3,313 results on '"Fusidic Acid"'
Search Results
202. Varicella-Zoster Virus Infections
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Heidelberger, A., Cremer, H., Abeck, Dietrich, editor, Burgdorf, Walter, editor, and Cremer, Hansjoerg, editor
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- 2003
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203. Antibacterial agents
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Giamarellou, H., Souli, M., Katsambas, Andreas D., editor, and Lotti, Torello M., editor
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- 2003
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204. Impetigo
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Veraldi, S., Caputo, R., Katsambas, Andreas D., editor, and Lotti, Torello M., editor
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- 2003
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205. Fever of Unknown Origin and Endocarditis
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Buscombe, J., Signore, Alberto, editor, Liberatore, Mauro, editor, and Scopinaro, Francesco, editor
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- 2003
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206. Elongation Cycle, Step III: Translocation
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Siekevitz, Philip, editor and Spirin, Alexander S.
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- 2002
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207. Non-β-Lactam Antibiotics
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Anke, T., Erkel, G., Esser, Karl, editor, Bennett, Joan W., editor, and Osiewacz, Heinz D., editor
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- 2002
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208. In vitro and in vivo antibacterial properties of peptide AMC-109 impregnated wound dressings and gels
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Joakim Håkansson, Bjarte Mortensen, John-Sigurd Svendsen, Wenche Stensen, Johan Svenson, and Jorunn Pauline Cavanagh
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Pore Forming Cytotoxic Proteins ,0301 basic medicine ,Retapamulin ,Staphylococcus aureus ,Fusidic acid ,030106 microbiology ,Antimicrobial peptides ,Pilot Projects ,Skin infection ,medicine.disease_cause ,01 natural sciences ,Microbiology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Antibiotic resistance ,In vivo ,Drug Discovery ,medicine ,Animals ,Pharmacology ,Mice, Inbred BALB C ,Wound Healing ,integumentary system ,010405 organic chemistry ,business.industry ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Antimicrobial ,Bandages ,Anti-Bacterial Agents ,0104 chemical sciences ,chemistry ,Drug Design ,Female ,Diterpenes ,business ,Fusidic Acid ,Gels ,medicine.drug - Abstract
Synthetic mimics of antimicrobial peptides (AMPs) is a promising class of molecules for a variety of antimicrobial applications. Several hurdles must be passed before effective systemic infection therapies with AMPs can be achieved, but the path to effective topical treatment of skin, nail, and soft tissue infections appears less challenging to navigate. Skin and soft tissue infection is closely coupled to the emergence of antibiotic resistance and represents a major burden to the healthcare system. The present study evaluates the promising synthetic cationic AMP mimic, AMC-109, for treatment of skin infections in vivo. The compound is evaluated both in impregnated cotton wound dressings and in a gel formulation against skin infections caused by Staphylococcus aureus and methicillin resistant S. aureus. Both the ability to prevent colonization and formation of an infection, as well as eradicate an ongoing infection in vivo with a high bacterial load, were evaluated. The present work demonstrates that AMC-109 displays a significantly higher antibacterial activity with up to a seven-log reduction in bacterial loads compared to current clinical standard therapy; Altargo cream (1% retapamulin) and Fucidin cream (2% fusidic acid) in the in vivo wound models. It is thus concluded that AMC-109 represents a promising entry in the development of new and effective remedies for various skin infections.
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- 2021
209. Fusidic acid derivatives from the endophytic fungus Acremonium pilosum F47
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Chuan Tian, Hong-Xiang Lou, Han Gao, Gang Li, and Xiao-Ping Peng
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medicine.drug_class ,Fusidic acid ,Antibiotics ,Pharmaceutical Science ,Bacillus subtilis ,medicine.disease_cause ,01 natural sciences ,Analytical Chemistry ,Microbiology ,Drug Discovery ,medicine ,Pharmacology ,biology ,010405 organic chemistry ,Acremonium ,Chemistry ,Organic Chemistry ,General Medicine ,Endophytic fungus ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Staphylococcus aureus ,Molecular Medicine ,Antibacterial activity ,Bacteria ,medicine.drug - Abstract
Fusidic acid, a representative member of fungal fusidane triterpenoids, has been clinically used as an antibiotic. In the present study, fusidic acid (1), and its known analogs 16-desacetylfusidic acid (2) and 3β,20-dihydroxy-protosta-16,24-dien-29-oic acid (4), together with one new derivative acremonidiol A (3), were isolated from the endophytic fungus, Acremonium pilosum F47. Their structures were determined by MS and NMR. The spectroscopic data of 2 are firstly reported here. The antibacterial efficacies of 1-4 were evaluated against four selected Gram-positive or Gram-negative bacteria. As expected, only compound 1 showed strong inhibitory effect on Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis.
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- 2021
210. Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo
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Lawrence A, Schachner, Anneke, Andriessen, Latanya T, Benjamin, Cristina, Claro, Lawrence F, Eichenfield, Susanna Mr, Esposito, Linda, Keller, Leon, Kircik, Pearl C, Kwong, and Catherine, McCuaig
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Staphylococcus aureus ,Evidence-Based Medicine ,Delphi Technique ,Streptococcus pyogenes ,Skin Cream ,Aminopyridines ,Microbial Sensitivity Tests ,General Medicine ,Quinolones ,Bridged Bicyclo Compounds, Heterocyclic ,Impetigo ,Anti-Bacterial Agents ,Antimicrobial Stewardship ,Mupirocin ,Drug Resistance, Bacterial ,Practice Guidelines as Topic ,Critical Pathways ,Humans ,Diterpenes ,Fusidic Acid ,Systematic Reviews as Topic - Abstract
Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations.An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics.The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported.When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.
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- 2021
211. Phenotypic and genomic characterization of Pseudomonas putida ITEM 17297 spoiler of fresh vegetables: Focus on biofilm and antibiotic resistance interaction
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Leonardo Caputo, Laura Quintieri, and Francesca Fanelli
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Lactamase ,Antibiotic resistance ,Fusidic acid ,Cold storage ,Biology ,Genome sequencing ,Applied Microbiology and Biotechnology ,Food processing and manufacture ,Microbiology ,medicine ,TX341-641 ,Biofilm eradication ,Nutrition. Foods and food supply ,Genetic transfer ,Pseudomonas ,Biofilm ,TP368-456 ,biology.organism_classification ,Pseudomonas putida ,Multiple drug resistance ,Ready-to-eat foods ,Food Science ,Biotechnology ,medicine.drug - Abstract
Pseudomonas putida is widely recognized as a spoiler of fresh foods under cold storage, and recently associated also with infections in clinical settings. The presence of antibiotic resistance genes (ARGs) could be acquired and transmitted by horizontal genetic transfer and further increase the risk associated with its persistence in food and the need to be deeper investigated. Thus, in this work we presented a genomic and phenotypic analysis of the psychrotrophic P. putida ITEM 17297 to provide new insight into AR mechanisms by this species until now widely studied only for its spoilage traits. ITEM 17297 displayed resistance to several classes of antibiotics and it also formed huge amounts of biofilm; this latter registered increases at 15 °C in comparison to the optimum growth condition (30 °C). After ITEM 17297 biofilms exposure to antibiotic concentrations higher than 10-fold their MIC values no eradication occurred; interestingly, biomasses of biofilm cultivated at 15 °C increased their amount in a dose-dependent manner. Genomic analyses revealed determinants (RND-systems, ABC-transporters, and MFS-efflux pumps) for multi-drugs resistance (β-lactams, macrolides, nalidixic acid, tetracycline, fusidic acid and bacitracin) and a novel ampC allele. Biofilm and motility related pathways were depicted underlying their contribution to AR. Based on these results, underestimated psychrotrophic pseudomonas, such as the herein studied ITEM 17297 strain, might assume relevance in relation to the risk associated with the transfer of antimicrobial resistance genes to humans through cold stored contaminated foods. P. putida biofilm and AR related molecular targets herein identified will provide a basis to clarify the interaction between AR and biofilm formation and to develop novel strategies to counteract the persistence of multidrug resistant P. putida in the food chain.
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- 2021
212. Fusidic Acid Resistance Determinants in Methicillin-Resistant Staphylococcus aureus Isolated in Kuwait Hospitals
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Wasmiyah F. Al-Musaileem, Tina Verghese, Halimah A. Boloki, Wadha Alfouzan, and Edet E. Udo
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business.industry ,Fusidic acid ,Medicine ,General Medicine ,business ,medicine.disease_cause ,Methicillin-resistant Staphylococcus aureus ,medicine.drug ,Microbiology - Abstract
Objective: The aim of this study was to investigate the genetic determinants of fusidic acid (FA) resistance in MRSA isolated from patients in Kuwait hospitals. Methods: The minimum inhibitory concentration (MIC) of FA was tested with E-test strips. Genetic determinants of FA were determined by PCR and DNA microarray. Staphylococcal protein A gene (spa) typing and DNA microarray analysis were used to study their genetic backgrounds. Results: The FA MIC ranged from 2 mg/L to >256 mg/L. Of the 97 isolates, 79 (81.4%) harbored fusC, 14 isolates harbored fusA mutations (fusA), and 4 isolates harbored fusB. Isolates with fusA mutations expressed high FA MIC (MIC >256 mg/L), whereas those with fusC and fusB expressed low FA MIC (MIC 2–16 mg/L). The isolates belonged to 23 spa types and 12 clonal complexes (CCs). The major spa types were t688 (n = 25), t311 (n = 14), t860 (n = 8), and t127 (n = 6) which constituted 54.6% of the isolates. The 12 CCs were CC1, CC5, CC8, CC15, CC22, CC80, CC88, and CC97 with CC5 (45.6%) and CC97 (13.2%) as the dominant CCs. Conclusions: The MRSA isolates belonged to diverse genetic backgrounds with the majority carrying the fusC resistance determinants. The high prevalence of FA resistance belonging to diverse genetic backgrounds warrants a review of FA usage in the country to preserve its therapeutic benefits.
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- 2021
213. A retrospective analysis of pyogenic liver abscess and antibiotic resistivity of common pathogens in Peshawar
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Muhammad Adnan Shereen, Hafiz Ullah, Muhammad Sajid, Abeer Kazmi, and Nadia Bashir
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Pyogenic liver abscess ,education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Fusidic acid ,Population ,Antibiotics ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Ciprofloxacin ,Pneumonia ,Antibiotic resistance ,Internal medicine ,Medicine ,business ,education ,Cefixime ,medicine.drug - Abstract
Background: Pyogenic liver abscess (PLA) is a rare but life-threatening disease, with a frequency ranging from 10.83 to 17.45 per 100,000 persons. The major cause of PLA is bacterial infection of liver parenchyma. The present research study was designed to investigate the common microbes causing PLA in Peshawar (Pakistan) and to evaluate a variety of the most capable and efficient antibiotics for treatment of PLA. Methods: A 7-year (2012 - 2018) retrospective demographic study of medical records of all PLA patients (n = 379) admitted to the Hayatabad Medical Complex (HMC) and Khyber Teaching Hospital (KTH) was initially performed. The demographic study was followed by biochemical tests and antibiotic resistivity tests of microorganisms, isolated from available samples and selected from literature using web services. Results & Conclusion: The demographic data revealed that 70% of the PLA patients were under the age of 50, with male predominance (male to female ratio of 3:1). It was concluded that K. pneumonia, poly-microbes (K. pneumonia and Citrobacter), and E. coli are the most common microbes involved in causing PLA in the population of Peshawar. E.coli, Citrobacter and K. pneumonia were sensitive to Cefixime and Ciprofloxacin (100% sensitivity rate), but showed significant resistance against Amoxycillin, Oxacillin and Fusidic Acid. It is, therefore, prudent to practice susceptibility-directed antibiotic therapy.
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- 2020
214. Fusidic Acid as a Potential Drug Candidate Against Infectious Gram Positive Bacteria
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Prashant Kapoor
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biology ,Chemistry ,Drug candidate ,Gram-positive bacteria ,Fusidic acid ,medicine ,General Medicine ,biology.organism_classification ,Microbiology ,medicine.drug - Published
- 2020
215. Management of acneiform rash associated with anti-EGFR monoclonal antibody treatment
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E. A. Shatokhina, L. S. Kruglova, and A. S. Polonskaia
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0301 basic medicine ,medicine.medical_specialty ,genetic structures ,Fusidic acid ,Acneiform rash ,behavioral disciplines and activities ,targeted cancer therapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Adverse effect ,Monoclonal antibody therapy ,Doxycycline ,acneiform rash ,business.industry ,General Medicine ,anti-egfr monoclonal antibodies ,supportive care ,Metronidazole ,030104 developmental biology ,dermatologic adverse events ,nervous system ,Tolerability ,030220 oncology & carcinogenesis ,Monoclonal ,Medicine ,business ,psychological phenomena and processes ,medicine.drug - Abstract
Introduction. Dermatologic adverse events (DAEs) occur in 50-90% of cases during anti-EGFR monoclonal antibody treatment. Positive correlation between the severity of acneiform rash (AR) and the effectiveness of anti-EGFR management is established. Low effectiveness of traditional treatment for AR impairs patients’ compliance, leads to dose reduction or drug discontinuation, affecting treatment results.Objective. To assess the effectiveness of traditional and proposed combined treatment for AR associated with anti-EGFR monoclonal antibody therapy.Materials and methods. 44 patients with grade I-II acneiform rash were included in a 12-week study. Patients were divided into 3 equal groups and received different treatment: group 1a – traditional therapy, group 1b – combined continuous therapy, and group 1c – combined intermittent therapy. Assessment of clinical outcomes was performed with DLQI, IGA score, and the NCI CTCAE v. 4.03.Results. The severity of AR in groups 1b and 1c improved by the end of week 1, and this trend was kept until the end of the study. The improvement was more prominent in group 1c comparing to group 1b. The severity of AR in group 1a improved by the end of week 1. During weeks 2 and 3 there was no significant change. At week 4 a deterioration of the evaluated parameters was registered, and the treatment regimen in group 1a was changed according to the treatment protocols of group 1c with rapid improvement of AR.Conclusion. Combined intermittent therapy with systemic doxycycline and topical therapy with metronidazole 1% gel and cream with hydrocortisone acetate 1% and fusidic acid 2% showed the best effectiveness and tolerability in patients with anti-EGFR monoclonal antibody-related AR.
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- 2020
216. Identifying unknown antibiotics with persistent and bioaccumulative properties and ecological risk in river water in Beijing, China
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Hongmei Cao, Weiwei Jiang, Qingshan Li, Qingwei Bu, Gang Yu, and Handan Zhang
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China ,Cefotaxime ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Fusidic acid ,Antibiotics ,010501 environmental sciences ,Biology ,Risk Assessment ,01 natural sciences ,River water ,Rivers ,Beijing ,Ampicillin ,Environmental health ,medicine ,Environmental Chemistry ,Ecological risk ,0105 earth and related environmental sciences ,Water ,General Medicine ,Pollution ,Anti-Bacterial Agents ,Bioaccumulation ,Water Pollutants, Chemical ,Environmental Monitoring ,medicine.drug - Abstract
The goal of this study was to identify antibiotics with potential risk in river water of the megacity Beijing, China. This was accomplished by using a tiered approach that combined hazard (phase I) and monitoring-based risk (phase II) assessment. Ninety-five candidate antibiotics were screened and 31 was identified as hazardous during phase I assessment. Of these hazardous antibiotics, 29 were identified as persistent and 7 were identified as bioaccumulative antibiotics. Fluoroquinolones, macrolides, sulfonamides, and aminoglycosides account for over 80% of these hazardous antibiotics. During phase II, four antibiotics (erythromycylamine, cefotaxime, ampicillin, and fusidic acid) that were not previously reported were detected in the surface water sampled from four major rivers in Beijing, with concentrations ranging from not detected to approximately 300 ng/L. The ecological risk assessment showed that erythromycylamine, cefotaxime, and ampicillin posed low to high levels of risk to the aquatic organisms. To summarize, erythromycylamine, cefotaxime, and ampicillin were identified as priority antibiotics in rivers in Beijing, China. Our results demonstrated the necessity of conducting monitoring-based verification process in identification of priority antibiotics in a specific region.
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- 2020
217. Antibiotics and the Plasmodial Plastid Organelle
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Clough, Barbara, Wilson, R. J. M., Georgiev, Vassil St., editor, and Rosenthal, Philip J., editor
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- 2001
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218. Multi-Drug-Resistant Staphylococci and Enterococci
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French, G. L., van Saene, H. K. F., editor, Sganga, G., editor, and Silvestri, L., editor
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- 2001
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219. Infections in the Neurosurgical Patient
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Korinek, Anne-Marie, Martin, Claude, Rello, Jordi, editor, Valles, Jordi, editor, and Kollef, Marin H., editor
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- 2001
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220. Novel Formulation of Fusidic Acid Incorporated into a Myrrh-Oil-Based Nanoemulgel for the Enhancement of Skin Bacterial Infection Treatment
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Wafaa Soliman, Mervat Almostafa, Heba Elsewedy, and Tamer Shehata
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Biomaterials ,Polymers and Plastics ,Organic Chemistry ,Bioengineering ,fusidic acid ,myrrh essential oil ,nanoemulgel ,optimization ,antibacterial - Abstract
Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box–Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.
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- 2022
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221. A blistering child: a toddler with large bullae
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Sophia Mohme, Matthias Goebeler, and Henning Hamm
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Male ,Blister ,Pyridines ,Child, Preschool ,Skin Cream ,Humans ,Dermatology ,Imines ,Cefaclor ,Fusidic Acid ,Impetigo ,Anti-Bacterial Agents - Published
- 2022
222. Screening of drug metabolizing enzymes for fusidic acid and its interactions with isoform-selective substrates in vitro.
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Chen, D., Lin, X.-X., Zhao, Q., Xiao, J., Peng, S.-F., Xiao, M.-F., Ouyang, D.-S., Tan, Z.-R., Wang, Y.-C., Peng, J.-B., Zhang, W., and Chen, Y.
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- *
DRUG metabolism , *OSTEOMYELITIS treatment , *CYTOCHROME P-450 , *METABOLISM , *LIVER microsomes - Abstract
1. Fusidic acid (FA) is widely used for the treatment of infections of sensitive osteomyelitis or skin and soft tissue caused by bacteria. However, the role of cytochrome P450s (CYPs) in the metabolism of FA is unclear. In the present study, we screened the main CYPs for the metabolism of FA and studied its interactions with isoform-selective substratesin vitro. 2. The main CYP450s were screened according to the inhibitory effect of specific inhibitors on the metabolism of FA in human liver microsomes (HLMs) or recombinant CYP isoforms. Enzyme kinetic parameters includingKi, Ki′, Vmax, and IC50were calculated to determine the potential of FA to affect CYP-mediated metabolism of isoform-selective substrates. 3. FA metabolism rate was inhibited by 49.8% and 83.1% under CYP2D6, CYP3A4 selective inhibitors in HLMs. In recombinant experiment, the inhibitory effects on FA metabolism were 83.3% for CYP2D6 and 58.9% for CYP3A4, respectively. FA showed inhibition on CYP2D6 and CYP3A4 withKis of 13.9 and 38.6 μM, respectively. Other CYP isoforms including CYP1A2, CYP2A6, CYP2C9, CYP2E1, and CYP2C19 showed minimal or no effect on the metabolism of FA. 4. FA was primarily metabolized by CYP2D6 and CYP3A4 and showed a noncompetitive inhibition on CYP2D6 and a mixed competitive inhibition on CYP3A4. Drug–drug interactions between FA and other chemicals, especially with substrates of CYP2D6 and CYP3A4, are phenomena that clinicians need to be aware of and cautious about. [ABSTRACT FROM PUBLISHER]
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- 2017
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223. In vitro Antimicrobial Activity of Chlorquinaldol against Microorganisms Responsible for Skin and Soft Tissue Infections: Comparative Evaluation with Gentamicin and Fusidic Acid.
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Bortolin, Monica, Bidossi, Alessandro, De Vecchi, Elena, Avveniente, Maura, and Drago, Lorenzo
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SOFT tissue infections ,ANTI-infective agents - Abstract
Skin and soft tissue infections (SSTIs) are amajor therapeutic challenge for clinicians. The emergence of pathogens with decreased susceptibility to available therapies has become an emerging problem often associated with treatment failure. Hence, there is an urgent need for novel broad-spectrum antimicrobial agents. The purpose of this study was to assess the feasibility of chlorquinaldol as an alternative approach to currently used topical antibiotics for the treatment of skin and soft tissue infections. The activity of chlorquinaldol was investigated against a collection of bacterial isolates responsible for skin infections, including strains resistant to fusidic acid and gentamicin. After determination of MIC and MBC, time-kill experiments were carried out by counting colonies grown after 0, 3, 6, 9, 24, and 48 h of incubation with concentrations equal to ¼×, ½×, 1×, 2×, and 4× MIC of chlorquinaldol, gentamicin, or fusidic acid. Staphylococci resulted the Gram-positives most sensitive to chlorquinaldol, with MIC-values ranging from 0.016 to 0.5 mg/L. A lower activity was observed against Gram-negative bacteria, with 77% of the isolates being inhibited at concentrations ranging from 128 to 512 mg/L. Generally, in time-kill studies, chlorquinaldol showed a bactericidal activity at the higher concentrations (2×, 4× MIC) after 24-48 h of incubation. In conclusion, chlorquinaldol may represent a valuable alternative to conventional topical antibiotics for the treatment of skin and soft tissue infections. [ABSTRACT FROM AUTHOR]
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- 2017
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224. Quantitative analysis of binary polymorphs mixtures of fusidic acid by diffuse reflectance FTIR spectroscopy, diffuse reflectance FT-NIR spectroscopy, Raman spectroscopy and multivariate calibration.
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Guo, Canyong, Luo, Xuefang, Zhou, Xiaohua, Shi, Beijia, Wang, Juanjuan, Zhao, Jinqi, and Zhang, Xiaoxia
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- *
QUANTITATIVE research , *FOURIER transform infrared spectroscopy , *RAMAN spectroscopy , *SUPPORT vector machines , *MIXTURES - Abstract
Vibrational spectroscopic techniques such as infrared, near-infrared and Raman spectroscopy have become popular in detecting and quantifying polymorphism of pharmaceutics since they are fast and non-destructive. This study assessed the ability of three vibrational spectroscopy combined with multivariate analysis to quantify a low-content undesired polymorph within a binary polymorphic mixture. Partial least squares (PLS) regression and support vector machine (SVM) regression were employed to build quantitative models. Fusidic acid, a steroidal antibiotic, was used as the model compound. It was found that PLS regression performed slightly better than SVM regression in all the three spectroscopic techniques. Root mean square errors of prediction (RMSEP) were ranging from 0.48% to 1.17% for diffuse reflectance FTIR spectroscopy and 1.60–1.93% for diffuse reflectance FT-NIR spectroscopy and 1.62–2.31% for Raman spectroscopy. The results indicate that diffuse reflectance FTIR spectroscopy offers significant advantages in providing accurate measurement of polymorphic content in the fusidic acid binary mixtures, while Raman spectroscopy is the least accurate technique for quantitative analysis of polymorphs. [ABSTRACT FROM AUTHOR]
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- 2017
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225. Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid.
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Marsot, Amélie, Ménard, Amelie, Dupouey, Julien, Muziotti, Cedric, Guilhaumou, Romain, and Blin, Olivier
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- *
RIFAMPIN , *PHARMACOKINETICS , *ANTITUBERCULAR agents , *JOINT infections , *INFECTIOUS arthritis , *THERAPEUTICS - Abstract
Aims Rifampicin represents the key antibiotic for the management of osteoarticular infections. An important pharmacokinetic variability has already been described, particularly for absorption and metabolism. All previous pharmacokinetic studies have been focused only on patients treated for tuberculosis. The objective of the present study was to describe a population pharmacokinetic model of rifampicin in patients with staphylococcal osteoarticular infections, which has not been investigated to date. Method Rifampicin concentrations were collected retrospectively from 62 patients treated with oral rifampicin 300 mg three times daily. Plasma concentration-time data were analysed using NONMEM to estimate population pharmacokinetic parameters. Demographic data, infection characteristics and antibiotics taken in addition to rifampicin antibiotics were investigated as covariates. Results A one-compartment model, coupled to a transit absorption model, best described the rifampicin data. Fusidic acid coadministration was identified as a covariate in rifampicin pharmacokinetic parameters. The apparent clearance and apparent central volume of distribution mean values [95% confidence interval (CI)] were 5.1 1 h-1 (1.2, 8.2 1 h-1)/23.8 l (8.9, 38.7 l) and 13.7 1 h-1 (10.6, 18.0 1 h-1)/61.1 1 (40.8, 129.0 1) for patients with and without administration of fusidic acid, respectively. Interindividual variability (95% CI) in the apparent clearance and apparent central volume of distribution were 72.9% (49.5, 86.0%) and 59.1% (5.5, 105.4%), respectively. Residual variability was 2.3 mg l-1 (1.6, 2.6 mg l-1). Conclusion We developed the first population pharmacokinetic model of rifampicin in patients with osteoarticular infections. Our model demonstrated that fusidic acid affects rifampicin pharmacokinetics, leading to potential high drug exposure. This finding suggests that fusidic acid dosing regimens should be reconsidered. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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226. Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents.
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Espinoza-Moraga, Marlene, Singh, Kawaljit, Njoroge, Mathew, Kaur, Gurminder, Okombo, John, De Kock, Carmen, Smith, Peter J., Wittlin, Sergio, and Chibale, Kelly
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AMIDE derivatives , *MULTIDRUG resistance , *CARBOXYLIC acids , *PLASMODIUM falciparum , *IN vitro studies - Abstract
A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum . Most of these derivatives showed a 4–49 and 5–17-fold increase in activity against NF54 and KI strains, respectively, as compared to FA and had a good selectivity index. These derivatives are stable over the incubation period and do not appear to be prodrugs of fusidic acid. [ABSTRACT FROM AUTHOR]
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- 2017
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227. Enterococcus faecalis OG1RF Evolution at Low pH Selects Fusidate-Sensitive Mutants in Elongation Factor G and at High pH Selects Defects in Phosphate Transport.
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Fitzgerald BA, Wadud A, Slimak Z, and Slonczewski JL
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- Humans, Anti-Bacterial Agents pharmacology, Enterococcus metabolism, Biofilms, ATP-Binding Cassette Transporters metabolism, Phosphates metabolism, Enterococcus faecalis, Peptide Elongation Factor G metabolism, Peptide Elongation Factor G pharmacology
- Abstract
Enterococcus bacteria inhabit human and soil environments that show a wide range of pH values. Strains include commensals as well as antibiotic-resistant pathogens. We investigated the adaptation to pH stress in E. faecalis OG1RF by conducting experimental evolution under acidic (pH 4.8), neutral pH (pH 7.0), and basic (pH 9.0) conditions. A serial planktonic culture was performed for 500 generations and in a high-pH biofilm culture for 4 serial bead transfers. Nearly all of the mutations led to nonsynonomous codons, indicating adaptive selection. All of the acid-adapted clones from the planktonic culture showed a mutation in fusA (encoding elongation factor G). The acid-adapted fusA mutants had a trade-off of decreased resistance to fusidic acid (fusidate). All of the base-adapted clones from the planktonic cultures as well as some from the biofilm-adapted cultures showed mutations that affected the Pst phosphate ABC transporter ( pstA , pstB , pstB2 , pstC ) and pyrR (pyrimidine biosynthesis regulator/uracil phosphoribosyltransferase). The biofilm cultures produced small-size colonies on brain heart infusion agar. These variants each contained a single mutation in pstB2 , pstC , or pyrR . The pst and pyrR mutants outgrew the ancestral strain at pH 9.2, with a trade-off of lower growth at pH 4.8. Additional genes that had a mutation in multiple clones that evolved at high pH (but not at low pH) include opp1BCDF (oligopeptide ABC transporter), ccpA (catabolite control protein A), and ftsZ (septation protein). Overall, the experimental evolution of E. faecalis showed a strong pH dependence, favoring the fusidate-sensitive elongation factor G modification at low pH and the loss of phosphate transport genes at high pH. IMPORTANCE E. faecalis bacteria are found in dental biofilms, where they experience low pH as a result of fermentative metabolism. Thus, the effect of pH on antibiotic resistance has clinical importance. The loss of fusidate resistance is notable for OG1RF strains in which fusidate resistance is assumed to be a stable genetic marker. In endodontal infections, enterococci can resist calcium hydroxide therapy that generates extremely high pH values. In other environments, such as the soil and plant rhizosphere, enterococci experience acidification that is associated with climate change. Thus, the pH modulation of natural selection in enterococci is important for human health as well as for understanding soil environments., Competing Interests: The authors declare no conflict of interest.
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- 2023
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228. Post-inflammatory hyperpigmentation after carbon dioxide laser: review of prevention and risk factors.
- Author
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Bin Dakhil A, Shadid A, and Altalhab S
- Abstract
The CO
2 laser has been widely utilized in dermatology; its expanding clinical applications include the management of neoplastic lesions, benign growths, cosmetic conditions, and reactive disorders. The laser's popularity is mainly due to the high precision and short recovery time this technology provides. However, postinflammatory hyperpigmentation (PIH) has been one of the challenging adverse effects of the CO2 laser. Therefore, several modalities have been studied for the prevention of PIH following CO2 laser treatment. This review aims to analyze the incidence of PIH after CO2 laser therapy, identify its risk factors, and assess the efficacy of the examined treatment modalities in preventing PIH. Pubmed and Embase databases were searched for this study, and relative clinical trials were included in the review. Descriptive findings - including age, gender, skin type, types of intervention, and incidence of PIH - were reported. When appropriate, the incidence of PIH was compared across each possible individual factor, such as skin type, gender, and type of intervention. A total of 211 articles were identified, and 14 relevant articles were included in this review. Seventy percent of the subjects were females (n=219), and 30% were males (n=94), with a mean age of 30 years (SD=7.8). The most common skin types were type IV (59%) followed by type III (25%). In total, eight studies investigated the prevention of PIH. The incidence of PIH after CO2 laser significantly varies between studies and differs based on the type of intervention. The studies indicate that the use of Clobetasol propionate 0.05% and fusidic acid cream appeared to effectively reduce PIH, recording an incidence rate of 39% and 53.3%, respectively. The Fitzpatrick-skinphenotype did not appear to influence the risk of PIH. There is a lack of high-powered clinical studies analyzing the incidence of PIH after CO2 laser treatment and the associated risk factors. PIH occurrence may be related to inflammation resulting from thermal damage by the CO2 laser. Consequently, the use of postoperative topical medications with anti-inflammatory properties might reduce its incidence. The use of ultra-potent topical corticosteroids and topical fusidic acid appeared to reduce PIH, possibly reducing postoperative inflammation effectively. Similarly, platelet-containing plasma may be beneficial in reducing CO2 side effects, including PIH. However, more studies are needed to further establish the influence of skin type on PIH and investigate modalities to reduce PIH occurrence after CO2 laser use., Competing Interests: Conflict of interest: the authors declare no conflict of interest., (Copyright © 2023, the Author(s).)- Published
- 2023
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229. Treatment of Clostridium difficile-Associated Diarrhea and Colitis
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Gerding, D. N., Compans, R. W., editor, Cooper, M., editor, Ito, Y., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Vogt, P. K., editor, Wagner, H., editor, Aktories, Klaus, editor, and Wilkins, Tracy D., editor
- Published
- 2000
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230. Antibacterial Agents in Dermatology
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Giamarellou, H., Katsambas, Andreas D., editor, and Lotti, Torello M., editor
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- 2000
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231. Folliculitis
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Rousselet, G. R., Katsambas, Andreas D., editor, and Lotti, Torello M., editor
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- 2000
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232. Cicatricial Alopecia
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Tosti, A., Piraccini, B. M., Katsambas, Andreas D., editor, and Lotti, Torello M., editor
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- 2000
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233. Antimicrobials
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Humbert, Philippe, Gabard, Bernard, editor, Surber, Christian, editor, Elsner, Peter, editor, and Treffel, Pierre, editor
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- 2000
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234. Topical Treatment
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Plewig, Gerd, Kligman, Albert M., Plewig, Gerd, and Kligman, Albert M.
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- 2000
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235. A Randomized Study Evaluating Oral Fusidic Acid (CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified Drug-Drug Interaction.
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Pushkin, Richard, Iglesias-Ussel, Maria D., Keedy, Kara, MacLauchlin, Chris, Mould, Diane R., Berkowitz, Richard, Kreuzer, Stephan, Darouiche, Rabih, Oldach, David, and Fernandes, Prabha
- Subjects
- *
ANTIBIOTICS , *RIFAMPIN , *REIMPLANTATION (Surgery) , *DEBRIDEMENT , *PHARMACOKINETICS - Abstract
Background. Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described. Methods. In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively. Results. Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected. Conclusions. The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research. [ABSTRACT FROM AUTHOR]
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- 2016
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236. A study on community associated Staphylococcus aureus and its susceptibility pattern to Mupirocin and Fusidic acid in primary pyoderma patients.
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Sethi, Pihu, Betkerur, Jayadev, Sethi, Parth, Adhlakha, Bhuvan, Kulkarni, Madhuri, and Murthy, Krishna C.
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- *
STAPHYLOCOCCUS aureus , *METHICILLIN-resistant staphylococcus aureus , *MUPIROCIN , *PYODERMA , *SKIN diseases - Abstract
Background: Primary pyodermas are one of the most common dermatological diseases. Staphylococcus aureus (S. aureus) is frequently isolated. It has developed resistance to many antimicrobials and Methicillin Resistant Staphylococcus aureus (MRSA) is a major problem. The precipitous usage of topical antimicrobials especially Mupirocin and Fusidic acid has increased the development of multi-resistant strains of S. aureus and in India, few studies have shown susceptibility profile to these drugs. Aim: This study aimed at the clinical and bacteriological profile in primary pyoderma patients, prevalence of MRSA and the resistance pattern of S. aureus to Mupirocin and Fusidic acid. Materials and methods: Patients with primary pyodermas from community were recruited. Gram stain and culture sensitivity was done with swabs taken from the lesions. Antibiotic susceptibility for S. aureus was tested using VITEK-2. Mupirocin and Fusidic acid susceptibility was determined by Estrip method. Observations: A total of 107 patients of primary pyodermas were included. Pyoderma were common in young age group (P = 0.001). Poor hygiene was the main predisposing factor. Furunculosis (45.8%) was the most common pyoderma followed by impetigo and folliculitis (16.8% each). Culture was positive in all except 3. S. aureus was isolated in 61.7% and polymicrobial flora in 13.1%. Prevalence of MRSA was 39.5% (P= 0.066). All strains of S. aureus demonstrated 100% susceptibility to Mupirocin and Fusidic acid. Conclusions: Furunculosis still has the highest incidence in adult population with a high prevalence of MRSA (39.5%). Despite extensive usage of Mupirocin and Fusidic acid, no resistance was found in this part of India. [ABSTRACT FROM AUTHOR]
- Published
- 2016
237. Elongation Cycle, Step III: Translocation
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Spirin, Alexander S., Siekevitz, Philip, editor, and Spirin, Alexander S.
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- 1999
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238. Cloning and Sequencing of a New Comamonas Testosteroni Gene Encoding 3α-Hydroxysteroid Dehydrogenase/Carbonyl Reductase
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Möbus, Eric, Maser, Edmund, Weiner, Henry, editor, Maser, Edmund, editor, Crabb, David W., editor, and Lindahl, Ronald, editor
- Published
- 1999
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239. Literature-Based Phenotype Survey and In Silico Genotype Investigation of Antibiotic Resistance in the Genus Bifidobacterium
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Changhui Zhao, Qinghao Wang, Yunfei Hu, Yongfei Hu, Baiyuan Li, Linyan Cao, Yeshi Yin, and Huahai Chen
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Genotype ,Tetracycline ,Fusidic acid ,In silico ,Mupirocin ,Biology ,Applied Microbiology and Biotechnology ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Plasmid ,Antibiotic resistance ,medicine ,Humans ,Computer Simulation ,030304 developmental biology ,Genetics ,0303 health sciences ,030306 microbiology ,Drug Resistance, Microbial ,General Medicine ,Anti-Bacterial Agents ,Housekeeping gene ,Phenotype ,chemistry ,Genes, Bacterial ,Bifidobacterium ,medicine.drug - Abstract
Bifidobacteria are typical commensals inhabiting the human intestine and are beneficial to the host because of their probiotic properties. One of the risks concerning probiotics is the potential of introducing antibiotic resistance genes (ARGs) to the host gut pathogens. This study was aimed to depict the general antibiotic resistance characteristics of the genus Bifidobacterium by combining the reported phenotype dataset and in silico genotype prediction. Bifidobacteria were mostly reported to be sensitive to beta-lactams, glycopeptides, chloramphenicol, and rifampicin, but resistant to aminoglycosides, polypeptides, quinolones, and mupirocin. Generally, the resistance phenotypes to erythromycin, tetracycline, fusidic acid, metronidazole, clindamycin, and trimethoprim were variable. Besides cmX and tetQ, characterized in bifidobacterial resident plasmids, 3520 putative ARGs were identified from 831 bifidobacterial genomes through BLASTP search. The identified ARGs matched thirty-eight reference ARGs, four of which seemed to be mutant housekeeping genes. The two high-abundant ARGs, tetW and ermX, were found to have different distribution traits. The predicted ARGs reasonably explained most of the corresponding resistant phenotypes in the published literature.
- Published
- 2020
240. Fusidic acid cream comparatively minimizes signs of inflammation and postinflammatory hyperpigmentation after ablative fractional CO 2 laser resurfacing in Chinese patients: A randomized controlled trial
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Min Wei, Li Li, Baoxi Wang, Yan Yan, Xiaofeng Zhang, and Mengna Li
- Subjects
medicine.medical_specialty ,business.industry ,Fusidic acid ,Erythromycin ,Inflammation ,Dermatology ,Hyperpigmentation ,Surgery ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Ablative case ,medicine ,medicine.symptom ,Adverse effect ,business ,Postinflammatory hyperpigmentation ,medicine.drug - Abstract
BACKGROUND Inflammation and postinflammatory hyperpigmentation (PIH) are two adverse side effects of ablative fractional CO2 laser (ablative Fr CO2 ) treatment for both rejuvenation and acne scars. AIMS To evaluate the efficacy of fusidic acid cream versus erythromycin ointment as postoperative therapy in patients who underwent ablative Fr CO2 treatment for atrophic acne scars. METHODS Sixty Chinese patients who fulfilled the study criteria were recruited and randomly assigned to an experimental group treated with fusidic acid cream or a control group treated with erythromycin ointment. Postoperative treatment lasted for 7 days in each group. Each patient had two follow-up visits at 8 and 12 weeks. In total, three patients dropped out of the study, one in the experimental group at week 8 and two in the control group at weeks 8 and 12. Baseline and postoperative inflammation and PIH were assessed by facial examination, photographs, and questionnaires. Besides, PIH was evaluated by the Hyperpigmentation Activity and Severity Index (HASI) and a five-point grading system. RESULTS Moderate-to-severe PIH was observed in both groups. However, the mean HASI score and severity of PIH in the experimental group were lower than those of the control group at weeks 8 and 12 (P
- Published
- 2020
241. Chitosan and phospholipid assisted topical fusidic acid drug delivery in burn wound: Strategies to conquer pharmaceutical and clinical challenges, opportunities and future panorama
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Jitender Madan, Shashi Bala Singh, Monika Chaudhary, Manish Goswami, Monika Sharma, Om Prakash Katare, Kiran Jyoti, and Garima Malik
- Subjects
medicine.medical_specialty ,Chemical Phenomena ,medicine.drug_class ,Fusidic acid ,Antibiotics ,02 engineering and technology ,Drug resistance ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,Drug Delivery Systems ,Structural Biology ,Drug Resistance, Bacterial ,medicine ,Humans ,Intensive care medicine ,Molecular Biology ,Phospholipids ,030304 developmental biology ,Chitosan ,Drug Carriers ,0303 health sciences ,Topical drug ,Burn wound ,business.industry ,General Medicine ,021001 nanoscience & nanotechnology ,Bandages ,Methicillin-resistant Staphylococcus aureus ,Low and middle income countries ,Drug delivery ,Burns ,0210 nano-technology ,business ,Fusidic Acid ,medicine.drug - Abstract
Burn is the immense public health issue globally. Low and middle income countries face extensive deaths owing to burn injuries. Availability of conventional therapies for burns has always been painful for patients as well as expensive for our health system. Pharmaceutical experts are still searching reliable, cheap, safe and effective treatment options for burn injuries. Fusidic acid is an antibiotic of choice for the management of burns. However, fusidic acid is encountering several pharmaceutical and clinical challenges like poor skin permeability and growing drug resistance against burn wound microbes like Methicillin resistant Staphylococcus aureus (MRSA). Therefore, an effort has been made to present a concise review about molecular pathway followed by fusidic acid in the treatment of burn wound infection in addition to associated pros and cons. Furthermore, we have also summarized chitosan and phospholipid based topical dermal delivery systems customized by our team for the delivery of fusidic acid in burn wound infections on case-to-case basis. However, every coin has two sides. We recommend the integration of in-silico docking techniques with natural biomacromolecules while designing stable, patient friendly and cost effective topical drug delivery systems of fusidic acid for the management of burn wound infection as future opportunities.
- Published
- 2020
242. Fusidic acid resistance through changes in the dynamics of the drug target
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Jennifer Tomlinson, Arnout P. Kalverda, and Antonio N. Calabrese
- Subjects
conformational flexibility ,Models, Molecular ,Steric effects ,antibiotic resistance ,Protein Conformation ,medicine.drug_class ,Fusidic acid ,Antibiotics ,Drug target ,Allosteric regulation ,Ribosome ,Antibiotic resistance ,Bacterial Proteins ,Protein Domains ,FusB ,Drug Resistance, Bacterial ,medicine ,Multidisciplinary ,biology ,Chemistry ,Biological Sciences ,Peptide Elongation Factor G ,biology.organism_classification ,Elongation Factor G ,NMR ,Anti-Bacterial Agents ,Biophysics and Computational Biology ,Biophysics ,sense organs ,Fusidic Acid ,Bacteria ,medicine.drug - Abstract
Significance The World Health Organization has declared antimicrobial resistance one of the greatest threats to human health. Understanding the molecular mechanisms by which bacteria resist the effects of antibiotic therapies is central to understanding antimicrobial resistance and to informing the development of new treatments that can circumvent these resistance mechanisms. This study reveals the molecular details of the mechanism of FusB-mediated resistance to fusidic acid, an important clinical treatment for Staphylococcus aureus infections, including methicillin-resistant Staphylococcus aureus. Here we elucidate an antibiotic resistance mechanism driven by an allosteric effect on the conformational flexibility of the drug target., Antibiotic resistance in clinically important bacteria can be mediated by target protection mechanisms, whereby a protein binds to the drug target and protects it from the inhibitory effects of the antibiotic. The most prevalent source of clinical resistance to the antibiotic fusidic acid (FA) is expression of the FusB family of proteins that bind to the drug target (Elongation factor G [EF-G]) and promote dissociation of EF-G from FA-stalled ribosome complexes. FusB binding causes changes in both the structure and conformational flexibility of EF-G, but which of these changes drives FA resistance was not understood. We present here detailed characterization of changes in the conformational flexibility of EF-G in response to FusB binding and show that these changes are responsible for conferring FA resistance. Binding of FusB to EF-G causes a significant change in the dynamics of domain III of EF-GC3 that leads to an increase in a minor, more disordered state of EF-G domain III. This is sufficient to overcome the steric block of transmission of conformational changes within EF-G by which FA prevents release of EF-G from the ribosome. This study has identified an antibiotic resistance mechanism mediated by allosteric effects on the dynamics of the drug target.
- Published
- 2020
243. Origin and Evolution of Fusidane-Type Antibiotics Biosynthetic Pathway through Multiple Horizontal Gene Transfers
- Author
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Huifeng Jiang, Yuqian Liu, Tao Liu, Wenjing Fan, Jian Cheng, Xiaonan Liu, Lina Lu, Shiheng Tao, Xiaoxian Guo, Xiangchen Li, and Yanhe Ma
- Subjects
Gene Transfer, Horizontal ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Cytochrome P-450 Enzyme System ,Genetics ,Intramolecular Transferases ,Gene ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,biology ,Phylogenetic tree ,Fungi ,Sordariomycetes ,biology.organism_classification ,Biological Evolution ,Anti-Bacterial Agents ,Biosynthetic Pathways ,Metabolic pathway ,Eurotiomycetes ,Multigene Family ,Horizontal gene transfer ,Genome, Fungal ,Fusidic Acid ,030217 neurology & neurosurgery ,Pezizomycotina ,Research Article - Abstract
Fusidane-type antibiotics represented by fusidic acid, helvolic acid, and cephalosporin P1 have very similar core structures, but they are produced by fungi belonging to different taxonomic groups. The origin and evolution of fusidane-type antibiotics biosynthetic gene clusters (BGCs) in different antibiotics producing strains remained an enigma. In this study, we investigated the distribution and evolution of the fusidane BGCs in 1,284 fungal genomes. We identified 12 helvolic acid BGCs, 4 fusidic acid BGCs, and 1 cephalosporin P1 BGC in Pezizomycotina fungi. Phylogenetic analyses indicated six horizontal gene transfer (HGT) events in the evolutionary trajectory of the BGCs, including 1) three transfers across Eurotiomycetes and Sordariomycetes classes; 2) one transfer between genera under Sordariomycetes class; and 3) two transfers within Aspergillus genus under Eurotiomycetes classes. Finally, we proposed that the ancestor of fusidane BGCs would be originated from the Zoopagomycota by ancient HGT events according to the phylogenetic trees of key enzymes in fusidane BGCs (OSC and P450 genes). Our results extensively clarify the evolutionary trajectory of fusidane BGCs by HGT among distantly related fungi and provide new insights into the evolutionary mechanisms of metabolic pathways in fungi.
- Published
- 2020
244. A Detailed Study of Antimicrobial Sensitivity Pattern of Penton Valentine Leucocidin Gene Positive and Negative Staphylococcus aureus from Pus Samples
- Author
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Asim Saifullah, Mateen Izhar, Mariya Ali, Asma Yaqoob, Asma Akram, and Anwaar Basheer
- Subjects
General Computer Science ,medicine.drug_class ,business.industry ,Fusidic acid ,Antibiotics ,Erythromycin ,respiratory system ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Antimicrobial ,medicine.disease_cause ,Microbiology ,Multiple drug resistance ,Ciprofloxacin ,Staphylococcus aureus ,medicine ,bacteria ,Gentamicin ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Introduction: Staphylococcus aureus harboring Panton Valentine Leucocidin gene are emerging and spreading worldwide. PVL gene was first identified by Noel Panton and Francis Valentine in 1932 who IC Pakistan only limited data is available regarding the effect of PVL gene on sensitivity pattern of Staphylococcus aureus. Therefore, this study was conducted to understand the antimicrobial sensitivity pattern of both PVL positive and negative Staphylococcus aureus isolates. Aims & Objectives: This study was conducted to understand the antimicrobial sensitivity pattern of both PVL positive and PVL negative Staphylococcus aureus isolated from pus samples received from various indoor and outdoor departments of a tertiary care hospital of Lahore. Place and duration of study: Microbiology and Molecular Biology Laboratory Shaikh Zayed Hospital Lahore. Duration of study is one year after the approval of research topic. Material & Methods: A total of 384 Staphylococcus aureus isolates from skin and soft tissue infections were identified and selected. Their antimicrobial sensitivity testing was done by Kirby disc diffusion method using Muller Hinton agar. Results: Frequencies of PVL gene in MRSA and MSSA were 51% and 44% respectively. Frequency of PVL gene was also found to be high in Ciprofloxacin sensitive, Gentamicin sensitive, Erythromycin resistant and fusidic acid resistant isolates. Conclusion: Almost half of Staphylococcus aureus isolates were found PVL positive. They were mostly multidrug resistant. The PVL positive Staphylococcus aureus isolates showed high resistance against antibiotics than PVL negative isolates
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- 2020
245. A self-assembled polymer therapeutic for simultaneously enhancing solubility and antimicrobial activity and lowering serum albumin binding of fusidic acid
- Author
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Pavan Walvekar, Chunderika Mocktar, Nikita Devnarain, Victoria Oluwaseun Fasiku, Calvin A. Omolo, Thirumala Govender, Mohammed Salih, Ahmed A. Elrashedy, and Ayman Y. Waddad
- Subjects
Methicillin-Resistant Staphylococcus aureus ,biology ,Polymers ,Chemistry ,Microscale thermophoresis ,Fusidic acid ,Serum albumin ,General Medicine ,Pharmacology ,Antimicrobial ,Human serum albumin ,medicine.disease_cause ,Molecular Docking Simulation ,Antibiotic resistance ,Solubility ,Structural Biology ,Staphylococcus aureus ,Drug delivery ,medicine ,biology.protein ,Fusidic Acid ,Molecular Biology ,Serum Albumin ,medicine.drug - Abstract
The global antimicrobial resistance crisis has prompted worldwide efforts to develop new and more efficient antimicrobial compounds, as well as to develop new drug delivery strategies and targeting mechanisms. This study aimed to synthesize a novel polyethylene glycol-fusidic acid (PEG-FA) conjugate for self-assembly into nano-sized structures and explore its potential for simultaneously enhancing aqueous solubility and antibacterial activity of FA. In addition, the ability of PEG-FA to bind to HSA with lower affinity than FA is also investigated. Haemolysis and in vitro cytotoxicity studies confirmed superior biosafety of the novel PEG-FA compared to FA. The water solubility of FA after PEG conjugation was increased by 25-fold compared to the bare drug. PEG-FA nanoparticles displayed particle size, polydispersity index and zeta potential of 149.3 ± 0.21 nm, 0.267 ± 0.01 and 5.97 ± 1.03 mV, respectively. Morphology studies using high-resolution transmission electron microscope revealed a homogenous spherical shape of the PEG-FA nanoparticles. In silico studies showed that Van der Waals forces facilitated PEG-FA self-assembly. HSA binding studies showed that PEG-FA had very weak or no interaction with HSA using in silico molecular docking (-2.93 kcal/mol) and microscale thermophoresis (Kd=14999 ± 1.36 µM), which may prevent bilirubin displacement. Conjugation with PEG did not inhibit the antibacterial activity of FA but rather enhanced it by 2.5-fold against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, compared to the bare FA. These results show that PEG-FA can simultaneously enhance solubility and antibacterial activity of FA, whilst also reducing binding of HSA to decrease its side effects. Communicated by Ramaswamy H. Sarma
- Published
- 2020
246. Current status of Panton–Valentine leukocidin‐positive methicillin‐resistant Staphylococcus aureus isolated from patients with skin and soft tissue infections in Japan
- Author
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Yasushi Matsuzaki, Naoko Baba, Shigeho Shirahama, Osamu Nemoto, Daisuke Sawamura, Norihisa Noguchi, Masami Ikeda, Nao Sasai, Satoru Kawasaki, Sakae Funatsu, Toru Ueki, Fumiko Shimoe, Yoko Kobayashi, Yoichi Inaba, Hidemasa Nakaminami, and Kazuya Ozawa
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Staphylococcus aureus ,Fusidic acid ,Bacterial Toxins ,Exotoxins ,Dermatology ,Skin infection ,medicine.disease_cause ,Microbiology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Leukocidins ,Humans ,Medicine ,skin and connective tissue diseases ,business.industry ,Soft Tissue Infections ,Outbreak ,General Medicine ,Minocycline ,Staphylococcal Infections ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Antimicrobial ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Community-Acquired Infections ,030220 oncology & carcinogenesis ,Panton–Valentine leukocidin ,business ,medicine.drug - Abstract
The USA300 clone, which produces Panton-Valentine leukocidin (PVL), is a major pathogenic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone that causes intractable skin infections. Recently, PVL-positive CA-MRSA, including USA300 clones, have emerged in both communities and hospitals in Japan. To prevent an outbreak of PVL-positive MRSA, infected patients should be treated with effective antimicrobial agents at community clinics. Herein, we investigate molecular epidemiological characteristics of PVL-positive MRSA isolated from outpatients with skin and soft tissue infections (SSTI), which are common community-onset infectious diseases. The detection rate of MRSA was 24.9% (362 strains) out of 1455 S. aureus strains isolated between 2013 and 2017. Among the MRSA strains, 15.5% (56 strains) were PVL-positive strains and associated with deep-seated skin infections. Molecular epidemiological analyses of PVL-positive MRSA showed that USA300 was the predominant clone (53.6%, 30 strains) and was identified in Kanto (18 strains), Kagawa (nine strains), Tohoku (two strains) and Hokkaido (one strain). Notably, minocycline and fusidic acid were effective against all PVL-positive MRSA strains. Hence, our data reveals the current status of PVL-positive MRSA isolated from patients with SSTI in Japan. Continuous surveillance of CA-MRSA is necessary to monitor latest prevalence rates and identify effective antimicrobial agents for PVL-positive MRSA strains.
- Published
- 2020
247. Modern approaches to treatment of superficial pyoderma
- Author
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K.I. Bezvershenko
- Subjects
medicine.medical_specialty ,Impetigo ,integumentary system ,medicine.drug_class ,business.industry ,Fusidic acid ,Antibiotics ,Bacitracin ,medicine.disease ,medicine.disease_cause ,Dermatology ,Bullous impetigo ,Staphylococcus aureus ,Cellulitis ,medicine ,skin and connective tissue diseases ,Abscess ,business ,medicine.drug - Abstract
Impetigo is the most common bacterial skin infection in children. The disease has two forms: nonbullous and bullous, of which nonbullous is the most common (70 %). Impetigo is caused by Staphylococcus aureus, Streptococcus pyogenes, or their combinations. In nonbullous impetigo, methicillinresistant strains (MRSA) of S. aureus are most often detected. For the colonization of staphylococcus and streptococcus, the necessary conditions are damage to the integrity of the skin and violation of the composition of the usual microflora of the skin. Patients with inflammatory skin diseases are most often colonized by S. aureus and are at high risk for developing MRSA infections. In bullous impetigo, the rash elements are represented by bullae which quickly burst with the formation of surface erosion and a yellow crust. Nonbullous impetigo is manifested by vesicles, pustules, crusts. Typically, impetigo is clinically diagnosed. Suspicion of MRSA occurs in cases of spontaneous abscess or cellulitis, or if lesions are not eliminated by the recommended initial treatment with antibiotics. Topical therapy is the first line of treatment for uncomplicated nonbullous and bullous impetigo. If the lesion is limited to a small area (up to 6 cm2), the treatment involves soaking the crusts, exfoliating them and applying antimicrobial ointments (fusidic acid or a combination of neomycin and bacitracin) (EBM Guidelines, 2018). With more diffuse lesions, systemic antibiotic therapy is prescribed. In treatment of patients with eczema, topical and systemic antimicrobials with topical steroids are used. The combination of the aminoglycoside antibiotic neomycin and the polypeptide antibiotic bacitracin is presented at the Ukrainian pharmaceutical market as Baneocin drug. This combination has a pronounced synergistic effect on S. aureus, S. pyogenes and P. aeryginosa. An important advantage of Baneocin is its availability in two forms (powder and ointment), which allows the use of this drug at different stages of the infection process.
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- 2020
248. Formulation and Evaluation of Fusidic Acid Emulgel
- Author
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Hitesh Jain, Ankita Srivastava, Sharav Desai, and Dhananjay Meshram
- Subjects
Chromatography ,Chemistry ,Fusidic acid ,medicine ,medicine.drug - Abstract
Emulgel have emerged as one of the most interesting topical delivery system as it has dual control release system i.e gel and emulsion. Topical applications of drug offers many advantages for delivering drug directly to the site of action and deliver the drug for extended period of time at effected site. The major objective behind this formulation is to enhance topical delivery of hydrophobic drug (Fusidic acid) by formulating Fusidic acid emulgel by using carbopol 934 as gelling agent. In addition light liquid paraffin as oil, span 20 as emulsifier and propylene glycol as co-surfactant were selected for the preparation of emulgel. Fusidic acid is steroidal bacteriostatic agent produced from Fusidium coccineum fungus belongs to class of steroids but has no corticosteroids effect and which is useful for the treatment of number of infections. Fusidic acid binds to protein and ribosomes and inhibits bacterial protein synthesis. The prepared emulgel were evaluated for their physical appearance, pH determination, viscosity, spreadability, in-vitro drug release, antimicrobial activity, skin irritation study and stability. All the prepared emulgel showed acceptable physical properties. The best formulation E9 shows better drug release when compared to all formulation. Keywords: Emulgel, Carbopol 934, Topical formulation, Antimicrobial activity, optimization, Fusidic acid
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- 2020
249. Indole Derivatives of Fusidane Triterpenoids: Synthesis and the Antibacterial Activity
- Author
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Aygul A. Magafurova, O. S. Kukovinets, Elena V. Tretyakova, E. V. Salimova, and Lyudmila V. Parfenova
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Indole test ,Strain atcc ,010405 organic chemistry ,Chemistry ,Fusidic acid ,Organic Chemistry ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,In vitro ,0104 chemical sciences ,Triterpenoid ,Staphylococcus aureus ,medicine ,Cytotoxicity ,Antibacterial activity ,Nuclear chemistry ,medicine.drug - Abstract
New indole derivatives of fusidic acid were synthesized by using the Fischer reaction. The obtained compounds were screened in vitro for antibacterial activity and were found to inhibit the growth of Staphylococcus aureus (MRSA, strain ATCC 43300) at concentrations comparable to fusidic acid. The obtained indole derivatives of fusidic acid were also characterized by relatively low cytotoxicity and minimal hemolytic effect at the highest concentration that was tested (32 μg/ml).
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- 2020
250. Understanding the risk of emerging bacterial resistance to over the counter antibiotics in topical sore throat medicines
- Author
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A. Shepard, R. Atkinson, O. Adegoke, Rebecca Wesgate, Jean-Yves Maillard, and C. Evangelista
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Cefotaxime ,medicine.drug_class ,Fusidic acid ,Antibiotics ,Nonprescription Drugs ,Microbial Sensitivity Tests ,Bacitracin ,Applied Microbiology and Biotechnology ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Antibiotic resistance ,Clavulanic acid ,Drug Resistance, Bacterial ,Tyrothricin ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,Bacteria ,030306 microbiology ,business.industry ,Pharyngitis ,General Medicine ,Amoxicillin ,chemistry ,Anti-Infective Agents, Local ,business ,Biotechnology ,medicine.drug - Abstract
Aims\ud \ud The aims of this study were to explore the development of bacterial resistance and cross‐resistance in four common human pathogens following realistic exposure to antibiotics found in over‐the‐counter (OTC) sore throat medicines: gramicidin, neomycin, bacitracin and tyrothricin.\ud Methods and Results\ud \ud Bacterial exposure to in‐use (concentration in the product before use) and diluted concentration (i.e. during use ) of antibiotic where conducted in broth for 24 h or until growth was visible. The changes in bacterial susceptibility profile before and after exposure was determined using standardized ISO microdilution broth. Antibiotic testing was performed according to EUCAST guidelines. We demonstrated that test bacteria were able to survive exposure to the in‐use concentrations of some antibiotics used in OTC medicines. Exposure to during use concentrations of bacitracin resulted in stable increase in minimal inhibitory concentration (MIC) (>8‐fold) in Staphylococcus aureus and Acinetobacter baumannii . Exposure to tyrothricin resulted in a stable increase in MIC (2·4‐fold) in Klebsiella pneumoniae , and exposure to neomycin resulted in a stable increase MIC (5000‐fold higher than the baseline) in Streptococcus pyogenes . Clinical cross‐resistance to other antibiotics (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid and cefotaxime) was also demonstrated following exposure to bacitracin or tyrothricin. Bacitracin exposure lead to a stable bacterial resistance after 10 passages.\ud Conclusions\ud \ud Our results indicate that OTC antibiotic medicines have the potential to drive resistance and cross‐resistance in vitro .\ud Significance and Impact of the Study\ud \ud Tackling antibiotic resistance is a high worldwide priority. It is widely accepted that the overuse and misuse of antibiotics increase the risk of the development and spread of antibiotic resistance within communities. A number of OTC sore throat products, widely available across the world for topical use in respiratory indications, contain locally delivered antibiotics. Our findings showed that these antibiotics in OTC medicines present a risk for emerging cross‐resistance in a number of bacterial respiratory pathogens.
- Published
- 2020
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