonathan H CoveAbstract:Summary Background Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical Fusidic Acid is widely used in its treatment. There is concern that topical use of Fusidic Acid may be driving the selection and dissemination of Fusidic Acid-resistant (FusR) S. aureus. Objectives To test the hypothesis that treatment of atopic eczema for 2 weeks with topical Fusidic Acid/steroid combination can increase carriage of FusRS. aureus. Methods Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% Fusidic Acid plus 0·1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0·1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. Results Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for FusRS. aureus there was no significant change in the prevalence of carriage, or population density in either group compared to baseline. Over 50% of patients carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither regimen affected either the prevalence or population density of S. aureus or FusRS. aureus in the nerves. Conclusions In this small study there is no evidence to support the hypothesis that short-term treatment of atopic eczema with Fusidic Acid/steroid combination increases Fusidic Acid resistant S. aureus during a 2-week period.
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Short‐term effects of topical Fusidic Acid or mupirocin on the prevalence of Fusidic Acid resistant (FusR) Staphylococcus aureus in atopic eczema
The British journal of dermatology, 2003Co-Authors: J C Ravenscroft, Alison M Layton, E A Eady, M S Murtagh, P Coates, M Walker, Jonathan H CoveAbstract:Summary Background Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical Fusidic Acid is widely used in its treatment. There is concern that topical use of Fusidic Acid may be driving the selection and dissemination of Fusidic Acid-resistant (FusR) S. aureus. Objectives To test the hypothesis that treatment of atopic eczema for 2 weeks with topical Fusidic Acid/steroid combination can increase carriage of FusRS. aureus. Methods Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% Fusidic Acid plus 0·1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0·1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. Results Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P
Denis Spelman - One of the best experts on this subject based on the ideXlab platform.
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Fusidic Acid in skin and soft tissue infections.
International Journal of Antimicrobial Agents, 1999Co-Authors: Denis SpelmanAbstract:Skin and soft skin tissue infections are usually caused by Staphylococcus aureus and Streptococcus pyogenes. In vitro data show good activity of Fusidic Acid against staphylococci but the minimal inhibitory concentrations for streptococci are relatively high indicating marginal activity. A limited number of clinical trials have been performed using oral Fusidic Acid and although all have methodological problems the difference in susceptibility of these two organisms is apparent. The end of study cure rates for these studies were 91-99% for S. aureus and 75-85% for S. pyogenes. Topical therapy has been used in a number of forms and for different skin infections. Comparative studies have been conducted with mupirocin, trimethoprim/polymixin cream, hydrogen peroxide and combination steroid preparations. For most of these studies Fusidic Acid was equivalent to the comparator agent except where there was a proven S. pyogenes infection. Studies with topical Fusidic Acid have also been reported in specific disease states such as acne, erythrasma, and abscesses with good results.
