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PubMed2005

Comparative study of prednisolone alone and prednisolone plus fusidic acid in the treatment of children with steroid-responsive nephrotic syndrome.

BACKGROUND: There are several reports in the literature indicating that fusidic acid owns functions similar to those of cyclosporin. As cyclosporin has effectively been used in frequently relapsing steroid-responsive nephrotic syndrome we carried out this study to determine whether fusidic acid used along with prednisolone diminishes rate of steroid-responsive nephrotic syndrome relapses in children. PATIENTS AND METHODS: The patients were randomly allocated to receive either prednisolone alone or prednisolone plus fusidic acid for two months in standard doses. In the cases of relapses the treatment was changed to the comparative treatment method. Altogether 18 children (12 boys and 6 girls) aged 1.3 to 13.2 years entered the study. Thirteen of them were treated by either method on different occasions, four patients were treated with prednisolone only, and one child was treated with prednisolone plus fusidic acid only. Thus, there were 17 evaluable treatment courses with prednisolone alone and 14 courses with prednisolone plus fusidic acid. The patients were followed-up as long as the remission lasted. RESULTS: There was prompt and complete response under the influence of both treatment methods. However, relapses occurred in all the patients irrespective of the mode of treatment. Mean duration of remissions did not differ significantly between the study groups (17.8+/-20.4 weeks in the prednisolone group and 18.3+/-23.9 weeks in the prednisolone plus fusidic acid group; p>0.05). There were no statistically significant differences in laboratory parameters reflecting therapeutic efficacy in the comparative treatment groups, too. CONCLUSION: Thus, it was not revealed any remission-sustaining efficacy of fusidic acid used in standard doses for two months along with prednisolone in children with frequently relapsing steroid-responsive nephrotic syndrome.

Adolescent↗
PubMed2000

MIC determination of fusidic acid and of ciprofloxacin using multidisk diffusion tests.

OBJECTIVE: To investigate the possibility of estimating the MICs of fusidic acid and ciprofloxacin for bacterial isolates using series of antibiotic disk concentrations in diffusion tests, so-called M-tests. METHODS: Thirty Staphylococcus aureus and S. epidermidis strains were tested for fusidic acid susceptibility. Sixty-one clinical isolates of eight bacterial species were tested for ciprofloxacin susceptibility. Disk diffusion was standardized according to the Swedish reference group for antibiotics (SRGA). For fusidic acid, a series of disks (1.5, 5.0, 15, 50 and 150 microg) was used. Ciprofloxacin was applied in four different diffusion sources (1, 3, 10 and 30 microg) on a single strip, the M-strip, and used. True MIC values were determined using the standardized agar dilution method according to the SRGA. Single-strain regression analysis (SRA) was employed to calculate critical concentration equivalents (Qzero). RESULTS: Fusidic acid and ciprofloxacin critical concentrations were determined for the bacterial isolates. The mean conversion factors for Qzero to yield the true MIC were 2.06 (range 0.34-8.9) for fusidic acid and 2.05 (range 0.37-8.1) for ciprofloxacin. There was a correlation between true MIC values (all MICs expressed as 2 log + 9) and the calculated MIC values (Qzero x conversion factor) for both fusidic acid (R = 0.9822) and ciprofloxacin (R = 0.9696). CONCLUSIONS: MIC values of clinical isolates can be estimated using SRA calculations on zone measurements in disk tests with several concentrations of the antibiotic in diffusion sources.

Anti-Bacterial Agents↗
PubMed1998

The effect of dicloxacillin and fusidic acid on the extracellular and intracellular killing of Staphylococcus aureus.

The effect of dicloxacillin and fusidic acid used alone and in combination on the extracellular and intracellular killing of four isolates of Staphylococcus aureus in the presence of serum was studied. At the extracellular level, dicloxacillin (8 mg/L) had a bactericidal effect on all four isolates, whereas fusidic acid (64 mg/L) had a bacteriostatic effect on two isolates and no effect on the two other isolates. Fusidic acid significantly inhibited the extracellular bactericidal effect of dicloxacillin on two isolates. Intracellular killing was measured in human neutrophil granulocytes. Dicloxacillin (8 mg/L) significantly increased the intracellular killing of all four isolates, while fusidic acid (64 mg/L) significantly increased the intracellular killing of three isolates, but the killing was significantly lower than that of dicloxacillin. When the antibiotics were combined the intracellular killing of three of the isolates was significantly lower than that of dicloxacillin alone. The viability of the granulocytes and their ability to produce superoxide anion were not affected by the antibiotics. In conclusion, we found that the increased intracellular killing of S. aureus by dicloxacillin was inhibited by fusidic acid.

Adult↗
PubMed1997

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis.

Fusidic acid is metabolized and excreted by the liver. It is generally assumed that renal impairment has no effect on serum concentrations. However, there are few data on the pharmacokinetics of fusidic acid in patients with chronic renal failure, particularly in those requiring dialysis. Seven patients with chronic renal failure on haemodialysis were given 500 mg sodium fusidate orally every 8 h for the 48 h between dialysis. Seven patients on continuous ambulatory peritoneal dialysis (CAPD) were given the same dosage regimen for seven doses. Fusidic acid concentrations were measured by HPLC. Accumulation was seen, and in 12 of the 14 patients steady-state pharmacokinetics had not been achieved by the third day. In haemodialysis patients, mean (range) Cmax values for the first dose were 13.0 (2.0-25.5) mg/L and for the sixth dose were 40.5 (10.1-69.9) mg/L. Serum concentrations were not reduced by haemodialysis. In CAPD patients mean Cmax values for the first dose were 16.0 (4.8-33.8) mg/L and for the seventh dose were 33.9 (23.4-61.9) mg/L. Fusidic acid concentrations of 1.0-2.3 mg/L were detected in peritoneal dialysis fluid in six of the seven CAPD patients. In both patient groups there was a tendency towards increased T(1/2) with repeated dosing. Protein-binding of fusidic acid in patient serum samples was 87.6-94.6%.

Adult↗
PubMed1999

Susceptibility testing and clinical effect of fusidic acid in oxacillin-resistant Staphylococcus aureus infections.

One hundred and six oxacillin-resistant Staphylococcus aureus (ORSA) isolates collected from various clinical specimens at Mackay Memorial Hospital during the period from 1997 to 1998 were tested. The MICs of fusidic acid against ORSA isolates were in the range of 0.06 microgram/mL to 4 micrograms/mL. There was only one ORSA isolate (0.9%) resistant to fusidic acid in this study. Twenty-four patients with ORSA infection were enrolled into the study between July 1997 to June 1998. Four patients without the evidence of sepsis received oral fusidic acid only. The other 20 patients with sepsis received intravenous glycopeptide first, and then the oral fusidic acid for 7 to 10 days. Oral fusidic acid was used for mild ORSA infection and achieved satisfactory clinical outcome. In severe ORSA infection, it was found that sequential therapy with fusidic acid had relapsed in three patients. We concluded that oral fusidic acid achieved a satisfactory outcome in our patients with mild ORSA infection. In such cases, fusidic acid may provide an effective alternative treatment of choice. The rare side effect of granulocytopenia and jaundice was noted in our case series. The side effect may be not so rare as previously thought, if it had been carefully looked for.

Adult↗
PubMed1995

An in vitro study of fusidic acid susceptibility amongst isolates from conjunctival swabs.

The aim of this study was to examine the in vitro activity of fusidic acid against bacterial isolates from conjunctival swabs. Conjunctival swabs from 213 patients with conjunctivitis were examined. One or more pathogens were grown from 73 patients. Forty per cent of isolates were resistant to fusidic acid on disc sensitivity testing. Reduced sensitivity was detected by minimum inhibitory concentration testing in many isolates of H. influenzae and an isolate of S. pneumoniae. In addition, the in vitro activity of fusidic acid was determined against upper respiratory tract isolates of H. influenzae, S. pneumoniae and M. catarrhalis; this showed that many isolates had a reduced sensitivity to fusidic acid. Topical fusidic acid may not be optimal empiric therapy of bacterial conjunctivitis.

Anti-Bacterial Agents↗
PubMed2001

[Superficial pyoderma requiring oral antibiotic therapy: fusidic acid versus pristinamycin]].

OBJECTIVE: This study was aimed to compare the clinical and antibacterial efficacy of fusidic acid 500 mg twice a day, per os, over 7.5 days) to pristinamycin 1 g twice a day, per os, over 10 days). METHODS: Patients aged over 18, suffering from a superficial pyoderma requiring antibiotherapy and having given their informed consent were enrolled in a controlled, multicentre, double blind double dummy, parallel groups study. From day 0 to day 10, the patients received the randomised treatment. Those who were cured at day 11 had a visit at day 25 without any treatment between day 11 and day 25. A swab was performed on days 0, 11 and 25. The two treatment groups were compared in terms of efficacy, safety and global cost. RESULTS: 334 patients seen in dermatologic consultation were included in the study. 313 patients were analysed on an intent-to-treat basis. 158 received fusidic acid (FA) and 155 were treated with pristinamycin (P). At D11, 126 patients were cured in the FA group (79.7%) and 118 in the P group (76.1%) (p = 0.44). The bacteriological success rate was 85.2% in the FA group and 82.7 in the P group (p = 0.67). The recovery was confirmed in 92.6% of the FA patients and 90.4% of the P patients at D25 (p = 0.56). Digestive tolerance was better with fusidic acid than with pristinamycin. In economic terms, fusidic acid was cheaper than pristinamycin: 443 French francs in the FA group versus 545 FF in the P group. CONCLUSION: Therefore we conclude that an oral course of 7.5 days with fusidic acid is an efficient and cheaper alternative to a treatment with pristinamycin over 10 days.

Administration, Oral↗
PubMed1994

In-vitro antibacterial activity of fusidic acid alone and in combination with other antibiotics against methicillin-sensitive and -resistant Staphylococcus aureus.

The activity of fusidic acid alone and in combination with gentamicin, oxacillin, rifampicin, fosfomycin and ciprofloxacin was investigated against 36 strains of Staphylococcus aureus. The fusidic acid MIC50 of 0.06 mg/L and MIC90 of 0.125 mg/L were determined for 36 strains. Bactericidal activity of fusidic acid was confirmed. Several types of interaction were observed with other antibiotics: dominant effect of fusidic acid over gentamicin; synergy with rifampicin for three or four strains; indifference or dominance with oxacillin, indifference with vancomycin, indifference or dominance with fosfomycin, and indifference with ciprofloxacin. Antagonism was seen with only one strain, following exposure to fusidic acid and rifampicin.

Ciprofloxacin↗
PubMed2001

Synthesis and conformational analysis of fusidic acid side chain derivatives in relation to antibacterial activity.

Novel fusidic acid type antibiotics having flexible side chains are described. Saturation of the double bond between C-17 and C-20 of fusidic acid produces four stereoisomers differing in the configuration at C-17 and C-20. The structure-activity relationship of the stereoisomers was studied using computer-assisted analyses of low-energy conformations and crystallographic data. Only one of the four stereoisomers showed potent antibiotic activity comparable with that of fusidic acid, whereas the other three stereoisomers retained little or no activity. The orientation of the side chain is crucial, and there is only a limited space for bioactive side chain conformations. This investigation demonstrates the essential role of the side chain conformations in relation to antibacterial activity and contradicts earlier assumptions that the Delta17(20) bond is an essential feature in the molecule.

Anti-Bacterial Agents↗
PubMed1995

Antimicrobial activity of fusidic acid and disk diffusion susceptibility testing criteria for gram-positive cocci.

The in vitro activity of fusidic acid was assessed and was compared with those of cloxacillin, cefamandole, vancomycin, teicoplanin, ofloxacin, ciprofloxacin, pefloxacin, and fleroxacin against 500 gram-positive cocci: 151 Staphylococcus aureus, 197 coagulase-negative staphylococci, and 152 Enterococcus faecalis strains. All clinical isolates were concomitantly tested by disk diffusion and agar dilution procedures as outlined by the National Committee for Clinical Laboratory Standards. The results with fusidic acid were further analyzed by regression line and error rate-bounded methods. With control American Type Culture Collection organisms, the values were within the limits of the National Committee for Clinical Laboratory Standards or published limits. The incidence of resistance to fusidic acid was 0.7% for S. aureus, 2.5% for coagulase-negative staphylococci, and 99.3% for E. faecalis. The correlation coefficient between the results of disk diffusion and agar dilution tests with fusidic acid was 0.90. Current interpretive criteria for susceptibility to fusidic acid (i.e., MIC of < 2 micrograms/ml and inhibitory zone of 20 mm) gave 1% false susceptibility (all strains being E. faecalis). This error rate is practically eliminated if a zone diameter of 21 mm is considered the breakpoint for susceptibility.

Drug Resistance, Microbial↗
PubMedDate not supplied

Pharmacokinetic investigation of fusidic acid 1% viscous eye drops in healthy volunteers.

The biological half-life of fusidic acid was measured in tear fluid samples from the inferior fornix of 14 healthy volunteers after instillation of one drop of viscous fusidic acid eye drops. The study comprised four test days separated by six days of wash-out. On the first test day the concentrations of fusidic acid were measured 1 h after installation, on the second test day 3 h after, on the third test day 6 h after, and on the last day 12 h after instillation. The median fusidic acid concentrations in the tear fluid were 15.7 micrograms/ml, 15.2 micrograms/ml, 10.5 micrograms/ml and 5.6 micrograms/ml on the four days. This corresponds to a biological half-life of 7.3 h. Some of the volunteers reported mild local discomfort lasting a few minutes.

Administration, Topical↗
PubMed1971

Interaction of albumin and fusidic acid.

1. By combining the agar plate diffusion technique for determination of antibiotic activity and zone microelectrophoresis in agar gel, the activity of fusidic acid in individual serum proteins of blood and pus obtained from patients given sodium fusidate revealed albumin to be responsible for the protein binding of this antibiotic.2. Based on the assumption that only free fusidic acid is microbiologically active, the relationship between the concentration of albumin and the ratio of free to total fusidic acid was determined at four concentrations of free fusidic acid, using as test organisms four differently sensitive variants of a Staphylococcus aureus strain. At each concentration an increasing amount of albumin (0-40 mg/ml culture medium) decreased the activity of fusidic acid as determined in serial dilutions (IC50).3. The law of mass action expressed as Langmuir's adsorption isotherm was valid if a correction for the influence of albumin on the sensitivity of the strain of Staph. aureus was introduced. For other test organisms no correction is necessary. The constant in Langmuir's adsorption isotherm was K=78400+/-8200 l./mol and n=3.15 (95% confidence limits: 2.09-5.52).4. The mean blood concentration was 20.8 mug/ml and the mean pus concentration 17.2 mug/ml in nineteen sets of blood and pus samples. The ratio of pus to blood corresponds to the ratio of published values for the protein concentrations in serum and in inflammatory oedema.5. It is concluded that for albumin bound drugs the ;storage depot' of the organism also includes the fluid of the tissue spaces including the inflammatory oedema. As recent studies have revealed an extravascular albumin pool similar in size to the plasma pool, this ;storage depot' should not be neglected.

Agar↗
PubMed2004

Survey, characterization and susceptibility to fusidic acid of Staphylococcus aureus in the Carmarthen area.

OBJECTIVE: This retrospective study was designed to investigate the possible reasons for an apparent increase in fusidic acid resistance among Staphylococcus aureus. MATERIALS AND METHODS: The Datastore records of the Communicable Disease Surveillance Centre, Wales, UK were reviewed in conjunction with information concerning the prescribing of fusidic acid. RESULTS: During the 5 year study period (1997-2001), a rise in the incidence of fusidic acid resistance was noted, particularly among paediatric patients presenting with infected eczema and impetigo, which may be related to the observed increase in prescriptions of topical fusidic acid. Extended phenotypic and genotypic characterization of a limited number (n=31) of isolates from 2002 showed that fusidic acid-resistant strains of S. aureus were typically from patients with impetigo and isolates fell into a single clonal group. Conversely, isolates from other skin disease (eczema, dermatitis and abscesses) were usually susceptible to fusidic acid and proved a diverse group. CONCLUSION: This study provides valuable data on the prevalence of fusidic acid-resistant S. aureus, the genetic background of the strains, and their association with clinical disease in both the healthcare environment and community setting in the catchment area served by the Laboratory.

Adolescent↗
PubMed1983

Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. A plasmid-encoded mechanism involving antibiotic binding.

Plasmid-encoded fusidic acid resistance in Escherichia coli is mediated by a common variant of chloramphenicol acetyltransferase (EC 2.3.1.28), an enzyme which is an effector of chloramphenicol resistance. Resistance to chloramphenicol is a consequence of acetylation of the antibiotic catalysed by the enzyme and the failure of the 3-acetoxy product to bind to bacterial ribosomes. Cell-free coupled transcription and translation studies are in agreement with genetic studies which indicated that the entire structural gene for the type I chloramphenicol acetyltransferase is necessary for the fusidic acid resistance phenotype. The mechanism of resistance does not involve covalent modification of the antibiotic. The other naturally occurring enterobacterial chloramphenicol acetyltransferase variants (types II and III) do not cause fusidic acid resistance. Steady-state kinetic studies with the type I enzyme have shown that the binding of fusidic acid is competitive with respect to chloramphenicol. The inhibition of polypeptide chain elongation in vitro which is observed in the presence of fusidic acid is relieved by addition of purified chloramphenicol acetyltransferase, and equilibrium dialysis experiments with [3H]fusidate and the type I enzyme have defined the stoichiometry and apparent affinity of fusidate for the type I enzyme. Further binding studies with fusidate analogues, including bile salts, have shown some of the structural constraints on the steroidal skeleton of the ligand which are necessary for binding to the enzyme. Determinations of antibiotic resistance levels and estimates of intracellular chloramphenicol acetyltransferase concentrations in vivo support the data from experiments in vitro to give a coherent mechanism for fusidic acid resistance based on reversible binding of the antibiotic to the enzyme.

Acetyltransferases↗
PubMed1990

Fusidic acid in staphylococcal bone and joint infection.

Over 25 years experience with fusidic acid in the treatment of bone and joint infections is reviewed. Fusidic acid, usually given concurrently with another antibiotic, has proved effective in a wide variety of staphylococcal infections, including acute osteomyelitis and septic arthritis. It is a valuable adjunct to surgery in patients with chronic osteomyelitis. Oral therapy is generally well tolerated, apart from gastrointestinal side effects in a small proportion of cases. Use of fusidic acid in other orthopaedic situations is considered in the light of recent information.

Bone Diseases↗
PubMed2002

Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial.

OBJECTIVE: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. DESIGN: Randomised placebo controlled trial. SETTING: General practices in Greater Rotterdam. PARTICIPANTS: 184 children aged 0-12 years with impetigo. MAIN OUTCOME MEASURES: Clinical cure and bacterial cure after one week. RESULTS: After one week of treatment 55% of the patients in the fusidic acid group were clinically cured compared with 13% in the placebo group (odds ratio 12.6, 95% confidence interval 5.0 to 31.5, number needed to treat 2.3). After two weeks and four weeks the differences in cure rates between the two groups had become smaller. More children in the placebo group were non-compliant (12 v 5) and received extra antibiotic treatment (11 v 3), and more children in the placebo group reported adverse effects (19 v 7). Staphylococcus aureus was found in 96% of the positive cultures; no strains were resistant to fusidic acid. CONCLUSIONS: Fusidic acid is much more effective than placebo (when both are given in combination with povidone-iodine shampoo) in the treatment of impetigo. Because of the low rate of cure and high rate of adverse events in the placebo group, the value of povidone-iodine in impetigo can be questioned.

Anti-Bacterial Agents↗
PubMed2002

Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101.

We report the cloning of the fusidic acid and cadmium resistance determinants from Staphylococcus aureus plasmid pUB101. The pUB101 fusidic acid resistance determinant was located on a 2.9 kb HindIII fragment. Sequencing of this fragment revealed three putative open reading frames (ORFs) of 213 (far1), 152 (orf152) and 170 amino acids (orf170), which are flanked by the right-hand end of insertion sequence IS431/257 (IS431/257RH) and a partial ORF. Far1 and Orf152 demonstrated homology with a chromosomally encoded fibronectin-binding protein of Listeria monocytogenes and the putative protein YosT, found on the SP beta c2 prophage of Bacillus subtilis, respectively. Transformation of S. aureus with a construct containing a 949 bp far1-specific amplicon led to the isolation of a fusidic acid-resistant transformant, thereby identifying the pUB101 fusidic acid resistance structural gene. Between orf152 and far1 we identified a unique 113 bp symmetrical element and other repeat elements that may be involved with the control of orf152 and/or far1 expression. Hybridization of Southern blots revealed that far1 was not located on the chromosome or plasmid content of a limited number of Australian, UK and Hong Kong fusidic acid-resistant isolates. The pUB101 cadmium resistance determinant was located on a 3.6 kb HindIII fragment that carried a cadDX operon, remnants of two putative plasmid replication protein genes and IS431/257RH. Sequence analysis also demonstrated the presence of a single-stranded origin of replication, normally found on rolling circle replicating plasmids, within the putative promoter region of the cadDX operon.

Anti-Bacterial Agents↗
PubMed1993

Messenger-dependent action of the pokeweed antiviral protein and fusidic acid on in vitro Vicia sativa L. translation.

Plant ribosome sensitivity to either pokeweed antiviral protein (PAP) or fusidic acid has been investigated using a highly coupled translation system obtained from Vicia sativa L., a plant that lacks ribosome-inactivating protein activity. Protein synthesis directed by endogenous messengers was more sensitive to PAP than synthesis of polyphenylalanine directed by polyuridylic acid. Conversely, the effects of fusidic acid were the highest in polyphenylalanine synthesis. Additionally, the concentration of magnesium ions during translation also played a determinant role in the extent of inhibition by both PAP and fusidic acid. The effects seem to be exerted on the interaction of the translational elongation factor 2 with the ribosome.

Cell-Free System↗