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PubMed2004

A double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium difficile-associated diarrhoea.

OBJECTIVES: Few treatment options are currently available to treat patients suffering from an initial episode of Clostridium difficile-associated diarrhoea (CDAD). PATIENTS AND METHODS: A prospective, randomized controlled, double-blind trial was conducted to compare the efficacy of fusidic acid and metronidazole for treatment of patients experiencing a first episode of CDAD. The primary outcomes were clinical cure and clearance of C. difficile toxin determined on days 8-13, and secondary outcomes were clinical recurrence and reappearance of C. difficile toxin evaluated on days 35-40. RESULTS: Of the patients in the fusidic acid group, 83% were clinically cured in comparison to 93% in the metronidazole group (P=0.116) at the first follow-up visit. Clearance of C. difficile toxin did not differ between the two groups at that time. Clinical recurrence and reappearance of C. difficile toxin were noted in 27% and in 13% of the patients receiving fusidic acid, respectively and in 29% and 10% of those given metronidazole at the second follow-up on days 35-40. CONCLUSION: Since three of the four primary and secondary outcomes were almost identical for the two groups, the results indicate that fusidic acid is as effective as metronidazole in curing an initial episode of CDAD and can therefore be considered as an adequate alternative for treatment of this disease.

Anti-Bacterial Agents↗
PubMed1984

In vitro activities of teichomycin, fusidic acid, flucloxacillin, fosfomycin, and vancomycin against methicillin-resistant Staphylococcus aureus.

Flucloxacillin, fosfomycin, fusidic acid, teichomycin, and vancomycin were tested against 50 clinical isolates of methicillin-resistant Staphylococcus aureus by a broth macrodilution technique. Teichomycin had a narrow range of activity, similar to that of vancomycin (0.5 to 2.0 micrograms/ml). Fusidic acid had the lowest range of inhibitory activity, with 50 and 90% MICs of 0.19 and 0.35 micrograms/ml, respectively. Flucloxacillin and fosfomycin showed less activity, with MICs up to 32 micrograms/ml.

Anti-Bacterial Agents↗
PubMed2002

[Increase in rate of resistance to fusidic acid among Staphylococcus aureus isolates from patients admitted with atopic dermatitis].

To determine whether there has been an increase in the incidence of resistance to fusidic acid among Staphylococcus aureus isolates in the Netherlands, a retrospective study was carried out. The resistance pattern of S. aureus isolates from patients with atopic dermatitis at the Dermatology inpatient department of the University Medical Centre Utrecht was determined during the period 1995-2001. The rate of resistance increased from 9.7% to 23.4% during this period, whereas the rate of resistance of S. aureus to methicillin remained stable at around 0.5%. Prolonged topical use of fusidic acid is probably the main cause for the increase in fusidin resistance. Therefore it is advised to limit the use of fusidic acid for infected dermatitis to short periods of about two weeks, and only after sensitivity of the strain to fusidin has been confirmed.

Anti-Bacterial Agents↗
PubMed1992

Fusidic acid is highly active against extracellular and intracellular Mycobacterium leprae.

The activity of fusidic acid against Mycobacterium leprae was studied in axenic medium and in bacilli residing within mouse peritoneal macrophages. Activity was assessed by subsequent quantitation of bacillary radiorespirometric activity. Significant inhibition in both systems was observed at 0.156 micrograms/ml, and an approximately 50% reduction in activity occurred after exposure to 1.25 to 2.5 micrograms/ml. The excellent human pharmacokinetics and in vitro activity of fusidic acid against the leprosy bacillus warrant a clinical trial of this drug for leprosy.

Animals↗
PubMed2004

Fusidic acid resistance in Staphylococcus aureus.

This review summarises current knowledge of the microbiological and clinical aspects of fusidic acid resistance in Staphylococcus aureus, and makes recommendations about fusidic acid prescribing and further research.

Anti-Bacterial Agents↗
PubMed2000

Fusidic acid disk diffusion testing of clostridium difficile can be calibrated using single-strain regression analysis.

Single-strain regression analysis (SRA) was employed to calibrate the disk diffusion antibiotic susceptibility test for fusidic acid and Clostridium difficile. MIC determinations of 40 clinical isolates of C. difficile were performed with the E-test. The disk diffusion test was standardized according to the Swedish Reference Group for Antibiotics (SRGA). Disks used for SRA contained 1.5, 5, 15, 50 and 150 microg fusidic acid and the routine disk contained 50 microg fusidic acid. A control strain, ATCC 9689, was also tested. SRA constants A and B of the regression lines were calculated. This permitted the determination of zone breakpoints for C. difficile. When applying the pharmacological MIC S and R limits set by SRGA to the E-test results I strain of C. difficile was interpreted as resistant. Zone breakpoints corresponding to the pharmacological MIC limits and calculated using the mean SRA constants for the 40 clinical isolates lead to all strains being interpreted as susceptible. SRA calculations enable laboratories to set up calibrated disk tests with species-related and laboratory-specific interpretations.

Anti-Bacterial Agents↗
PubMed2006

Fusidic acid viscous eyedrops--an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK optometrists.

Recent changes in UK law have allowed UK-based optometrists to sell and supply fusidic acid viscous eyedrops, providing it is in the course of their professional activity and in an emergency. Alternatively, the optometrist may access fusidic acid viscous eyedrops, for a named patient, using a written order supplied to a pharmacy. This review provides details of the legal background to these changes, examines the common causes of a bacterial conjunctivitis, examines the mechanism of action of this narrow spectrum antibiotic as a bacteriostatic agent, reviews the susceptibility of common ocular isolates of bacteria to the drug and presents details of the expected pharmacokinetics of the viscous eyedrops. From this perspective, a systematic review is provided of the clinical studies which have investigated the use of fusidic acid viscous eyedrops and their outcome. The indicated use is generally for the treatment of bacterial conjunctivitis and/or blepharoconjunctivitis, especially that caused by Staphylococcus, but not Streptococcus or Haemophilus sp. (more likely associated with concurrent nasopharyngeal infections). The usual regimen for use is twice daily for 5-10 days, depending on severity, and can initially be used more intensively (four times per day). It may also be used for the management of corneal and conjunctival abrasions and foreign body injuries, or some cases of chronic blepharitis.

Administration, Topical↗
PubMed1995

Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea.

A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy.

Blepharitis↗
PubMed1990

Effect of fusidic acid on migration and chemiluminescence of polymorphonuclear leukocytes.

Incubation of polymorphonuclear leukocytes (PMNs) in fusidic acid resulted in a decrease of random migration and chemiluminescence. The effects were dose-dependent but moderate, with statistical significance only at concentrations of 50 mg/l or more. At concentrations used for therapy of bacterial infections and AIDS, fusidic acid was not shown to be deleterious to these aspects of PMN function.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Antibacterial antagonism between fusidic acid and ciprofloxacin.

A routine laboratory disk susceptibility testing of a resistant Staphylococcus aureus strain showed that around the ciprofloxacin disk, placed by chance in proximity to a fusidic acid disk, the inhibition zone was truncated. Follow-up of this observation by a planned disk approximation method showed that there is a real antagonism between these two antibacterial agents. The antagonism was observed while testing S. aureus isolates including the standard ATCC 25923 strain, with Bacillus subtilis ATCC 6633 spores and also with a mutant Escherichia coli made fusidic acid susceptible. The antagonistic property was found structure-specific, only associated with those fluoroquinolones containing the cyclopropyl substituent at the N1-position: ciprofloxacin, enrofloxacin, sparfloxacin and WIN 57273. Fluoroquinolones without this substituent such as enoxacin, norfloxacin, pefloxacin and ofloxacin were not antagonized by fusidic acid, the steroidal Gram-positive active antibiotic.

Anti-Infective Agents↗
PubMed2002

Molecular fingerprinting of fusidic acid- and rifampicin-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) from Malaysian hospitals.

The emergence and spread of multiresistant methicillin-resistant Staphylococcus aureus (MRSA) strains, especially those resistant to fusidic acid and rifampicin, in Malaysian hospitals is of concern. In this study DNA fingerprinting by PFGE was performed on fusidic acid- and rifampicin-resistant isolates from Malaysian hospitals to determine the genetic relatedness of these isolates and their relationship with the endemic MRSA strains. In all, 32 of 640 MRSA isolates from 9 Malaysian hospitals were resistant to fusidic acid and rifampicin. Seven PFGE types (A, ZC, ZI, ZJ, ZK, ZL and ZM) were observed. The commonest type was type ZC, seen in 72% of isolates followed by type A, seen in 13%. Each of the other types (ZI, ZJ, ZK, ZL and ZM) was observed in a single isolate. Each type, even the commonest, was found in only one hospital. This suggests that the resistant strains had arisen from individual MRSA strains in each hospital and not as a result of the transmission of a common clone.

Anti-Bacterial Agents↗
PubMed1997

The postantibiotic effect of fusidic acid against gram-positive bacteria.

The in-vitro postantibiotic effect (PAE) of fusidic acid was tested for six strains of Staphylococcus aureus and four strains of Streptococcus pyogenes. The maximum PAE that could be achieved was more than 3 h, but at concentrations of antibiotic attainable in humans, the PAE was less than 2 h. Additional experiments were performed in albumin, to examine the effect of the strong protein binding of fusidic acid on the MIC and PAE. MICs were increased, but at the same multiple of the MIC, PAEs were similar to those performed in Mueller-Hinton broth.

Fusidic Acid↗
PubMed1999

Fusidic acid non-antibacterial activity.

In 1978 the first report was published indicating that fusidic acid had an immunomodulatory effect. This study describing an in vitro effect on white cells was followed by an in vivo study showing improved survival in heart transplanted mice. In 1990 these immunomodulatory effects were shown to be related to suppression of cytokine production in animal models of septic shock and insulin dependent diabetes. Disease modulation has been investigated in a number of immunologically mediated diseases, HIV infection, Behcet's disease, Crohn's disease, uveitis and scleroderma. However whether fusidic acid has any useful function as an immunomodulating agent has yet to be fully explored.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Fusidic acid suspension twice daily: a new treatment schedule for skin and soft tissue infection in children, with improved tolerability.

OBJECTIVE: This multicentre, randomized, double-blind, parallel group study aimed to compare a new regimen of fusidic acid suspension against a standard regimen in children with skin and soft tissue infections. METHODS: Treatment groups were given either a new regimen of fusidic acid suspension (20 mg/kg divided b.i.d.) or a standard regimen (50 mg/kg divided t.i.d.), which were administered for 5 days in both groups and for a further 5 days if evidence of infection persisted. Assessment of those cured was carried out 14 days. RESULTS: Both regimens were effective. Cure was achieved in 194 (91.1%) of the 213 children given the new b.i.d. dosage and for 194 (89.4%) of the 217 children given the standard t.i.d. dosage (intention-to-treat population; p=0.72). Cure was maintained at the follow-up assessment for 94.8% (181 of 191) and 95.7% (180 of 188), respectively, of the children. Bacteriological cure of infections due to fusidic acid susceptible Staphylococcus aureus and/or group A beta-haemolytic streptococci, with elimination of pathogens, was achieved in all 121 (100%) children treated with the new b.i.d. regimen and in 123 (99.2%) of the 124 children treated with the standard TID regimen. CONCLUSION: The new twice-daily regimen had significantly better tolerance (p=0.025).

Administration, Oral↗
PubMed1966

Naturally-occurring fusidic acid resistance in staphylococci and its linkage to other resistances.

Although Staph. aureus resistant to fusidic acid can be selected in vitro and has been found in vivo following treatment, naturally occurring strains without previous exposure to the drug have not, so far, been reported. Four such strains were isolated in the area of the North West Surrey Group Laboratory between August and September 1965, and six at Hammersmith Hospital during the first four months of 1966. In two of these resistance to fusidic acid was very unstable and its loss was accompanied by loss of resistance to penicillin in the first and to tetracycline and kanamycin in the second, although this strain remained resistant to penicillin.

Drug Resistance, Microbial↗
PubMed1999

In vitro percutaneous absorption of fusidic acid and betamethasone 17-valerate across canine skin.

The penetration of betamethasone 17-valerate and fusidic acid through dog skin was measured in vitro. In order to detect the small amounts of diffused compounds, a liquid chromatography-mass spectrometric method was developed with sensitivity limits for both compounds of 5 ng/ml. After application to the skin surface of a topical gel preparation containing these compounds at the anticipated therapeutic dose rate, about 10 per cent of the betamethasone 17-valerate penetrated the skin over a 24-hour period, with no significant metabolism of the ester. About 1.3 per cent of the applied dose of fusidic acid was similarly recovered. The results demonstrated rapid penetration of both compounds through the epidermis.

Administration, Cutaneous↗
PubMedDate not supplied

Intraocular penetration of fusidic acid with topical Fucithalmic.

Fucithalmic is a newly developed 1% microcrystalline suspension of the antistaphylococcal antibiotic fusidic acid. Penetration into the eye was investigated in twenty patients about to undergo cataract extraction. A single dose produced median antibiotic levels in the aqueous humour of 0.3 mcg/ml, maintained for at least 12 hours. Repeated doses produced significantly higher levels, median 0.8 mcg/ml, indicating some cumulative effect. The results show that fusidic acid passes the corneal aqueous barrier, and twice daily administration of Fucithalmic gives aqueous concentrations comparable with or higher than those seen after recommended systemic administration.

Aqueous Humor↗
PubMed2005

Structural insights into fusidic acid resistance and sensitivity in EF-G.

Fusidic acid (FA) is a steroid antibiotic commonly used against Gram positive bacterial infections. It inhibits protein synthesis by stalling elongation factor G (EF-G) on the ribosome after translocation. A significant number of the mutations conferring strong FA resistance have been mapped at the interfaces between domains G, III and V of EF-G. However, direct information on how such mutations affect the structure has hitherto not been available. Here we present the crystal structures of two mutants of Thermus thermophilus EF-G, G16V and T84A, which exhibit FA hypersensitivity and resistance in vitro, respectively. These mutants also have higher and lower affinity for GTP respectively than wild-type EF-G. The mutations cause significant conformational changes in the switch II loop that have opposite effects on the position of a key residue, Phe90, which undergoes large conformational changes. This correlates with the importance of Phe90 in FA sensitivity reported in previous studies. These structures substantiate the importance of the domain G/domain III/domain V interfaces as a key component of the FA binding site. The mutations also cause subtle changes in the environment of the "P-loop lysine", Lys25. This led us to examine the conformation of the equivalent residue in all structures of translational GTPases, which revealed that EF-G and eEF2 form a group separate from the others and suggested that the role of Lys25 may be different in the two groups.

Crystallography, X-Ray↗