Search

Background: Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease. Tetracyclines are one of the few therapeutic options recommended for mild‐to‐moderate disease. This study aimed to investigate the efficacy of systemic fusidic acid's (FA) effectiveness in treating HS. Methods: This retrospective study analyzed 55 FA therapy cycles (TC, average weekly dose: 6409 mg; range: 5250–9800 mg; 2–12 weeks) in 49 patients. The outcome was evaluated using the Physician's Global Assessment (PGA) scale. Therapy response was defined as any reduction of inflammatory activity without the occurrence of flares. We also characterized adverse events and investigated predictors for treatment success. Results were compared to a matched control group receiving doxycycline. Results: FA treatment (55 treatment cycles (TC); male: 45.5%; female: 54.5%) showed an overall response rate of 70.9% (39 TC). No worsening was observed. Significantly higher response rates were observed in females (83.3%, P = 0.026) and Hurley I (90.9%, P = 0.008). After multivariate adjustment, higher response rates were associated with the Hurley grade (P = 0.046) but not with gender (P = 0.0174). Adverse reactions (21.8% gastrointestinal symptoms) occurred in 27.3% (15 TC) and 46.7% within the first 4 weeks. Similar results were observed in the doxycycline control group (overall response rate: 76.4%). Conclusion: Oral FA is safe and improves symptoms in most patients. HS patients could benefit from oral FA treatment, especially in case of contraindications or resistance to tetracyclines. [ABSTRACT FROM AUTHOR]

The present work is concerned with the novel, accurate, and precise quantification of beclomethasone dipropionate and fusidic acid in combination (cream), which was performed using high-performance thin-layer chromatography (HPTLC), and validation was performed based on International Council for Harmonization guidelines (Q2 R1). A series of HPTLC tests was conducted on pre-coated silica gel G60 F254 plates as the stationary phase and n-hexane:ethyl acetate:toluene:diethyl ether (4.5:5.5:1:0.2, v/v/v/v) as the mobile phase. Chamber saturation time was 30 min to attain the desired results. The Rf of beclomethasone dipropionate and fusidic acid was determined to be 0.52 and 0.36 respectively. The densitometric estimation was performed in reflectance mode at 238 nm. A linear relationship was seen in the range of 0.4–2.0 μg/band for beclomethasone dipropionate and 0.8–4.0 μg/band for fusidic acid with R2 of 0.9914 and 0.9927 for beclomethasone dipropionate and fusidic acid respectively. The limit of detection was found to be 0.2653 and 0.27040 for beclomethasone dipropionate and fusidic acid respectively, and the limit of quantification was found to be 0.42065 and 0.81940 for beclomethasone dipropionate and fusidic acid respectively. The percentage recovery was found to be within the range 98–102% for both beclomethasone dipropionate and fusidic acid. The method proposed was determined to be novel, error-free, robust, and reproducible. [ABSTRACT FROM AUTHOR]

In continuation of our studies on modification of fusidane triterpenoids, the alkynyl moieties were introduced into fusidic acid to synthesize new compounds promising as antimicrobial and antitumor agents. Transformations of the triple bond via the CuI-catalyzed reactions afforded new 1,2,3-triazoles as well as mono- and diacetylenic derivatives. [ABSTRACT FROM AUTHOR]

Abstract The antibiotic fusidic acid (FA) is used to treat Staphylococcus aureus infections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing its release from the ribosome after translocation. While FA, due to permeability issues, is only effective against gram-positive bacteria, the available structures of FA-inhibited complexes are from gram-negative model organisms. To fill this knowledge gap, we solved cryo-EM structures of the S. aureus ribosome in complex with mRNA, tRNA, EF-G and FA to 2.5 Å resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 Å resolution. With both FA variants, the majority of the ribosomal particles are observed in chimeric state and only a minor population in post-translocational state. As expected, FA binds in a pocket between domains I, II and III of EF-G and the sarcin-ricin loop of 23S rRNA. FA-CP binds in an identical position, but its cyclopentane moiety provides additional contacts to EF-G and 23S rRNA, suggesting that its improved resistance profile towards mutations in EF-G is due to higher-affinity binding. These high-resolution structures reveal new details about the S. aureus ribosome, including confirmation of many rRNA modifications, and provide an optimal starting point for future structure-based drug discovery on an important clinical drug target.

Dunia A Alzahrani,1 Khulud A Alsulami,1 Fatemah M Alsulaihem,1 Abrar A Bakr,1 Rayan Y Booq,2 Ahmed J Alfahad,3 Alhassan H Aodah,1 Samar A Alsudir,4 Amany A Fathaddin,5,6 Essam J Alyamani,2 Aliyah A Almomen,7 Essam A Tawfik1 1Advanced Diagnostics and Therapeutics Technologies Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 2Wellness and Preventative Medicine Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 3Waste Management and Recycling Technologies Institute, Sustainability and Environment Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 4Bioengineering Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 5Department of Pathology, College of Medicine, King Saud University, Riyadh, 12372, Saudi Arabia; 6King Saud University Medical City, Riyadh, 12372, Saudi Arabia; 7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Essam A Tawfik, Email etawfik@kacst.gov.saIntroduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization.Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds.Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 μg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 μg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 μg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 μg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups.Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.Keywords: diabetes mellitus, diabetic foot ulcers, nanofibers, electrospinning, drug delivery, wound healing, moxifloxacin, fusidic acid, pirfenidone

The ability to formulate optimum drug-loaded carriers is a challenge that impedes virtuous drug delivery and stability. Nano micelles (NMs) are highly prospective carriers due to their minute dimensions and exceptional biocompatibility. This study investigated a more efficient and straightforward fabrication method for surfactant nano micelles than the conventional solvent vaporization process. The objective was to develop and validate the Direct Method, an expedited approach for producing surfactant NMs. Tween 20, was employed to simulate the solubility of various drugs in Surfactant, including azithromycin monohydrate, fusidic acid, and metronidazole. Four distinct concentrations of the medication were employed. The polydispersity index and micellar diameter were employed to compare and contrast the two methodologies. No significant differences (p < 0.05) were observed between the outcomes obtained from both methods, irrespective of the concentrations of the drugs. The Direct Method exhibited comparable levels of efficiency to the conventional approach. The study effectively established the Direct Method as a rapid and efficient substitute for surfactant NMs synthesis. [ABSTRACT FROM AUTHOR]

Abstract Background Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). Objectives This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. Methods The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. Results Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. Conclusion The current findings highlight FA’s potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box–Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system. [ABSTRACT FROM AUTHOR]

Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with –3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations. [ABSTRACT FROM AUTHOR]

Background: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). Objectives: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. Methods: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. Results: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. Conclusion: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

Aim: We aimed to detect the frequency of methicillin-resistant Staphylococcus aureus (MRSA) strains that were isolated from wound infections in our hospital, and then we want to evaluate the in vitro fusidic acid (FA) susceptibility rates of them to determine the place of FA in empirical treatment. Material and Method: A total of 110 S. aureus strains, which were isolated from wound culture samples from various services and outpatients, were included in the study. The bacteria were identified and antibiogram using our microbiology laboratory's classical methods and VITEK 2 (Biomerieux, France) system. Methicillin sensitivity was evaluated according to Clinical and Laboratory Standards Institute (CLSI) criteria, and Fusidic acid sensitivity was assessed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The data were recorded in the IBM Statistical Package for Social Sciences (SPSS) program version 17, statistical analyses were performed, and P <0.05 was considered significant. Results: 51 (46.4%) of S. aureus were isolated from service patients, and 59 (53.6%) were separated from outpatient clinics. The total methicillin resistance of 110 S. aureus strains was 20.9%. Methicillin resistance in outpatient clinics and services was 17.4% and 23.72%, respectively; their difference was not statistically significant (P >0.05). Sensitivity rates of FA in the outpatient clinics and services were found to be 90.2% and 94.9%, respectively, and the difference was not statistically significant (P >0.05). Methicillin-resistant Staphylococcus aureus was primarily isolated from pediatrics, orthopedics, general surgery, and otorhinolaryngology. In these units, FA sensitivities were 93.7%, 96.1%, 100%, and 100%, respectively. Conclusion: FA should be considered an effective and safe empirical treatment option in treating soft tissue and wound infections caused by community and hospital-acquired MRSA. [ABSTRACT FROM AUTHOR]

New nitrogen-containing fusidic acid analogues, namely bis-amidoxime, bis-tetrazole, and 1,2,4-oxadiazoles, were synthesized via chemical transformations of 3,11-bis-O-(2-cyanoethyl)fusidic acid methyl ester. [ABSTRACT FROM AUTHOR]

The CO2 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. [ABSTRACT FROM AUTHOR]

Objective To evaluate the in vitro antimicrobial activities of 16 common agents against Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis to provide data for the rational clinical use of drugs. Methods From 1st January to 31st December in 2019, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis were collected from 24 hospitals in 18 provinces in China. Antimicrobial susceptibility testing was conducted by automated instrumentation method, and WHONET 5.6 software was used to calculate the drug sensitivity results of the strains to 16 antibacterial drugs including vancomycin, norvancomycin, fusidic acid and linezolid. Results A total of 255 strains of Staphylococcus aureus, 117 strains of Enterococcus faecalis and 114 strains of Enterococcus faecium were collected. Blood was the most common specimen type (22.2%, 108/486), followed by urine (18.9%, 82/486). According to the drug sensitivity results, vancomycin, norvancomycin, linezolid and teicoplanin maintained high activity to all strains. All Staphylococcus aureus and Enterococcus faecalis were sensitive to vancomycin and teicoplanin, while the resistance rates of vancomycin and teicoplanin against Enterococcus faecium were 4.4% and 2.6%, respectively. The resistance rates of linezolid against Staphylococcus aureus, Eenterococcus faecium and Eenterococcus fascalis were 0, 0 and 4.3%, respectively. Norvancomycin and vancomycin showed similar antibacterial activity against Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis, with 50% minimum inhibitory concentration (MIC50) of 1 mg/L, and MIC90 of 2 mg/L. The isolation rate of methicillin-resistant Staphylococcus aureas(MRSA) was 35.7%, with 13.2% resistance to fusidic acid and 3.0% in methicillin-susceptible Staphylococcus aureas. Conclusions The activity of the 16 antimicro-bial drugs against Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis varied considerably. The data will provide reference for the rational use of antimicrobial drugs.

Fusidic acid and betamethasone are two pharmaceutically active compounds found in topical dosage forms. Sometimes, they can unintentionally wind up in surface water via skin washing. Therefore, a stochastic platform based on a type of calix[4]arene and polyaniline modified screen-printed electrode was developed for their on-site analysis. For both analytes, remarkably wide dynamic ranges (1.0 × 10−17–1.0 × 10−4 for fusidic acid, and 1.0 × 10−18–1.0 × 10−3 for betamethasone) and considerably low limits of quantitation (1.0 × 10−17 for fusidic acid, and 1.0 × 10−18 for betamethasone) were attained. Moreover, the proposed platform was successfully applied to real samples such as topical dosage form and surface water, obtaining recovery values higher than 90.0 % with relative standard deviation values below 0.1 %.

The increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria and comparatively limited options of antibiotics pose a major threat to public health worldwide. Polymyxin B is the last resort against extensively resistant Gram-negative bacterial infections. However, a large number of Gram-negative bacteria exhibited high-level resistance to Polymyxin B, bringing challenges for antimicrobial chemotherapy. Combination therapies using polymyxins and other antibiotics are recommended to treat multidrug-resistant pathogens. In this study, we selected Gram-negative bacterial strains, including Klebsiella pneumoniae and Escherichia coli, to explore whether fusidic acid and polymyxin B have a synergistic killing effect. Through broth microdilution, we observed that minimum inhibitory concentrations (MICs) against polymyxin B in the isolates tested were significantly reduced by the addition of fusidic acid. Notably, chequerboard analysis indicated a synergistic effect between polymyxin B and fusidic acid. In addition, subsequent time-kill experiments showed that the combination of polymyxin B and fusidic acid was more effective than a single drug in killing bacteria. Finally, our investigation utilizing the murine model revealed a higher survival rate in the combination therapy group compared to the monotherapy group. Our research findings provide evidence of the synergistic effect between polymyxin B and fusidic acid. Fusidic acid was shown to increase the sensitivity of multi-drug resistant E. coli and K. pneumoniae to polymyxin B, thereby enhancing its bactericidal activity. This study provides new insights into a potential strategy for overcoming polymyxin B resistance, however, further investigations are required to evaluate their feasibility in real clinical settings. [ABSTRACT FROM AUTHOR]

The combination of herbal drugs with a topical antibacterial for managing a chronic disease like acne vulgaris has emerged lately to settle side effects and bacterial multidrug resistance. Mixed micelles (MMs) incorporated into nanogel were explored for hybrid delivery of curcumin (Cur) and fusidic acid (FA) combination presenting a multi-strategic treatment. Curcumin-fusidic acid–loaded mixed micelles (Cur-FA-MMs) were assessed for size, surface charge, compatibility, in vitro release, and encapsulation. The selected formula was further loaded into nanogel and investigated for viscosity, ex vivo permeation, and in vivo potential. Cur-FA-MMs exhibited uniform nanosized spherical morphology, and negative surface charge affording high encapsulation for both drugs with a biphasic in vitro release over a period of 48h and good colloidal stability. The attained Cur-FA-MM-loaded nanogel had optimum viscosity with remarkable permeation coefficient values nearly 2-fold that related to plain nanogel. The pharmacodynamic effect of Cur on FA was pronounced by the significant improvement of the skin's degree of inflammation, epidermal hypertrophy, and congestion in animals treated with Cur-FA-MM-loaded nanogel. In conclusion, micellar nanogel could enable the progressive effect of Cur (an antioxidant with reported antibiotic activity) on FA (antibiotic) and decrease the risk of emerging antibiotic resistance by enhancing the solubility and permeation of Cur. [ABSTRACT FROM AUTHOR]

Objective We investigated the effects of fusidic acid (FA) on human cervical, thyroid, and breast carcinoma cell lines to determine the potential usefulness of FA in cancer treatment. Methods Six cancer cell lines (cervical cancer: Caski, HeLa; thyroid cancer: 8505C, TPC1; and breast cancer: MCF-7, MDA-MB-231) were treated with FA. Furthermore the changes in cell growth, cell cycle duration, and extent of apoptosis were analyzed. Results After FA treatment, the cancer cells showed a decrease in growth rate. In the cell death assay, the cell populations were similar in each cell type after treatment with FA, indicating that growth inhibition by FA was not related to the induction of apoptosis. FA induced cell cycle arrest at a dose that inhibited growth rate, which varied in different cell types. G0/G1 phase arrest occurs in breast cancer, S phase arrest in 8505C thyroid cancer, and G2/M phase arrest in cervical cancer. These results indicate that FA reduces growth rates by inducing cell cycle arrest. Conclusion FA treatment can interfere with cell proliferation by inducing cell cycle arrest in human cervical, thyroid, and breast carcinoma cell lines. Thus, FA can be useful in treating human cervical, thyroid, and breast carcinomas.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box–Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system.

Nanomaterials manufactured of amphiphilically‐altered polysaccharides have sparked a great deal of interest due to their capability to elevate drug transport across the skin. The study presents the fabrication of alkylated chitosan through 2‐tert‐butoxymethyloxirane alteration (alkylation degree 29.7%), that was typified by spectroscopic, chromatographic, and thermal analysis approaches before being constructed into nanomaterials for the analysis of their capability in governing fusidic acid diffusion percutaneously. The nanomaterials were constructed via the ionic interaction of positively charged chitosan and negatively charged cross linker sodium tripolyphosphate, with a loading degree of fusidic acid of ca. 20% reported. Fusidic acid release was slower in nanomaterials constructed of alkylated chitosan than in neat chitosan. Under application‐relevant conditions, in vitro incubation with HaCaT cells exhibited insignificant toxicity. Using Franz diffusion cells, the alkylated chitosan nanomaterials induced fusidic acid to infiltrate the Strat‐M® membrane at a 2‐fold greater rate than the neat chitosan nanomaterials. Based on the agar diffusion test, fusidic acid was shown to have better antimicrobial activity when loaded into alkylated chitosan nanomaterials than when loaded into neat chitosan nanomaterials. Ultimately, the in vitro results revealed that alkylated chitosan nanomaterials offer a great deal of potential for percutaneous delivery, which merits greater analysis. [ABSTRACT FROM AUTHOR]

Purpose: Microemulsions (MEs) are homogeneous, optically clear and thermodynamically stable systems intended to increase the bioavaibility, solubility, and entrapment of drugs. In this study, a new system of oil-in-water MEs was formulated with Fusidic acid as a drug. MEs were composed of Isopropyl myristate, non-ionic surfactants tween 80, 1-propanol and water. Methods: The optimum weight ratios of components and MEs areas were determined by pseudoternary phase diagram. The prepared microemulsions were evaluated regarding their stability, pH, refractive index, conductivity, viscosity, particle size, zeta potential, surface tension and partition coefficient. Results: These parameters suggested that the optimized MEs were stable and optically clear. Conclusion: This study reveals that the product can be used for ocular treatment. [ABSTRACT FROM AUTHOR]

Background: Analytical techniques are a crucial method used in quality control procedures. Fusidic acid (FU), an antibacterial drug, is available on the market in a semisolid dosage form. This work aimed to develop a simple, sensitive, and robust UPLC assay for FU. Method: The effect of the formic acid concentration (X1 (1%, 0.55%, and 0.1%)), and column temperature (X2 (40, 32.5, and 25 °C)) on the retention time, peak area, and peak height were determined. Results: The results show that a long retention time of 1.18 min can be achieved with a low column temperature and a low to medium concentration of formic acid. A good peak height resolution was obtained with a low concentration of formic acid at different temperature settings. The optimized condition was suggested by the software program to analyze the drug in a mobile phase, consisting of 72% acetonitrile and 28% water containing 0.1% formic acid with a column temperature adjusted to 40 °C. Conclusion: The method was validated in terms of linearity, accuracy, precision, and robustness. In addition, the stability degradation study determined that the method can separate the drug from other degradation production. The method was applicable to determine the drug content in the marketed product. [ABSTRACT FROM AUTHOR]

Tight coordination between transcription and translation is crucial to maintaining the integrity of gene expression in bacteria, yet how bacteria manage to coordinate these two processes remains unclear. Possible direct physical coupling between the RNA polymerase and ribosome has been thoroughly investigated in recent years. Here, we quantitatively characterize the transcriptional kinetics of Escherichia coli under different growth conditions. Transcriptional and translational elongation remain coordinated under various nutrient conditions, as previously reported. However, transcriptional elongation was not affected under antibiotics that slowed down translational elongation. This result was also found by introducing nonsense mutation that completely dissociated transcription from translation. Our data thus provide direct evidence that translation is not required to maintain the speed of transcriptional elongation. In cases where transcription and translation are dissociated, our study provides quantitative characterization of the resulting process of premature transcriptional termination (PTT). PTT-mediated polarity caused by translation-targeting antibiotics substantially affected the coordinated expression of genes in several long operons, contributing to the key physiological effects of these antibiotics. Our results also suggest a model in which the coordination between transcriptional and translational elongation under normal growth conditions is implemented by guanosine tetraphosphate.

Niosomes are multilamellar vesicles that efficiently deliver active substance into skin systemic circulation or skin layers. They are used in topical drug delivery system to enhance the skin permeation of active substance. So, the prime objective of this study was to develop a niosomal gel of fusidic acid to increase its skin permeation. Different formulations of niosomes of fusidic acid were designed by varying the cholesterol to surfactant ratio. Formulations containing fusidic acid, cholesterol, dihexadecyl pyridinium chloride, Span 60, or Tween 60 were prepared by thin film hydration method in rotary evaporator. The thin film formed in rotary flask was hydrated by phosphate buffer saline of pH 7.2. The niosomes formed were characterized through entrapment efficiency, size, polydispersity index (PDI), and zeta potential. The S3 formulation containing span 60 showed the highest entrapment efficiency (EE) of niosomes, so it was incorporated into Carbopol gel. Determination of pH, spreadability, rheological, and ex vivo permeation studies was conducted of niosomal gel. The results of ex vivo permeation studies showed high permeation of fusidic acid when gel was applied to an albino rat skin. According to the results and previous studies of niosomes, it can be concluded that niosomes enhanced the permeation of fusidic acid through the skin.

Background: Masquelet technique is a two-stage surgical procedure used in the treatment of critical-size bone defects (CSD). Adding antibiotics to polymethylmethacrylate (PMMA) is still questionable to create higher quality induced membrane (IM). The aim of the study was to evaluate the effects of three antibiotic-supplemented cement, fusidic acid, teicoplanin, and gentamicin, on osteogenesis and IM progression applied to rat femur CSD model by comparing histopathological, biochemical, and immunohistochemical findings.Methods: Twenty-eight male rats were divided into four groups control, gentamicin (G), teicoplanin (T), and fusidic acid (FA). A 10 mm CSD was created in rat femurs. In the postoperative 4th week, intracardiac blood samples were collected for biochemical analysis of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) levels. IMs obtained in secondary operation were fixed and prepared for histopathological scoring of membrane progression and immunohistochemical evaluation of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) expressions.Results: Levels of BALP and OC in serum didn't change among groups significantly while serum TNF-α levels significantly decreased in all antibiotic groups compared to the control group (P = 0.017). Histological scores of groups FA and T were significantly higher than those of groups Control and G (P = 0.0007). IMs of groups T and FA showed good progression while those of groups Control and G were also moderately progressed. A significant increase in TGF-β expression was observed in group G and FA (P = 0.001) while a significant increase in the expression of VEGF was observed in groups G and T compared to the control group (P = 0.036).Conclusions: The bone cement impregnated with thermostable and safe antibiotics, gentamicin, fusidic acid, and teicoplanin can increase osteogenesis and support IM progression by increasing the expressions of TGF-β and VEGF. Anabolic effects of induced membranes used in the treatment of critical-size bone defects can be enhanced by antibiotic-supplemented PMMAs applied by altering the original technique. [ABSTRACT FROM AUTHOR]

The CO2 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-skin-phenotype 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.

Shuying Chen,&ast; Lulin Rao,&ast; Chunchan Lin Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunchan Lin, Email wyyylcc@163.comPurpose: Fusidic acid (FA), a potent steroidal antibiotic, is used topically to treat skin and soft tissue infections (SSTIs) caused by Staphylococci. The aim of this study is to report the prevalence of fusidic acid resistance among Staphylococcus epidermidis clinical isolates from a tertiary hospital in Wenzhou, east China.Methods: The antibiotic susceptibility of S. epidermidis isolates was determined by disc diffusion method and agar dilution method. Then, FA-resistant S. epidermidis isolates were characterized by multi-locus sequence typing, SCCmec typing and pulsed-field gel electrophoresis.Results: In the present study, the 55 (7.7%) FA-resistant S. epidermidis among 711 S. epidermidis clinical isolates were isolated from different parts of 53 patients. Fifty-five FA-resistant S. epidermidis isolates with FA MIC values ranged from 4 to 32 μg/mL. Among them, 50 (90.9%) were identified as methicillin-resistant Staphylococcus epidermidis (MRSE), in which mecA were positive. Meanwhile, the positive rates of fusB and fusC genes among FA-resistant S. epidermidis isolates were 85.5% (47/55) and 7.3% (4/55), respectively. All 55 isolates mentioned above were susceptible to vancomycin. More than 50% of FA-resistant isolates were resistant to non-β-lactam antimicrobials including erythromycin (80.0%, 44/55), clindamycin (65.5%, 36/55), ciprofloxacin (63.6%, 35/55) and sulfamethoxazole (63.6%, 35/55). A total of 14 sequence types (STs) were identified among the 55 FA-resistant S. epidermidis isolates, of which, ST2 (24/55, 43.6%) was the most predominant type. And the eBURST analysis showed that CC2, CC5 and CC247 accounted for 43.6% (24/55), 27.3% (15/55) and 14.5% (5/55), respectively. Meanwhile, a total of four SCCmec types (I, III, IV, V) were identified among the 55 FA-resistant S. epidermidis. Furthermore, the pulsed field gel electrophoresis divided the 55 isolates into 20 types, namely A-T. Q-type strains were most prevalent, accounting for 30.9% (17/55).Conclusion: Taken together, the dissemination of S. epidermidis ST2 clone with FA resistance can cause trouble in controlling S. epidermidis infections.Keywords: Staphylococcus epidermidis, fusidic acid, resistance, molecular characteristics

Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report. FA and its active metabolite (3-keto FA) were measured in plasma and cerebrospinal fluid (CSF) to assess the treatment of FA, and the results indicated that 1,500 mg per day of FA was sufficient to achieve therapeutic concentrations in both plasma and CSF in intracranial infection patients, while the dosage did not experience unexpected regimen-related toxicity. [ABSTRACT FROM AUTHOR]

Niosomes are multilamellar vesicles that efficiently deliver active substance into skin systemic circulation or skin layers. They are used in topical drug delivery system to enhance the skin permeation of active substance. So, the prime objective of this study was to develop a niosomal gel of fusidic acid to increase its skin permeation. Different formulations of niosomes of fusidic acid were designed by varying the cholesterol to surfactant ratio. Formulations containing fusidic acid, cholesterol, dihexadecyl pyridinium chloride, Span 60, or Tween 60 were prepared by thin film hydration method in rotary evaporator. The thin film formed in rotary flask was hydrated by phosphate buffer saline of pH 7.2. The niosomes formed were characterized through entrapment efficiency, size, polydispersity index (PDI), and zeta potential. The S3 formulation containing span 60 showed the highest entrapment efficiency (EE) of niosomes, so it was incorporated into Carbopol gel. Determination of pH, spreadability, rheological, and ex vivo permeation studies was conducted of niosomal gel. The results of ex vivo permeation studies showed high permeation of fusidic acid when gel was applied to an albino rat skin. According to the results and previous studies of niosomes, it can be concluded that niosomes enhanced the permeation of fusidic acid through the skin. [ABSTRACT FROM AUTHOR]

The paper assesses the membranotropic action of the natural antibiotic fusidic acid (FA) and its derivatives. It was found that a FA analogue with ethylenediamine moiety (derivative 2), in contrast to native FA and 3,11-dioxime analogue (derivative 1), is able to increase the mobility of the lipid bilayer in the zone of lipid headgroups, as well as to induce permeabilization of lecithin liposome membranes. A similar effect of derivative 2 is also observed in the case of rat liver mitochondrial membranes. We noted a decrease in the microviscosity of the mitochondrial membrane and nonspecific permeabilization of organelle membranes in the presence of this agent, which was accompanied by a decrease in mitochondrial Δψ and OXPHOS efficiency. This led to a reduction in mitochondrial calcium retention capacity. The derivatives also reduced the production of H2O2 by mitochondria. The paper considers the relationship between the structure of the tested compounds and the observed effects.

Introduction: Fusidic acid (FA) has been widely applied in the clinical prevention and treatment of bacterial infections. Nonetheless, its clinical application has been limited due to its narrow antimicrobial spectrum and some side effects.Purpose: Therefore, it is necessary to explore the structure–activity relationships of FA derivatives as antibacterial agents to develop novel ones possessing a broad antimicrobial spectrum.Methods and result: First, a pharmacophore model was established on the nineteen FA derivatives with remarkable antibacterial activities reported in previous studies. The common structural characteristics of the pharmacophore emerging from the FA derivatives were determined as those of six hydrophobic centers, two atom centers of the hydrogen bond acceptor, and a negative electron center around the C-21 field. Then, seven FA derivatives have been designed according to the reported structure–activity relationships and the pharmacophore characteristics. The designed FA derivatives were mapped on the pharmacophore model, and the Qfit values of all FA derivatives were over 50 and FA-8 possessed the highest value of 82.66. The molecular docking studies of the partial target compounds were conducted with the elongation factor G (EF-G) of S. aureus. Furthermore, the designed FA derivatives have been prepared and their antibacterial activities were evaluated by the inhibition zone test and the minimum inhibitory concentration (MIC) test. The derivative FA-7 with a chlorine group as the substituent group at C-25 of FA displayed the best antibacterial property with an MIC of 3.125 µM. Subsequently, 3D-QSAR was carried on all the derivatives by using the CoMSIA mode of SYBYL-X 2.0.Conclusion: Hence, a computer-aided drug design model was developed for FA, which can be further used to optimize FA derivatives as highly potent antibacterial agents.

Objective: To develop a validated analytical method for simultaneous estimation of Fusidic acid and Beclomethasone dipropionate in pharmaceutical combined dosage form by HPLC. Method: A HPLC method was developed and validated for assay of Fusidic acid (FA) and Beclomethasone dipropionate (BD) in Topical pharmaceutical formulation. The chromatographic separation was achieved on Kromasil C18, 5µm (125 X 4.6 mm) column at ambient temperature of 250C, at a flow rate 2.5 mL/min using LC-2010 CHT Liquid Chromatography, Shimadzu HPLC system. Different mobile phases were used on trial and error basis for separation of two drugs. The final mobile phase selected for analysis comprised of mixture of Methanol, Ortho-Phosphoric acid and Acetonitrile in the ratio of 10:45:45% (v/v/v). Both the drugs showed maximum absorbance at 220 nm which was selected as the wavelength of detection throughout the experimental work. Validation of developed method was carried out according to ICH guidelines. Result: HPLC method was successfully developed for separation of FA and BD with good resolution. Method validation after assessment of various parameters indicated low % RSD within an acceptable limit of < 2.0%. Conclusion: The developed HPLC method for estimation of FA and BD is rapid, reliable, precise, and reproducible. [ABSTRACT FROM AUTHOR]

At present, high‐performance antibacterial polymer materials have attracted widespread attention, possessing huge application prospects in the fields of medical and biological science, and packaging. In this work, polydopamine nanoparticles (PDA NPs) with photothermal ability and active sites are designed to adsorb fusidic acid (FA) molecules with targeted antibacterial capability; then, polydopamine@fusidic acid (PDA@FA) is introduced into the polyurethane (PU) to obtain multifunctional and antibacterial PU materials (PUDA@FA). The structures and morphologies of PDA NPs and PDA@FA are successfully characterized by Fourier transform‐infrared spectroscopy and scanning electron microscopy. With the introduction of PDA@FA, the nano‐sized reinforcement not only greatly improves the mechanical properties (tensile strength 19.31 MPa and toughness 10.6 MJ m−3) of PU film but also due to the photothermal effect of PDA NPs and the antibacterial of FA, the scavenging activities of DPPH and ABTS reach 70–85% and 55–70%, respectively. The antibacterial rate of Staphylococcus aureus reaches more than 99.9% and presents long‐term antibacterial ability. In this way, this work provides new guidance for the preparation of high‐performance PU materials with both antibacterial and anti‐oxidation properties, broadening the application scope of antibacterial materials. [ABSTRACT FROM AUTHOR]

Adverse drug reactions of broad-spectrum fluoroquinolones or rifampicin are not uncommon during osteomyelitis and orthopaedic implant infections (OOII). Thus, we made an overview (i) of the prescription of fusidic acid (FA) and (ii) of FA susceptibility of Staphylococcus sp. and Cutibacterium sp. strains isolated from bone samples. All prescriptions of FA and all bone samples with positive culture for Staphylococcus sp. or Cutibacterium sp. (Reims University Hospital June 2017–May 2021) were included. All Staphylococcus aureus strains were considered as significant, whereas Coagulase-negative Staphylococcus and Cutibacterium spp. strains were not if these strains grew only on one sole sample. The antibiotic susceptibility of Staphylococcus sp. strains and the susceptibility to FA of Cutibacterium sp. strains had been determined using disk diffusion methods, as described for Staphylococcus sp. in the CASFM/EUCAST guidelines. The mean FA consumption was 0.6 daily defined doses/1000 patient days. FA was prescribed for OOII due to Staphylococcus sp. and Cutibacterium sp. in 24 and 2 cases, respectively. Among 401 Staphylococcus sp. strains, there were 254 S. aureus (63.3%), 84 methicillin-resistant (20.9%) and 333 FA-susceptible (83.0%) strains. S. aureus and methicillin-sensitive strains were more likely to be susceptible to FA (p < 0.001). Among 39 Cutibacterium sp. strains, the FA inhibition zone diameter geometric mean was 28.6 mm (24–35 mm), suggesting that all these strains could be considered as susceptible to FA. These data suggested that FA could be more frequently used in OOII due to Staphylococcus sp. and Cutibacterium sp., subject to the absence of other resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections. Methods: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months. Results: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 μg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 μg/mL. Conclusion: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent. [ABSTRACT FROM AUTHOR]

Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781–1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives. [ABSTRACT FROM AUTHOR]