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ACS Omega Aug 2023In this study, hydrogels containing 2-hydroxyethyl methacrylate (HEMA), Eudragit L-100, and fusidic acid in different compositions were prepared with the confinement...
In this study, hydrogels containing 2-hydroxyethyl methacrylate (HEMA), Eudragit L-100, and fusidic acid in different compositions were prepared with the confinement method by using ammonium persulfate (APS) as a chemical initiator and ethylene glycol dimethacrylate (EGDMA) as a cross-linker to determine the most suitable formulation for use in eczema treatment. Fusidic acid (FA)-confined HEMA/Eudragit L-100 in synthesis of the hydrogel was used with the Taguchi method, and the optimum synthesis conditions were determined. The swelling percentages of the hydrogels were calculated in different pH environments and distilled water. Also, the cream formulations developed and contained in chitosan and HEMA-based polymers were synthesized. Viscosity and pH values changed between 30,000 and 100,000 cP and between 5 and 6 for different cream formulations with various conditions, respectively. Also, swelling percentages of hydrogels were between 20 and 40. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses were performed to characterize the hydrogel structure and the cream formulations. In addition, the stability of the formulations to 28 days and the changes in parameters such as appearance, centrifugation, pH, relative density, viscosity, spreading were evaluated, comparatively.
PubMed: 37546649
DOI: 10.1021/acsomega.3c02833 -
Membranes Mar 2023Fusidic acid (FA) is an antibiotic with high activity against ; it has been used in clinical practice since the 1960s. However, the narrow antimicrobial spectrum of FA...
Fusidic acid (FA) is an antibiotic with high activity against ; it has been used in clinical practice since the 1960s. However, the narrow antimicrobial spectrum of FA limits its application in the treatment of bacterial infections. In this regard, this work aims both at the study of the antimicrobial effect of a number of FA amines and at the identification of their potential biological targets. In this way, FA analogues containing aliphatic and aromatic amino groups and biogenic polyamine, spermine and spermidine, moieties at the C-3 atom, were synthesized (20 examples). Pyrazinecarboxamide-substituted analogues exhibit a high antibacterial activity against (MRSA) with MIC ≤ 0.25 μg/mL. Spermine and spermidine derivatives, along with activity against , also inhibit the growth and reproduction of Gram-negative bacteria , , and , and have a high fungicidal effect against and . The study of the membrane activity demonstrated that the spermidine- and spermine-containing compounds are able to immerse into membranes and disorder the lipidsleading to a detergent effect. Moreover, spermine-based compounds are also able to form ion-permeable pores in the lipid bilayers mimicking the bacterial membranes. Using molecular docking, inhibition of the protein synthesis elongation factor EF-G was proposed, and polyamine substituents were shown to make the greatest contribution to the stability of the complexes of fusidic acid derivatives with biological targets. This suggests that the antibacterial effect of the obtained compounds may be associated with both membrane activity and inhibition of the elongation factor EF-G.
PubMed: 36984696
DOI: 10.3390/membranes13030309 -
Scientific Reports Apr 2021While many data on molecular epidemiology of MRSA are available for North America, Western Europe and Australia, much less is known on the distribution of MRSA clones...
While many data on molecular epidemiology of MRSA are available for North America, Western Europe and Australia, much less is known on the distribution of MRSA clones elsewhere. Here, we describe a poorly known lineage from the Middle East, CC1153, to which several strains from humans and livestock belong. Isolates were characterised using DNA microarrays and one isolate from the United Arab Emirates was sequenced using Nanopore technology. CC1153 carries agr II and capsule type 5 genes. Enterotoxin genes are rarely present, but PVL is common. Associated spa types include t504, t903 and t13507. PVL-positive CC1153-MSSA were found in Egyptian cattle suffering from mastitis. It was also identified among humans with skin and soft tissue infections in Saudi Arabia, France and Germany. CC1153-MRSA were mainly observed in Arabian Gulf countries. Some isolates presented with a previously unknown SCCmec/SCCfus chimeric element in which a mec B complex was found together with the fusidic acid resistance gene fusC and accompanying genes including ccrA/B-1 recombinase genes. Other isolates carried SCCmec V elements that usually also included fusC. Distribution and emergence of CC1153-MRSA show the necessity of molecular characterization of MRSA that are resistant to fusidic acid. These strains pose a public health threat as they combine resistance to beta-lactams used in hospitals as well as to fusidic acid used in the community. Because of the high prevalence of fusC-positive MRSA in the Middle East, sequences and descriptions of SCC elements harbouring fusC and/or mecA are reviewed. When comparing fusC and its surrounding regions from the CC1153 strain to available published sequences, it became obvious that there are four fusC alleles and five distinct types of fusC gene complexes reminiscent to the mec complexes in SCCmec elements. Likewise, they are associated with different sets of ccrA/B recombinase genes and additional payload that might include entire mec complexes or SCCmec elements.
Topics: Animals; Bacterial Proteins; Cattle; Drug Resistance, Bacterial; Fusidic Acid; Humans; Interspersed Repetitive Sequences; Methicillin-Resistant Staphylococcus aureus; Middle East; Nanopore Sequencing; Oligonucleotide Array Sequence Analysis; Phylogeny; Sequence Analysis, DNA; Whole Genome Sequencing
PubMed: 33854075
DOI: 10.1038/s41598-021-86273-4 -
Canadian Medical Association Journal Apr 1980The extensive foreign experience with fusidic acid prior to its belated introduction to Canada is reviewed. Fusidic acid is a steroid antibiotic with minimal toxic and... (Review)
Review
The extensive foreign experience with fusidic acid prior to its belated introduction to Canada is reviewed. Fusidic acid is a steroid antibiotic with minimal toxic and hormonal effects that is mainly excreted through the liver. It has a predominantly bactericidal action and does not shown cross-resistance with other antibiotics. Since organisms resistant to this drug form easily in vitro when exposed to low concentrations, complementary treatment with another antibiotic may be required in some clinical situations. Although fusidic acid is active in vitro against a number of organisms, to date it has mainly been used to treat serious infections due to Staphylococcus aureus. The agent appears to be particularly valuable in the treatment of bone and joint infections and in pediatric practice. Fusidic acid will soon be available in Canada for both oral and intravenous administration. Attainable antibiotic levels in many tissues and body fluids greatly exceed the minimum inhibitory concentrations.
Topics: Anti-Bacterial Agents; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Fusidic Acid; Humans; Liver; Staphylococcal Infections
PubMed: 6988070
DOI: No ID Found -
Clinical Infectious Diseases : An... Aug 2012Recent reports of reduced response to standard therapies for Clostridium difficile infection (CDI) and the risk for recurrent CDI that is common with all currently... (Review)
Review
Recent reports of reduced response to standard therapies for Clostridium difficile infection (CDI) and the risk for recurrent CDI that is common with all currently available treatment agents have posed a significant challenge to clinicians. Current recommendations include metronidazole for treatment of mild to moderate CDI and vancomycin for severe CDI. Results from small clinical trials suggest that nitazoxanide and teicoplanin may be alternative options to standard therapies, whereas rifaximin has demonstrated success in uncontrolled trials for the management of multiple recurrences. Anecdotal reports have also suggested that tigecycline might be useful as an adjunctive agent for the treatment of severe complicated CDI. Reports of resistance will likely limit the clinical use of fusidic acid and bacitracin and, possibly, rifaximin if resistance to this agent becomes widespread. Treatment of patients with multiple CDI recurrences and those with severe complicated CDI is based on limited clinical evidence, and new treatments or strategies are needed.
Topics: Anti-Bacterial Agents; Bacitracin; Clinical Trials as Topic; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Fusidic Acid; Humans; Metronidazole; Nitro Compounds; Secondary Prevention; Severity of Illness Index; Teicoplanin; Thiazoles; Treatment Outcome; Vancomycin
PubMed: 22752868
DOI: 10.1093/cid/cis355 -
CMAJ : Canadian Medical Association... Jun 2019
Topics: Administration, Cutaneous; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biopsy; Clobetasol; Diagnosis, Differential; Fusidic Acid; Humans; Male; Scalp Dermatoses; Skin Diseases, Vesiculobullous; Skin Neoplasms
PubMed: 31209134
DOI: 10.1503/cmaj.181685 -
British Journal of Pharmacology Sep 19711. By combining the agar plate diffusion technique for determination of antibiotic activity and zone microelectrophoresis in agar gel, the activity of fusidic acid in...
1. By combining the agar plate diffusion technique for determination of antibiotic activity and zone microelectrophoresis in agar gel, the activity of fusidic acid in individual serum proteins of blood and pus obtained from patients given sodium fusidate revealed albumin to be responsible for the protein binding of this antibiotic.2. Based on the assumption that only free fusidic acid is microbiologically active, the relationship between the concentration of albumin and the ratio of free to total fusidic acid was determined at four concentrations of free fusidic acid, using as test organisms four differently sensitive variants of a Staphylococcus aureus strain. At each concentration an increasing amount of albumin (0-40 mg/ml culture medium) decreased the activity of fusidic acid as determined in serial dilutions (IC50).3. The law of mass action expressed as Langmuir's adsorption isotherm was valid if a correction for the influence of albumin on the sensitivity of the strain of Staph. aureus was introduced. For other test organisms no correction is necessary. The constant in Langmuir's adsorption isotherm was K=78400+/-8200 l./mol and n=3.15 (95% confidence limits: 2.09-5.52).4. The mean blood concentration was 20.8 mug/ml and the mean pus concentration 17.2 mug/ml in nineteen sets of blood and pus samples. The ratio of pus to blood corresponds to the ratio of published values for the protein concentrations in serum and in inflammatory oedema.5. It is concluded that for albumin bound drugs the ;storage depot' of the organism also includes the fluid of the tissue spaces including the inflammatory oedema. As recent studies have revealed an extravascular albumin pool similar in size to the plasma pool, this ;storage depot' should not be neglected.
Topics: Agar; Blood Protein Electrophoresis; Blood Proteins; Drug Interactions; Fusidic Acid; Gels; Humans; Kinetics; Models, Chemical; Protein Binding; Serum Albumin; Staphylococcus; Suppuration
PubMed: 5136455
DOI: 10.1111/j.1476-5381.1971.tb07164.x -
Allergy & Rhinology (Providence, R.I.) Jan 2016To examine the effects, after septoplasty, of local antibiotic pomades as an alternative to prophylactic antibiotic use, which is a controversial matter among the...
AIM
To examine the effects, after septoplasty, of local antibiotic pomades as an alternative to prophylactic antibiotic use, which is a controversial matter among the otolaryngologists, on nasal flora and bacterial growth.
MATERIAL AND METHOD
Nasal packings placed after septoplasty surgery to provide septal stabilization and bleeding control pose a risk in terms of infection. In this study, 106 patients, who were examined by comparing mupirocin- and fusidic acid-soaked packings and antibiotic-free packings, were divided into three groups. Nasal cultures were obtained from each patient twice, before the surgery and on the second day immediately after the packings were removed, and the culture results were statistically compared.
RESULTS
In the mupirocin group (group 2), postoperative normal flora growth rate was significantly higher than in the fusidic acid group (group 3) and the antibiotic-free group (group 1) (p < 0.024). In the mupirocin group (group 2), the gram-positive growth rate in the postoperative period showed a significant decrease when compared when the preoperative period (p < 0.05) (5.7%). In the fusidic acid group (group 3), the postoperative gram-positive rate showed a significant decrease compared with the preoperative period (p < 0.05). In group 2, the postoperative methicillin-resistant Staphylococcus aureus rate showed a significant decrease than in the preoperative period (2.9%) (p < 0.05). Similarly, in group 3, the postoperative methicillin-resistant S. aureus rate showed a significant decrease compared with that of the preoperative period (11.1%) (p < 0.05).
CONCLUSION
Use of mupirocin- and fusidic acid-soaked nasal packings after septoplasty significantly decreased, especially, postoperative gram-positive bacterial growth in nasal cultures. Although systemic antibiotherapy was not administered, the lack of local and systemic infection findings was an important result that we obtained in terms of clinical use. Usage advantages of mupirocin and fusidic acid soaked packings are an easily applicable, cost-effective, and safe method.
PubMed: 28683247
DOI: 10.2500/ar.2016.7.0181 -
International Journal of Molecular... Jul 2021Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and...
Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC 7.4 ± 0.7 μM) and colon cancer HT29 (IC 9.0 ± 0.4 μM). Notably, spin-labelled fusidic acid derivative acts strongly against these two cancer cell lines (PC3: IC 6.0 ± 1.1 μM; HT29: IC 7.4 ± 0.6 μM). Additionally, another fusidic acid analogue was also found to be active towards HT29 with IC 7.0 ± 0.3 μM (CV). Studies on the mode of action revealed that compound increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound was successfully achieved, since mitochondria are the major source of ROS generation.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cholic Acid; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Fusidic Acid; Humans; Neoplasms; Pentacyclic Triterpenes; Small Molecule Libraries; Spin Labels; Steroids; Triterpenes; Betulinic Acid
PubMed: 34281176
DOI: 10.3390/ijms22137125 -
Gels (Basel, Switzerland) Apr 2022Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The...
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.
PubMed: 35448146
DOI: 10.3390/gels8040245