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PubMed2006

An antibacterial hydroxy fusidic acid analogue from Acremonium crotocinigenum.

A fusidane triterpene, 16-deacetoxy-7-beta-hydroxy-fusidic acid (1), was isolated from a fermentation of the mitosporic fungus Acremonium crotocinigenum. Full unambiguous assignment of all (1)H and (13)C data of 1 was carried out by extensive one- and two-dimensional NMR studies employing HMQC and HMBC spectra. Compound 1 was tested against a panel of multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA) strains and showed minimum inhibitory concentration values of 16 microg/ml.

Acremonium↗
PubMed1988

[In vitro activity of fusidic acid in combination with various antibiotics against Staphylococcus epidermidis].

In vitro antibacterial activity of fusidic acid (FUC) in combination with cefotaxime (CTX), imipenem (IMP), gentamicin (GEN), amikacin (AKN), rifampin (RIF), fosfomycin (FOS), vancomycin, pefloxacin (PEF) was studied against 19 presumably pathogen meti-R Staphylococcus epidermidis strains. The study was carried out by means of a microtiter checkerboard method (FICs index, 19 strains) and killing-curves (3 strains). FUC x GEN, FUC x AKN and FUC x IMP combinations were found synergistic with achievable therapeutic concentrations for IMP (MIC in the combination less than 1 microgram/ml) but with higher concentrations for AKN and GEN (greater than or equal to 8 micrograms/ml). FUC x PEF combinations were regularly antagonistic. FUC x RIF, and FUC x FOS combinations showed a modal FIC greater than or equal to 4 but were found respectively additive and synergistic with killing-curve method. Remaining FUC combinations results were variable. FUC resistant mutant frequency, studied for 3 S. epidermidis strains, was similar as S. aureus one's (0.5.10(-7) a 2.5.10(-8)).

Drug Resistance, Microbial↗
PubMed1980

Effects of cloxacillin, doxycycline, fusidic acid and lincomycin on mineralization and solubility of collagen in young rats.

The antibiotics doxycycline, fusidic acid and lincoymcin have recently been shown to reduce growth of bones and tensile strength of skin in young rats. Such adverse effects were not found in rats receiving cloxacillin. The present investigation deals with the influences of these four antibiotics on the mineralization of bones and on the solubility of collagen in skin. In rats receiving doxycycline the content of calcium and phosphorus in bones and the concentration of albumin in serum were reduced. None of the antibiotics had a detectable effect on the solubility of collagen.

Animals↗
PubMed1983

[Metabolic characteristics of a nystatin-resistant strain of a fungal producer of fusidic acid].

The physiological and morphofunctional properties of the polyene-sensitive and resistant mutants of fungus producing fusidic acid were studied comparatively. The highly active nystatin resistant mutant was characterized by the decreased growth rates, lowered sporulation levels, retarded synthesis of nucleic acids and protein, lower respiration activity and higher mycelium lipid contents. The ultrastructural investigation of the polyene-resistant strain revealed the presence of lower numbers of ribosomes, membrane structures and mitochondria. Destructive changes in mitochondria and lipid masses in the hyphal cytoplasm were also observed.

Aerobiosis↗
PubMed1992

Effect of fusidic acid on interleukin-1 (IL-1)- and IL-6-induced pancreatic beta-cell functions in rats.

Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs with a steroidal primary structure. Both compounds have been shown to prevent the lymphocyte co-stimulatory activities of the cytokines, interleukin (IL)-1 and IL-6, in a manner similar to that of cyclosporin A. As shown in this paper, fusidin also prevents the inhibitory effect of human recombinant IL-1 beta (rIL-1 beta) and the stimulatory effect of human rIL-6, on glucose-induced insulin production in vitro by normal rat pancreatic islets. The drug also inhibited rIL-1 beta-induced IL-6 production by the islets. Fusidin showed a dose-related effect at pharmacologically relevant concentrations from 3 to 30 micrograms/ml, and the drug was progressively less active when added 1, 4 and 24 h after rIL-1 beta. Electron microscopical studies showed that beta cells cultured for 72 h with rIL-1 beta accumulated less lipid in the presence of fusidin, most probably reflecting the functionally protective effect of the drug. Other characteristic ultrastructural changes induced in beta cells by rIL-1 beta were, however, not altered. It is suggested that fusidin may prove clinically effective as a modulator of IL-1- and IL-6-induced changes in beta-cell functions.

Animals↗
PubMed2002

Antidiabetogenic effect of fusidic acid in diabetes prone BB rats: a sex-dependent organ accumulation of the drug is seen.

Fusidic acid and its sodium salt (fusidin) are widely used antistaphylococcal drugs which possesses immunomodulatory properties. This prompted us to investigate whether high concentrations of fusidin could lower the diabetes incidence in diabetes-prone BB (BioBreeding) rats. As fusidin has previously been claimed to be poorly absorbed in rats after oral administration we wanted to measure the activity of the drug in various organs. Three groups of BB rats were used: 63 rats received fusidin dissolved in drinking water; 65 rats received chow containing fusidin; and 72 rats served as controls. The content of fusidin in the organs were examined microbiologically. The incidence of diabetes was significantly lower in the two fusidin-treated groups compared to the control group. The incidence was lower for male than for female rats in both experimental groups while no gender difference was seen in the control group. The female rats had a substantially higher content of fusidin in their organs than the males regardless of the administration way and regardless of diabetes outbreak or not. Interestingly, the fusidin treated non-diabetic rats displayed a lower random blood glucose level than the controls. In conclusion, fusidin is well absorbed after oral administration and it significantly reduces the diabetes incidence in BB rats. Fusidin accumulates substantially more in female rats which may be due to the steroid structure of fusidin. Whether the same phenomenon takes place in human beings is not known.

Administration, Oral↗
PubMed1998

Elimination of Staphylococcus intermedius in healthy dogs by topical treatment with fusidic acid.

Cutaneous and mucosal carriage of Staphylococcus intermedius was investigated in six healthy beagles before and after application of fusidic acid to mucosal surfaces as 1 per cent viscous eye drops twice daily for seven days. Bacterial populations were determined repeatedly over four weeks using quantitative techniques. The overall cutaneous populations of S intermedius reduced significantly (P < 0.001) two days after treatment but returned to pretreatment levels after a further week. The mucosal frequency of S intermedius reduced significantly (P < 0.01) two days after treatment and remained reduced (P < 0.01) at the end of the study. The mucosal populations were also reduced (P < 0.01) two days after treatment and remained lower (P < 0.05) after a further week. No such changes occurred in the control group of six beagles. The study indicates the importance of mucosae as carriage sites for S intermedius in dogs. This form of therapy may be useful as an additional tool against canine recurrent pyoderma.

Administration, Topical↗
PubMed2003

Tentative interpretative zone diameters for fusidic acid Neosensitabs on Mueller Hinton agar and three blood containing media.

Two hundred and ninety-two staphylococci were tested using fusidic acid Neosensitabs, a semiconfluent inoculum on Mueller Hinton agar and three blood containing agar media in order to investigate the interpretative zone diameters published by the manufacturer (Rosco). Zone diameters were, as expected, smaller on blood containing agar compared with Mueller Hinton agar. Many susceptible strains were intermediate on Danish Blood agar using the current breakpoints. We suggest that the interpretative zone diameters be changed to S>or=32, R or=24, R<or=22 on blood containing media.

Agar↗
PubMed1999

Fusidic acid in bone and joint infections.

The prominence of staphylococci as the causative agent in bone and joint infections suggests that fusidic acid (FA) has a potentially important role in their treatment. FA has been studied in a broad range of orthopaedic infections, mostly in combination with other antimicrobials. For susceptible organisms, particularly Staphylococcus aureus, it has demonstrable efficacy in acute osteomyelitis, chronic osteomyelitis, specialised forms of osteomyelitis such as calcaneal and vertebral infection, septic arthritis, prosthetic and other device-related infections. A small number of studies have also examined the use of FA alone for the treatment of bone infections, with evidence of good efficacy, as well as the local application of FA in plaster-of-Paris (POP) beads, or incorporated into bone cement, again with promising results. Further studies are required to confirm the efficacy of FA in the treatment of orthopaedic infections caused by methicillin-resistant strains of S. aureus.

Animals↗
PubMedDate not supplied

[Possible role of the respiratory system of Fusidium coccineum in regulating fusidic acid biosynthesis].

The respiration system was studied in three strains of the fungus Fusidium coccineum differing in their capability to synthesize fusidic acid. In all of the three strains, the system of oxidative phoshorylation predominated in supplying the cells with energy. In the strains with low and zero activities, the terminal oxidation of reduced equivalents occurred mainly via the respiration chain with cytochrome oxidase as a terminal component. In the strain with a high activity, there was an alternative cyanide resistant pathway, along with the classical cytochrome chain, and the complete switching to the alternative pathway coincided with the period of the antibiotic maximal accumulation. The induction of the alternative pathway in the strain with a high activity did not involve inhibition of the cytochrome region of the respiration chain. It was shown for the first time that the antibiotic synthesis and the character of cell differentiation can be changed by modifying the pathways of oxidation with specific inhibitors such as chloramphenicol and salicyl hydroxamate. Apparently, there is some general mechanism involved in regulating the production of the antibiotic, cell differentiation, and switching to the alternative oxidative pathway.

Energy Metabolism↗
PubMed1988

Effect of bile salts and of fusidic acid on HIV-1 infection of cultured cells.

Bile salts completely inactivated human immunodeficiency virus type 1 (HIV-1) in vitro and, unexpectedly, completely destroyed all the cultured persistently HIV-1 infected T cells. Fusidic acid, which likewise possesses the properties of an anionic surfactant, inactivated HIV-1 only at concentrations toxic to uninfected cultured cells. Bile salts or their derivatives, and other anionic surfactants, could be of therapeutic value in HIV-1 infections.

Acquired Immunodeficiency Syndrome↗
PubMed1983

[Ultrastructure of the spores of fungal strains, producers of fusidic acid, varying in antibiotic activity].

The nature of the fine structure of the spores of fusidic acid-producing organism changed with an increase in the antibiotic activity of its strains. Impairments in the structure of the cell coating were observed. The surface layers of the spore wall became labile, they were capable of separating, destructive impairment in the electron solid structures were detected in the spore cytoplasm, such impairments resulted in autolysis of extended areas. The lability of the surface layers of the spore wall promoted contacts between the spore cell coatings. The increased adhesive properties of the spore coatings resulted in formation of the spore "heads" typical of sporulation in highly active strains. The latter were characterized by a marked increase in the number of the spores filled with lipids and devoid of the main cell organelles and having a changed structure of the spore wall. This explained the marked decrease in the viability of the conidia of the highly active strains of the organism producing fusidic acid.

Anti-Bacterial Agents↗
PubMed2006

Interaction of fusidic acid with lipid membranes: Implications to the mechanism of antibiotic activity.

We have studied the effects of cholesterol and steroid-based antibiotic fusidic acid (FA) on the behavior of lipid bilayers using a variety of experimental techniques together with atomic-scale molecular dynamics simulations. Capillary electrophoretic measurements showed that FA was incorporated into fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes. Differential scanning calorimetry in turn showed that FA only slightly altered the thermodynamic properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers, whereas cholesterol abolished all endotherms when the mole fraction of cholesterol (X(chol)) was >0.20. Fluorescence spectroscopy was then used to further characterize the influence of these two steroids on DPPC large unilamellar vesicles. In the case of FA, our result strongly suggested that FA was organized into lateral microdomains with increased water penetration into the membrane. For cholesterol/DPPC mixtures, fluorescence spectroscopy results were compatible with the formation of the liquid-ordered phase. A comparison of FA and cholesterol-induced effects on DPPC bilayers through atomistic molecular dynamics simulations showed that both FA and cholesterol tend to order neighboring lipid chains. However, the ordering effect of FA was slightly weaker than that of cholesterol, and especially for deprotonated FA the difference was significant. Summarizing, our results show that FA is readily incorporated into the lipid bilayer where it is likely to be enriched into lateral microdomains. These domains could facilitate the association of elongation factor-G into lipid rafts in living bacteria, enhancing markedly the antibiotic efficacy of FA.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparison of silver sulfadiazine 1%, mupirocin 2%, and fusidic acid 2% for topical antibacterial effect in methicillin-resistant staphylococci-infected, full-skin thickness rat burn wounds.

Silver sulfadiazine 1%, mupirocin 2%, and fusidic acid 2% were compared to assess the antibacterial effect of a once-daily application on experimental rat 15% full-skin thickness burn wounds seeded 24 hours earlier with a 10 standard strain of methicillin-resistant staphylococci. The quantitative counts of seeded organism in burn eschar and subjacent muscle were determined at postburn day 7, beside the cultures of blood and lung biopsies. All tested topical agents were equally effective against methicillin-resistant in reducing local burn wound bacterial count and preventing systemic infection.

Administration, Topical↗
PubMed2007

An efficient new formulation of fusidic acid and betamethasone 17-valerate (fucicort lipid cream) for treatment of clinically infected atopic dermatitis.

To relieve the dryness of atopic dermatitis skin, a lipid formulation of fusidic acid and betamethasone 17-valerate (Fucicort Lipid cream) was developed as an additional treatment option to the established Fucicort cream. The two formulations were compared in patients with clinically infected atopic dermatitis. A total of 629 patients were randomized to twice daily double-blind treatment for 2 weeks with either Fucicort Lipid cream, Fucicort cream, or the new lipid cream vehicle. Clinical assessment was based on a Total Severity Score of the eczematous lesions. Bacteriological samples were taken at inclusion and at subsequent visit(s) if clinically infected lesions persisted. At the end of treatment, the mean reduction in Total Severity score was 82.9% in the lipid cream group, 82.7% in the cream group, and 33.0% in the vehicle group. The percentage of patients with a successful bacteriological response was 89.7%, 89.6% and 25.0%, respectively. Thus, the clinical and anti-bacterial effect of the lipid cream was found to be similar to that of the established cream formulation, and significantly better than that of the vehicle. The new lipid formulation, therefore, offers an efficient, safe and well-tolerated alternative for the short-term treatment of clinically infected atopic dermatitis.

Administration, Topical↗
PubMed1986

The use of fusidic acid gel in pilonidal abscess treatment: cure, recurrence and failure rates.

Eighty one consecutive patients with pilonidal abscesses were treated by incision, curettage and primary closure with local instillation of 2% fusidic acid gel (Fucidin Caviject). Normal activity was resumed early (mean 13 days) with a low recurrence rate (13%). The regimen allows treatment as an outpatient, healing time is short and there is an early return to work. These features provide potential financial benefits to the Health Service, employee and employer.

Abscess↗