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PubMed1999

Fusidic acid in skin and soft tissue infections.

Skin and soft skin tissue infections are usually caused by Staphylococcus aureus and Streptococcus pyogenes. In vitro data show good activity of fusidic acid against staphylococci but the minimal inhibitory concentrations for streptococci are relatively high indicating marginal activity. A limited number of clinical trials have been performed using oral fusidic acid and although all have methodological problems the difference in susceptibility of these two organisms is apparent. The end of study cure rates for these studies were 91-99% for S. aureus and 75-85% for S. pyogenes. Topical therapy has been used in a number of forms and for different skin infections. Comparative studies have been conducted with mupirocin, trimethoprim/polymixin cream, hydrogen peroxide and combination steroid preparations. For most of these studies fusidic acid was equivalent to the comparator agent except where there was a proven S. pyogenes infection. Studies with topical fusidic acid have also been reported in specific disease states such as acne, erythrasma, and abscesses with good results.

Administration, Oral↗
PubMed1989

Lack of activity of fusidic acid against human immunodeficiency virus in monocytes.

The effect of fusidic acid on the multiplication of human immunodeficiency virus in monocyte-derived macrophages was examined in in vitro cultures. Virus titers, measured by reverse transcriptase and by p24 antigen in the supernatants and in lysed cells, were reduced in some experiments by 50 micrograms/ml or more; in other experiments, 10 micrograms of fusidic acid per ml added to the cells simultaneously with the virus inoculation reduced virus titers. The effect was comparable in peripheral blood lymphocytes. The drug was generally toxic to the cells, both macrophages and peripheral blood lymphocytes, in concentrations of 50 micrograms/ml or more.

Fusidic Acid↗
PubMed1992

Levels of fusidic acid in skin blister fluid and serum after repeated administration of two dosages (250 and 500 mg).

The fusidic acid steady-state concentrations in serum (S) and skin suction blister fluid (SBF) after oral doses of 250 and 500 mg administered twice daily for 6 days, as film-coated tablets of sodium fusidate, were studied in eight healthy subjects. The mean peak serum concentrations after the 250- and 500- mg regimens were 39 +/- 5 and 102 +/- 11 mg/l, respectively, obtained between 2 and 3 h after drug intake. The corresponding values for SBF, obtained later, between 2 and 12 h after drug intake, were 21 +/- 5 and 79 +/- 11 mg/l. As measured by the ratio of area under the concentration vs. time curve (SBF/S), fusidic acid penetration is 69-75%, whatever the dose. With either regime, the fusidic acid SBF and serum levels exceed the minimal inhibitory concentration of bacteria usually found in skin infections, especially Staphylococcus species. A dose of 250 mg twice a day appears sufficient to treat these infections and could be tested in clinical studies.

Adult↗
PubMed2006

The influence of local instillation of fusidic acid on the development of microbial complications after lung resection.

The efficacy of local instillation of fusidic acid in the prevention of post-surgical microbial complications during various types of lung resection was studied. Four hundred ninety two consecutive patients who underwent 504 thoracotomies for non-small cell lung carcinoma during April 1998-May 2004 were reviewed. The 290 patients of the first period who underwent 298 thoracotomies received a chemoprophylactic regimen of intravenous cefuroxime while the 202 patients of the second period who underwent 206 thoracotomies were additionally treated with fusidic acid, irrigated with local instillation into the pleural space, for the prevention of postoperative septic complications. Patients were followed postoperatively for development of septic complications (empyema and bronchopleural fistula) as well as of pneumonia and wound infection. Seventeen patients (5.7%) of the first period developed empyema and 13 fistula (4.4%), whereas only 2 patients (1.0%) of the second period developed empyema and fistula (OR = 5.876; 95% CI, 1.343- 25.716; P = 0.008 and OR = 4.193; 95% CI, 1.003-20.130; P = 0.034, respectively). Cases of pneumonia decreased, but not significantly, from 21 (7.0%) during the first period to 9 (4.4%) during the second period (OR = 1.613; 95% CI, 0.724-3.593; P = 0.257) while cases of wound infection decreased significantly from 19 (6.4%) to 2 (1.0%) (OR = 6.567; 95% CI, 1.513-28.510; P = 0.003). During the first period 23 pathogens were found from cases of empyema and 73 pathogens from cases of pneumonia and wound infection, whereas during the second period 3 and 18 pathogens were respectively found (OR = 5.3; 95% CI, 1.570-17.888; P = 0.003, and OR = 2.804; 95% CI, 1.628-4.838; P <0.001, respectively). These results indicate that local instillation of fusidic acid in the pleural space prior to lung resection seems effective in reducing the rate of septic complications as well as of wound infections.

Aged↗
PubMed1991

Pharmacokinetics of fusidic acid in laboratory animals.

The ability of evaluate the efficacy of fusidic acid in animal models of infectious disease is limited by the absence of pharmacokinetic data for the agent in laboratory animals. In our study, aspects of fusidic acid pharmacokinetics were compared in rats (Rattus norwegicus), mice (Mus musculus), rabbits (Oryctolagus cuniculus), and guinea pigs (Cavia porcellus). Sodium fusidate was poorly absorbed after oral administration to rats, although limited absorption occurred in guinea pigs, mice, and rabbits. Subcutaneous injections of diethanolamine fusidate to laboratory rats, however, achieved a serum profile similar to that observed in humans. There was no evidence of drug accumulation in rats given repeated subcutaneous doses of diethanolamine fusidate during a 4-day period, but rabbits showed clear evidence of a cumulative effect.

Animals↗
PubMed2001

Mutations in the G-domain of elongation factor G from Thermus thermophilus affect both its interaction with GTP and fusidic acid.

Two hypersensitive and two resistant variants of elongation factor-G (EF-G) toward fusidic acid are studied in comparison with the wild type factor. All mutated proteins are active in a cell-free translation system and ribosome-dependent GTP hydrolysis. The EF-G variants with the Thr-84-->Ala or Asp-109-->Lys mutations bring about a strong resistance of EF-G to the antibiotic, whereas the EF-Gs with substitutions Gly-16-->Val or Glu-119-->Lys are the first examples of fusidic acid-hypersensitive factors. A correlation between fusidic acid resistance of EF-G mutants and their affinity to GTP are revealed in this study, although their interactions with GDP are not changed. Thus, fusidic acid-hypersensitive mutants have the high affinity to an uncleavable GTP analog, but the association of resistant mutants with GTP is decreased. The effects of either fusidic acid-sensitive or resistant mutations can be explained by the conformational changes in the EF-G molecule, which influence its GTP-binding center. The results presented in this paper indicate that fusidic acid-sensitive mutant factors have a conformation favorable for GTP binding and subsequent interaction with the ribosomes.

Alanine↗
PubMed1996

Disk diffusion interpretive criteria for fusidic acid susceptibility testing of staphylococci by the National Committee for Clinical Laboratory Standards method.

Fusidic acid is used in many countries for the treatment of multiresistant staphylococcal infection, especially multiresistant Staphylococcus aureus infection (MRSA). We collected consecutive fusidic acid-resistant isolates of staphylococci from the routine laboratory over several years, and compared these strains with fusidic acid-susceptible staphylococci to establish interpretive criteria for disk diffusion testing by National Committee for Clinical Laboratory Standards (NCCLS) methods. The minimum inhibitory concentrations (MICs) and zone diameters for strains of S. aureus (n = 102), including MRSA, S. saprophyticus (n = 20) and other coagulase-negative staphylococci (n = 115) were determined by NCCLS agar dilution and disk diffusion tests using a 2.5-micrograms disk of fusidic acid. MICs were bimodally distributed. No isolates had MICs of 0.5 or 1 microgram/ml; thus, we chose these values to define strains of intermediate susceptibility. The error-rate-bounded method was used to determine interpretive zone diameters for disk testing. Interpretive zone diameter criteria were found to be: susceptible > or = 22 mm, intermediate 18-21 mm, and resistant < or = 17 mm. All S. saprophyticus were intrinsically resistant to fusidic acid (MIC > or = 2 micrograms/ml).

Anti-Bacterial Agents↗
PubMed2006

Fusidic acid resistance, mediated by fusB, in bovine coagulase-negative staphylococci.

OBJECTIVES: The aim of this study was to determine the occurrence of fusidic acid resistance, mediated by the fusB gene, among coagulase-negative staphylococci (CoNS) isolated from bovine mastitis. METHODS: A total of 113 CoNS isolates were screened for susceptibility to fusidic acid by using a disc diffusion method. The fusB gene was detected by using PCR and subsequent DNA sequencing. The localization of fusB was determined by hybridization. RESULTS: The fusB gene was detected in 3 of 11 fusidic acid-resistant bovine CoNS isolates. The organization of the fusB downstream region on a 40 kb plasmid in a Staphylococcus haemolyticus isolate (288/96) was highly similar to the previously reported organization of fusB on plasmid pUB101 from a Staphylococcus aureus isolate of human origin. The fusB gene was chromosomally located in the remaining two isolates. CONCLUSIONS: Fusidic acid resistance mediated by fusB is not the dominant resistance mechanism in fusidic acid-resistant CoNS studied in this work. The similarity between the organization of the fusB downstream region in S. haemolyticus (isolate 288/96) and on plasmid pUB101 from an S. aureus isolate of human origin indicates a common ancestral origin of these genes.

Animals↗
PubMed1988

Effect of preoperative fusidic acid on the normal eyelid and conjunctival bacterial flora.

A randomised trial comparing the topical application of 1% fusidic acid with 0.3% gentamicin solution in the reduction of the normal preoperative lid and conjunctival microbial flora was performed. Forty patients awaiting cataract surgery were randomly divided into two groups consisting of 20 patients each. The first group received a 1% microcrystalline suspension of fusidic acid, the second 0.3% gentamicin to the preoperative eye every two hours between 0600 and 2400 daily for 48 hours preoperatively. Cultures were obtained from both the lid margins and the conjunctival sac of both groups prior to antibiotic therapy and again in the operating theatre before surgery. Microbiological identification and colony counts were performed by standard laboratory methods. Staphylococcus epidermidis was the commonest micro-organism isolated. Statistical analysis revealed no significant differences in the ability of a 1% microcrystalline suspension of fusidic acid and 0.3% gentamicin in eliminating or reducing the normal preoperative conjunctival or lid flora.

Administration, Topical↗
PubMed1989

[A multicenter randomized study of fusidic acid ophthalmic gel and rifamycine eyedrops in acute conjunctivitis].

A total of 163 patients with acute, presumably bacterial, conjunctivitis were included in a randomized trial, comparing: 1% fusidic acid viscous eye drops, a new ophthalmic formulation of fusidic acid instilled twice daily with rifamycin eye drops, four times daily. Both drugs were given 7 days long. Bacterial origin of the conjunctivitis, mainly staphylococcal, was proved in 75% of the cases. Overall, at the end of the treatment, a satisfactory response, on bacteriological and clinical grounds, was recorded for 87.3 and 89.5% of the patients in the Fucidin gel and rifamycin groups respectively. 9 and 12% of the patients in each group respectively, had a clinical recurrence 15 days after the treatment. No significant difference between the groups clinically and bacteriologically was noted. Side effects, mainly burning and smarting were noted by the investigators in 8 and 11 patients treated by fusilic acid and rifamycin respectively. Two patients were taken out of the study in the rifamycin group because of allergy. The difference between the groups is not significant. The use of fusidic acid viscous eye drops as compared to rifamycin eye drops was judged significantly easier by the patients (P less than 0.02), especially because of the reduced number of applications, the lack of color, and the lase of application.

Acute Disease↗
PubMed1983

Staphylococcal septicaemia complicated by probable cloxacillin neurotoxicity and by jaundice induced by fusidic acid.

Two weeks following a renal arteriogram a 56-year-old man with severe hypertension developed a staphylococcal septicaemia. After six weeks treatment with intravenous fusidic acid and cloxacillin he became icteric, confused and disorientated. The fusidic acid was stopped and the serum bilirubin fell to normal. His confusion persisted and serum cloxacillin levels were found to be grossly elevated. The patient's mental state returned to normal following withdrawal of cloxacillin. We attribute his jaundice to treatment with fusidic acid and his acute confusional state to cloxacillin neurotoxicity.

Cloxacillin↗
PubMedDate not supplied

[Neutropenia during treatment with fusidic acid: analysis of 5 cases].

Two cases of moderate neutropenia and 3 cases of severe neutropenia in the course of fusidic acid treatment for sepsis related to a hip prothesis or septic osteitis are reported. Neutropenia was always observed following routine blood cell count, after a mean of 21 days' treatment (16 to 27 days). Moderate fever was observed only once, in a patient with profound neutropenia. A complete recovery of blood cell count was noted in all cases, 5 to 9 days upon discontinuation of fusidic acid. A sternal bone-marrow aspiration was performed in 4 cases, showing normocellularity or hypercellularity in two cases, and moderate hypoplasia of granulocytic cells. The respective roles of other treatments are discussed. Overall, these five cases suggest that reversible granulocytopenia can be caused by protracted treatment with fusidic acid. Although nine different associated drugs could also have been involved in four patients, the causal relationship was less suggestive for three of them due to chronological events. In other cases, the drugs never or very rarely caused neutropenia. Finally, the possibility of vancomycin-induced neutropenia cannot be excluded in one case.

Aged↗
PubMed1999

Fusidic acid in the treatment of methicillin-resistant Staphylococcus aureus.

The emergence of MRSA in the 1960s coincided with the introduction of fusidic acid. Since that time, the antibiotic has been widely used against this organism, both in the 1960s and 1970s and against the more modern multi-resistant version of the 1980s and 1990s. Although showing potent in vitro activity, experimental in vivo and in vitro investigations have demonstrated disappointing results. Clinical efficacy has been demonstrated in a series of small studies and case reports, particularly when fusidic acid is used in combination for the treatment of MRSA carriage. Given the widespread use of fusidic acid against MRSA, published evidence supporting its efficacy is limited and does not support the use of the agent as monotherapy.

Anti-Bacterial Agents↗
PubMed1997

Effect of vancomycin and teicoplanin alone or in combination with fusidic acid or amikacin against methicillin-resistant staphylococci.

The action of two glycopeptides (vancomycin and teicoplanin) alone or in combination with amikacin or fusidic acid has been studied against 10 non-repetitive strains of methicillin-resistant Staphylococcus. The plotted killing curves show that the combination of vancomycin or teicoplanin plus fusidic acid always exhibited an antagonist effect at 24 h for the 10 strains. The combination vancomycin or teicoplanin plus amikacin shows the same effect at 24 h as vancomycin or teicoplanin alone. Thus, the combination glycopeptide plus amikacin does not alter the activity of the glycopeptide but does increase the spectrum of activity of the combination versus Gram-negative nosocomial bacteria (Pseudomonas aeruginosa, Acinetobacter sp). The vancomycin or teicoplanin plus fusidic acid combination may be responsible for bacteriological failure against methicillin-resistant Staphylococcus.

Amikacin↗
PubMed1985

Concentrations of fusidic acid, cloxacillin, and cefamandole in sera and atrial appendages of patients undergoing cardiac surgery.

The concentrations of cefamandole, cloxacillin and fusicid acid were measured in the serum and heart tissue of 100 recipients of these drugs before cardiac surgery. During cardiopulmonary bypass, mean (+/- standard deviation) peak concentrations in serum of all patients were 63.0 +/- 34.0 micrograms of cefamandole per ml, 30.8 +/- 17.7 micrograms of cloxacillin per ml, and 32.4 +/- 10.8 micrograms of fusidic acid per ml. Mean (+/- standard deviation) concentrations in atrial appendages taken 1 h (+/- 15 min) after infusion were 21.3 +/- 11.0 micrograms of cefamandole per g, 23.8 +/- 17.3 micrograms of cloxacillin per g, and 10.7 +/- 4.2 micrograms of fusidic acid per g. No cloxacillin could be detected in 5 of 39 heart specimens. Mean tissue-to-serum ratios at 1 h for cefamandole, cloxacillin, and fusidic acid were respectively 0.35, 0.73, and 0.33. Fusidic acid, a drug which is highly effective in vitro against both methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, was detectable in heart tissue in concentrations which were 12 times higher than the MICs of this agent against these resistant microorganisms.

Adult↗
PubMedDate not supplied

A comparative study between teicoplanin alone and flucloxacillin, plus or minus fusidic acid, in the treatment of serious infections caused by methicillin-susceptible gram-positive bacteria.

A randomized trial compared teicoplanin alone against flucloxacillin, with or without fusidic acid, in the treatment of serious gram-positive infections. The majority of infections involved Staphylococcus aureus or Staphylococcus epidermidis, methicillin-resistant organisms were excluded. A total of 56 patients were evaluable for efficacy, with no significant differences between treatment groups. Clinical success (cure + improvement) was achieved in 24/27 patients on teicoplanin (89%), 16 on flucloxacillin (100%) and 8/9 receiving flucloxacillin/fusidic acid (89%). Adverse events occurred in 21% of patients (7 on teicoplanin and 6 receiving flucloxacillin +/- fusidic acid). All such events resolved spontaneously or following appropriate management. It is concluded that teicoplanin monotherapy, 400 mg once daily, shows similar efficacy and tolerability to multiple daily doses of flucloxacillin, with or without fusidic acid, in the treatment of methicillin-susceptible serious gram-positive infection.

Adolescent↗
PubMed2004

Addition of fusidic acid impregnated bone cement to systemic teicoplanin therapy in the treatment of rat osteomyelitis.

We compared the efficacy of the combination of fusidic acid impregnated bone cement and systemic teicoplanin to systemic teicoplanin alone in implant-related osteomyelitis model in the rats. Foreign bodies were implanted into the medullary channels of 30 rat tibias after intramedullary inoculation of methicillin-resistant Staphylococcus aureus. Following proof of induction of osteomyelitis in the rats on the 21st day, a bone cement rod including 1/40 ratio of fusidic acid was inserted into the medullary channel of the tibias in the study group. Teicoplanin was administered i.m. at 20 mg/kg/day for 14 days to both the study and control groups. At the end of the treatment, the tibias were examined macroscopically, microbiologically and histopathologically. The elimination rate with the teicoplanin+fusidic acid combination was 81.8%, while with teicoplanin alone was 55.6% (p=0.33). Although the difference between the two groups was not statistically significant, the combination treatment had a positive effect in eliminating the microorganism.

Animals↗
PubMed1992

[In vitro kinetics of the activity of fusidic acid and fluoroquinolones combinations against staphylococci according to methicillin-resistance phenotype. Implications for the treatment of osteoarticular infections].

The kinetics of the effect of fusidic acid and of two fluoropiperazinyl quinolones (ofloxacin and pefloxacin), used alone or in combination, on ten methicillin-susceptible or methicillin-resistant strains of staphylococci were studied. Little or no bactericidal effects were seen with fusidic acid. With ofloxacin and pefloxacin, the bactericidal effect was delayed and occurred only with high concentrations. Used in combination, fusidic acid and the fluoroquinolones exhibited no synergistic effects and occasionally antagonized each other in vitro. The methicillin-resistance phenotype of organisms had no influence on results.

Bone Diseases↗