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Effect of Bacteroides fragilis grown in the presence of clindamycin, metronidazole and fusidic acid on opsonization and killing of Escherichia coli.

Bactericidal action of human polymorphonuclear leucocytes on Escherichia coli in the presence of Bacteroides fragilis grown in subinhibitory concentrations of clindamycin, metronidazole and fusidic acid was studied. Bacteroides fragilis grown in the absence of drugs significantly inhibited the killing of Escherichia coli. Bacteroides fragilis grown in the presence of the drugs had a reduced inhibitory effect on the killing of Escherichia coli but this reduction was only significant for Bacteroides fragilis grown in 1/2 MIC of clindamycin. The phagocytosis of Bacteroides fragilis grown with and without clindamycin, as measured by killing, was the same. Complement consumption of Bacteroides fragilis grown with and without clindamycin did not differ. Clindamycin-treated Bacteroides fragilis fixed C3 to a significantly lower degree than did untreated bacteria. The chemiluminescence of Escherichia coli opsonized with serum preincubated with clindamycin-treated Bacteroides fragilis was significantly higher than with serum preincubated with untreated bacteria. These results suggested that in killing experiments of mixed Escherichia coli and Bacteroides fragilis, the mechanism underlying the reduced inhibitory capacity of clindamycin-exposed Bacteroides fragilis is related to greater availability of C3 in serum for opsonization of Escherichia coli.

Anti-Bacterial Agents↗

Fusidic acid plus betamethasone in infected or potentially infected eczema.

Eighty-one patients with atopic dermatitis and contact dermatitis received a 1-week treatment with 0.1% betamethasone alone on one side and 0.1% betamethasone plus 2% fusidic acid on the other side. Clinically, the combination was marginally superior and in patient preference a significant difference in favour of the combination was recorded. Bacteriologically, the combination eliminated 67% of bacteria originally present in the skin lesions compared with 51% with steroid alone.

Adolescent↗

In vitro activity of teicoplanin, vancomycin, A16686, clindamycin, erythromycin and fusidic acid against anaerobic bacteria.

The in vitro activity of teicoplanin and A16686, two new glycopeptide antibiotics was determined against 196 isolates of anaerobic bacteria. The activity of teicoplanin and A16686, in comparison with that of vancomycin, clindamycin, erythromycin and fusidic acid was 2 to 16 times higher against the gram positive anaerobes, namely, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Clostridium species, Peptococcus species and Peptostreptococcus species. However, Bacteroides fragilis was resistant to teicoplanin and A16686 while Bacteroides melaninogenicus and Bacteroides bivius were found to be sensitive.

Anti-Bacterial Agents↗

In-vitro activity of quinupristin/dalfopristin, levofloxacin and moxifloxacin against fusidic acid and rifampicin-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) from Malaysian hospitals.

The in-vitro susceptibility of quinupristin/dalfopristin, levofloxacin and moxifloxacin against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are also resistant to fusidic acid and rifampicin were carried out to determine whether these antibiotics can be used as an alternative treatment for multiply resistant MRSA strains. The minimum inhibitory concentrations (MIC) of these antibiotics were determined by E-test. Quinupristin/dalfopristin had good activity (MIC90 = 1 mg/L) against these strains while most of the strains showed intermediate resistance to moxifloxacin with MIC90 = 2 mg/L). However, more than 90% of these strains were resistant to levofloxacin with the MICs that ranged from 8 mg/L to 16 mg/L with the majority inhibited at 8 mg/L.

Anti-Bacterial Agents↗

Acute conjunctivitis. A comparison of fusidic acid viscous eye drops and chloramphenicol.

Fucidic acid viscous eye drops 1% given twice daily was compared with chloramphenicol eye drops 0.5% given 6 times daily in patients with acute conjunctivitis. Patients were recruited from 38 general practitioners in Norway. The mean duration of treatment was 6.6 days for Fucidic acid, 6.2 days for chloramphenicol. There was no major differences between the two groups in the bacteriological findings, and there was no significant difference in response to treatment. The use of fusidic acid in a carbomer vehicle as in Fucithalmic, has proved to give a long-lasting antibiotic concentration in the tear fluid, which allows the preferable twice daily application.

Acute Disease↗

EF-G-dependent GTPase on the ribosome. conformational change and fusidic acid inhibition.

Protein synthesis studies increasingly focus on delineating the nature of conformational changes occurring as the ribosome exerts its catalytic functions. Here, we use FRET to examine such changes during single-turnover EF-G-dependent GTPase on vacant ribosomes and to elucidate the mechanism by which fusidic acid (FA) inhibits multiple-turnover EF-G.GTPase. Our measurements focus on the distance between the G' region of EF-G and the N-terminal region of L11 (L11-NTD), located within the GTPase activation center of the ribosome. We demonstrate that single-turnover ribosome-dependent EF-G GTPase proceeds according to a kinetic scheme in which rapid G' to L11-NTD movement requires prior GTP hydrolysis and, via branching pathways, either precedes P(i) release (major pathway) or occurs simultaneously with it (minor pathway). Such movement retards P(i) release, with the result that P(i) release is essentially rate-determining in single-turnover GTPase. This is the most significant difference between the EF-G.GTPase activities of vacant and translocating ribosomes [Savelsbergh, A., Katunin, V. I., Mohr, D., Peske, F., Rodnina, M. V., and Wintermeyer, W. (2003) Mol. Cell 11, 1517-1523], which are otherwise quite similar. Both the G' to L11-NTD movement and P(i) release are strongly inhibited by thiostrepton but not by FA. Contrary to the standard view that FA permits only a single round of GTP hydrolysis [Bodley, J. W., Zieve, F. J., and Lin, L. (1970) J. Biol. Chem. 245, 5662-5667], we find that FA functions rather as a slow inhibitor of EF-G.GTPase, permitting a number of GTPase turnovers prior to complete inhibition while inducing a closer approach of EF-G to the GAC than is seen during normal turnover.

Cryoelectron Microscopy↗

In vitro susceptibility of methicillin-resistant Staphylococcus aureus and slime-producing and non-slime-producing coagulase-negative staphylococci to fusidic acid.

The in vitro susceptibility of 100 oxacillin-resistant Staphylococcus aureus and 100 oxacillin-resistant coagulase-negative staphylococci (CNS; 50 slime-negative and 50 slime-positive strains) was determined by agar dilution technique, with and without the addition of 50% human serum. All strains tested were highly sensitive to fusidic acid. S. aureus and CNS showed MIC50 values of 0.125 and 0.25 mg/l, respectively. MICs of all strains increased significantly in the presence of 50% human serum. Only minor differences were noted between the MICs of slime-producing and slime-deficient CNS.

Coagulase↗

Fusidic acid and insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) is a major cause of morbidity and mortality from long-standing complications. The autoimmune nature of IDDM has encouraged use of immunosuppressive and antiinflammatory strategies to better preserve residual pancreatic beta-cell function at the time of diagnosis. Fusidic acid and its sodium salt, fusidin, is a relatively atoxic antibiotic used mainly in the treatment of staphylococcal infections. Recently, fusidin has been demonstrated to possess immunosuppressive functions in vitro and in vivo, and the drug has shown promise in preventing the disease in animal models of IDDM and in a preliminary trial in IDDM patients.

Animals↗

Correlation of MIC methods and tentative interpretive criteria for disk diffusion susceptibility testing using NCCLS methodology for fusidic acid.

Three hundred and eight staphylococci and 43 Streptococcus pyogenes were tested by agar dilution, microbroth dilution, E-test, and disk diffusion using 5, 10 and 50 microg disks, as outlined by the NCCLS, in order to correlate the different MIC methods and to establish tentative species specific interpretive zone diameter breakpoints for fusidic acid. MIC results of the three methods were comparable. For Staphylococcus aureus, using MIC breakpoints of < or = 0.5 mg/L for susceptible and > or = 2 mg/L for resistant tentative interpretive zone diameters of > or = 20 mm and > or = 21 mm for susceptible and < or = 17 mm and < or = 18 mm for resistant are suggested for the 5 microg and the 10 microg disk, respectively. The 50 microg disk did not separate susceptible from resistant isolates. For streptococci a uniform MIC distribution of 2-8 mg/L was found.

Anti-Bacterial Agents↗

Inhibition of vacuolar H+-ATPases by fusidic acid and suramin.

The vacuolar system of eukaryotic cells is energized by a few ATP-driven ion pumps. One of these, the H+-ATPase, plays a major role in providing the protonmotive force for several organelles, as well as maintaining the proper pH inside the organelles. Formation of the protonmotive force in organelles isolated from the vacuolar system was inhibited by fusidic acid. The inhibition results from a combination of uncoupling the proton pumping and inhibition of the H+-ATPase activity. Suramin is also a potent inhibitor of the H+-ATPase from chromaffin granules. A possible connection between these activities and inhibition of HIV infection is pointed out.

Animals↗

Reduction of spontaneous autoimmune diabetes in diabetes-prone BB rats with the novel immunosuppressant fusidic acid. Effect on T-cell proliferation and production of interferon-gamma.

Diabetes-prone (DP) BB rats spontaneously develop a hyperglycaemic condition which closely resembles human insulin-dependent diabetes mellitus (IDDM), both in terms of clinical and histological features. The incidence of IDDM was significantly reduced when these animals were treated with 2 or 4 mg fusidic acid (FA)/day i.m. from day 30 to day 120 of age. In addition, the mean insulitis score was significantly diminished in the animals treated with FA compared to both vehicle-treated and untreated controls. Finally, 2 mg/day of FA i.m. prevented cell proliferation and interferon-gamma secretion from peripheral blood mononuclear cells upon ex vivo stimulation with concanavalin A. The capacity of FA to substantially reduce the incidence of autoimmune diabetes in a well-known animal model of human IDDM supports previous observations regarding the immunosuppressive properties of FA and its potential use in the treatment of human autoimmune diabetes.

Age Factors↗

In vitro susceptibility of penicillin-resistant Streptococcus pneumoniae to levofloxacin, selection of resistant mutants, and time-kill synergy studies of levofloxacin combined with vancomycin, teicoplanin, fusidic acid, and rifampin.

Among 180 clinical isolates of pneumococci, no strains were found to be resistant to levofloxacin (MIC, > or = 4 micrograms/ml) whereas 9% were resistant to ofloxacin and 7% were resistant to ciprofloxacin. Synergism was demonstrated by time-kill studies in nine of nine strains for the combination of levofloxacin and vancomycin and in six of nine strains for levofloxacin plus teicoplanin. The combinations of levofloxacin with rifampin or fusidic acid were indifferent. Resistant mutants could be selected using incremental concentrations of levofloxacin. For two of nine strains that were initially susceptible to levofloxacin, the MICs reached the resistance range (> or = 4 micrograms/ml). In contrast, ciprofloxacin and ofloxacin selected mutants from the susceptible to the resistant range more frequently (four of six and six of seven strains, respectively). These data argue for further study of levofloxacin against penicillin-resistant pneumococci.

Anti-Bacterial Agents↗

Sordarin inhibits fungal protein synthesis by blocking translocation differently to fusidic acid.

Sordarin derivatives are selective inhibitors of fungal protein synthesis, which specifically impair elongation factor 2 (EF-2) function. We have studied the effect of sordarin on the ribosome-dependent GTPase activity of EF-2 from Candida albicans in the absence of any other component of the translation system. The effect of sordarin turned out to be dependent both on the ratio of ribosomes to EF-2 and on the nature of the ribosomes. When the amount of EF-2 exceeded that of ribosomes sordarin inhibited the GTPase activity following an inverted bell-shaped dose-response curve, whereas when EF-2 and ribosomes were in equimolar concentrations sordarin yielded a typical sigmoidal dose-dependent inhibition. However, when ricin-treated ribosomes were used, sordarin stimulated the hydrolysis of GTP. These results were compared with those obtained with fusidic acid, showing that both drugs act in a different manner. All these data are consistent with sordarin blocking the elongation cycle at the initial steps of translocation, prior to GTP hydrolysis. In agreement with this conclusion, sordarin prevented the formation of peptidyl-[(3)H]puromycin on polysomes from Candida albicans.

Antifungal Agents↗

Efficacy of vancomycin, teicoplanin and fusidic acid as prophylactic agents in prevention of vascular graft infection: an experimental study in rat.

OBJECTIVES: To compare the efficacy of a single prophylactic dose of intra-peritoneal vancomycin and teicoplanin with anti-biotic treated Dacron grafts (vancomycin, teicoplanin, 10 or 40% fusidic acid-soaked grafts) in preventing vascular graft infections in a rat model. DESIGN: Prospective, randomized, controlled animal study. MATERIALS AND METHODS: The graft infections were established in the subcutaneous tissues of 80 female Sprague-Dawley rats by the implantation of Dacron prostheses followed by the topical inoculation with methicillin-resistant Staphylococcus aureus. The study groups were as follows: (1) uncontaminated control group, (2) untreated contaminated group, (3) contaminated group with intra-peritoneal vancomycin, (4) contaminated group with intra-peritoneal teicoplanin, (5) contaminated group received vancomycin-soaked Dacron graft, (6) contaminated group received teicoplanin-soaked Dacron graft, (7) contaminated group received 40% fusidic acid-soaked Dacron graft, and (8) contaminated group received 10% fusidic acid-soaked Dacron graft prophylaxis. The grafts were removed after 7 days and evaluated by a quantitative culture analysis. RESULTS: No infection was detected in controls. The untreated contaminated group had a high bacteria count (6.0 x 10(4) CFU/cm2 Dacron graft). Groups that received intra-peritoneal vancomycin or teicoplanin had less bacterial growth (4.8 x 10(3) and 3.9 x 10(3)CFU/cm2 Dacron graft, respectively). Similarly, the group that received 10% fusidic acid-soaked graft showed less bacterial growth (3.6 x 10(3) CFU/cm2 Dacron graft). The groups with vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts showed no evidence of infection. Statistical analyses demonstrated that intra-peritoneal prophylactic antibiotic treatment was less effective in inhibiting bacterial growth than high concentration antimicrobial-soaking of grafts. CONCLUSION: The use of vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts was effective in preventing primary prosthetic vascular graft infection.

Animals↗