SciCombinator

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Concept: Fusidic acid

29

Abstract Although erythrasma is a superficial skin infection, there is no consensus on the treatment model of erythrasma. Objective: To compare the efficacy of erythromycin, single-dose clarithromycin and topical fusidic acid in the treatment of erythrasma in a double-blind, placebo-controlled, randomized trial. Methods: Hundred and fifty-one patients over 18 years of age were included in this study. Patients were randomized and divided into five groups. They received clarithromycin, erythromycin, fusidic acid cream, placebo cream or placebo tablets. Patients were evaluated by Wood’s light reflection scores and the initial score values and the values on the days of 2, 7 and 14 were compared statistically. Results: According to the mean of Wood’s light reflection scores, the efficacy of fusidic acid cream therapy was significantly higher than other therapies. When the efficacy of clarithromycin and erythromycin therapy was compared, clarithromycin therapy was significantly more effective than erythromycin therapy at 48 h. However, there was no statistical difference on the days of 7 and 14. Conclusion: Topical fusidic acid proved to be the most effective treatment; however, clarithromycin therapy may be an alternative regimen in the treatment of erythrasma because of its efficiency and better patient’s compliance.

Concepts: Statistics, Medical terms, Light, Refraction, Randomized controlled trial, Effectiveness, Efficacy, Fusidic acid

1

Our aim was to assess national prescribing trends and determine longitudinal resistance patterns for topical antimicrobials in New Zealand. We observed a dramatic increase in fusidic acid (FA) resistance, and clonal expansion of FA-resistant Staphylococcus aureus. This increase was concurrent with a significant national increase in topical FA dispensing.

Concepts: Staphylococcus aureus, Staphylococcus, New Zealand, Antimicrobial, Fusidic acid

0

Sodium fusidate (fusidic acid) is an antimicrobial agent that is used in the treatment of staphylococcal and streptococcal infections. Several case reports have noted a drug interaction between sodium fusidate and CYP3A4 metabolised statins, leading to statin toxicity. It is unclear whether sodium fusidate has the potential to cause interactions with other cytochrome P450 enzymes.

Concepts: Pharmacology, Bacteria, Metabolism, Cytochrome P450, CYP3A4, Catalase, Statins, Fusidic acid

0

Methicillin resistance among staphylococci isolated from patients in northern Egypt has escalated alarmingly in the past decade. Data about the prevalence of fusidic acid (FA) resistance in Egyptian clinical isolates are limited. This work investigates the prevalence and mechanism of FA resistance among 81 methicillin-resistant staphylococcal isolates from major hospitals of Alexandria, Egypt. Some combinations for treating infections due to resistant isolates were studied. Twenty-six isolates (32.1%) were FA resistant (minimum inhibitory concentrations [MICs] = 2-1,024 μg/ml), and fusB and fusC genes coding for FA resistance were detected in 30.77% and 34.62% of the FA-resistant strains, respectively. One highly resistant isolate, S502 (MIC = 1,024 μg/ml), possessed both genes. Plasmid curing resulted in fusB loss and MIC decrease by 16-64 folds. Conjugation caused acquisition of FA resistance among susceptible isolates. Serial passages in subinhibitory FA concentrations produced mutants with increased MIC by 4-32 folds. The combination of FA with rifampin, gentamicin, or ampicillin/sulbactam, in a subinhibitory concentration, was synergistic against the isolates, including serial passage mutants, decreasing number of survivors by an average of 2-4 logs. A relatively moderate rate of FA resistance was detected in Alexandria hospitals. Combination therapy with gentamicin, rifampin, or ampicillin/sulbactam is crucial to preserve the effectiveness of FA.

Concepts: Bacteria, Antibiotic resistance, Plasmid, Methicillin-resistant Staphylococcus aureus, Egypt, Egyptians, Egyptian Arabic, Fusidic acid

0

Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance.

Concepts: Protein, Oxygen, Gene, Bacteria, Amino acid, Molecular biology, Antibiotic resistance, Fusidic acid

0

A significant trend towards increased fusidic acid (FA) resistance among Staphylococcus aureus with increased duration of use is of concern. The aim of the present study is to investigate the dissemination of fusidic acid resistance among Staphylococcus aureus clinical isolates.

Concepts: Present, Time, Staphylococcus aureus, Staphylococcus, Coagulase, Trend estimation, Fusidic acid

0

The objective of this study was to evaluate the healing effects of a chitosan-based, film-forming gel containing tyrothricin (TYR) in various rat wound models, including burn, abrasion, incision, and excision models. After solidification, the chitosan film layer successfully covered and protected a variety of wounds. Wound size was measured at predetermined timepoints after wound induction, and the effects of the film-forming gel were compared with negative (no treatment) and positive control groups (commercially available sodium fusidate ointment and TYR gel). In burn, abrasion and excision wound models, the film-forming gel enabled significantly better healing from 1 to 6 days after wound induction, compared with the negative control. Importantly, the film-forming gel also enabled significantly better healing compared with the positive control treatments. In the incision wound model, the breaking strength of wound strips from the group treated with the film-forming gel was significantly increased compared with both the negative and positive control groups. Histological studies revealed advanced granulation tissue formation and epithelialization in wounds treated with the film-forming gel. We hypothesize that the superior healing effects of the film-forming gel are due to wound occlusion, conferred by the chitosan film. Our data suggest that this film-forming gel may be useful in treating various wounds, including burn, abrasion, incision and excision wounds.

Concepts: Controlling for a variable, Scientific control, Scientific method, Wound healing, Collagen, Wound, Granulation tissue, Fusidic acid

0

Fusidic acid is a bacteriostatic antibiotic that is effective primarily on gram-positive bacteria, such as and species. It is often topically applied to the skin, but is also given systemically as a tablet or injection. Allergic contact dermatitis, or urticaria, has been reported as a side effect of fusidic acid treatment, whereas anaphylaxis to topically administered fusidic acid has not been reported previously. A 16-year-old boy visited an outpatient clinic for further evaluation of anaphylaxis. He suffered abrasions on his arms during exercise, which were treated with a topical ointment containing sodium fusidate. Within 30 minutes, he developed urticaria and eyelid swelling, followed by a cough and respiratory difficulty. His symptoms were relieved by emergency treatment in a nearby hospital. To investigate the etiology, oral provocation with fusidate was performed. After 125 mg (½ tablet) of sodium fusidate was administered, he developed a cough and itching of the throat within 30 minutes, which was followed by chest discomfort and urticaria. Forced expiratory volume in 1 second (FEV1) dropped from 4.09 L at baseline to 3.50 L after challenge, although wheezing was not heard in his chest. After management with an inhaled bronchodilator using a nebulizer, chest discomfort was relieved and FEV1 rose to 3.86 L. The patient was directed not to use fusidate, especially on abrasions. Here we report the first case of anaphylaxis resulting from topical fusidic acid application to abrasions.

Concepts: Asthma, Respiratory physiology, Antibiotic, Topical, Contact dermatitis, Chloramphenicol, Antibiotics, Fusidic acid

0

The objectives of this analysis were to develop a population pharmacokinetic (PK) model to describe the absorption and disposition of fusidic acid after single and multiple doses and to determine the effect of food on the rate and extent of bioavailability. Plasma PK data from three Phase 1 studies (n=75; n=14 with and without food) in which healthy subjects received sodium fusidate 500-2200 mg as single or multiple oral doses q8h or q12h for up to 7 days were modeled using S-ADAPT (MC-PEM algorithm). Accumulation of fusidic acid after multiple doses was more than that predicted based on single dose data. The PK of fusidic acid were best described using a time-dependent mixed order absorption process, two disposition compartments and a turnover process to describe the auto-inhibition of clearance. Mean total clearance (%CV) was 1.28 L/h (33) and the maximum extent of auto-inhibition was 71.0% with an IC(50) of 46.3 mg/L (36). Food decreased the extent of bioavailability by 18%. As a result of the auto-inhibition of clearance, steady state can be achieved earlier with dosing regimens that contain higher doses (after 8 days for 750 mg q12h and 1 day for 1500 mg q12h on Day 1 followed by 600 mg q12h versus 3 weeks for 500 mg q12h). Given that large initial doses auto-inhibit the clearance of fusidic acid, this characteristic provides a basis for the administration of front-loaded dosing regimens of sodium fusidate which would allow for effective concentrations to be achieved early in therapy.

Concepts: Pharmacology, Effectiveness, Dose, Absorption, Pharmacokinetics, Bioavailability, Steady state, Fusidic acid