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PubMed2000

Structure of a mutant EF-G reveals domain III and possibly the fusidic acid binding site.

The crystal structure of Thermus thermophilus elongation factor G (EF-G) carrying the point mutation His573Ala was determined at a resolution of 2.8 A. The mutant has a more closed structure than that previously reported for wild-type EF-G. This is obtained by a 10 degrees rigid rotation of domains III, IV and V with regard to domains I and II. This rotation results in a displacement of the tip of domain IV by approximately 9 A. The structure of domain III is now fully visible and reveals the double split beta-alpha-beta motif also observed for EF-G domain V and for several ribosomal proteins. A large number of fusidic acid resistant mutations found in domain III have now been possible to locate. Possible locations for the effector loop and a possible binding site for fusidic acid are discussed in relation to some of the fusidic acid resistant mutations.

Amino Acid Motifs↗
PubMed1990

Clinical experiences with fusidic acid in cystic fibrosis patients.

A survey of Staphylococcus aureus lung infection in 243 patients with cystic fibrosis (CF) was conducted between 1986 and 1988. A total of 217 patients (89%) received 1605 courses of anti-staphylococcal therapy given during this period. The majority of courses comprised combined therapy with two anti-staphylococcal drugs. The combination of dicloxacillin and fusidic acid was employed most frequently. Some patients were given other anti-staphylococcal regimens, because of penicillin allergy (14 cases) or dyspeptic side effects with fusidic acid (21 patients). A small but significant increase in precipitins against S. aureus was observed during the study period. Bacterial resistance to the anti-staphylococcal drugs used remained at a low level (strains resistant to methicillin less than 0.1%, strains resistant to fusidic acid 1.2%). When the isolates were compared with 56,140 strains of S. aureus isolated from non-CF patients hospitalized in Denmark over the same period, no differences in phagetypes or in antibiotic resistance were seen, indicating that selection of strains and cross infection do not seem to be a major problem in CF patients.

Bacteriophage Typing↗
PubMed2002

[In vitro sensitivity of methicillin-resistant Staphylococcus aureus to fusidic acid and trimethoprim-sulfamethoxazole].

In this study, a total of 225 methicillin resistant Staphylococcus aureus strains isolated from various clinical specimens (114 wounds, 27 blood, 16 of each catheter and sputum, 14 throat swabs, 10 tracheal aspirates, 7 of each urine and drain materials, 6 pleural fluids, 5 graft materials, 2 cerebrospinal fluids, 1 ascitis fluid) of hospitalized patients, were tested in-vitro for their susceptibilities to fusidic acid and trimethoprim-sulfamethoxazole (TMP-SMX) by disk diffusion method. Two-hundred-eighteen (96.9%) of isolates were found susceptible to both fusidic acid and TMP-SMX, 4 (1.8%) were resistant to both of the agents (3 isolates from wound, 1 from sputum), 2 (0.9%) (both of them were wound isolates) were resistant only to fusidic acid, and 1 (0.4%) (throat isolate) was resistant only to TMP-SMX.

Anti-Bacterial Agents↗
PubMed1986

Interaction between rifampin and fusidic acid against methicillin-resistant coagulase-positive and -negative staphylococci.

We studied the interaction between rifampin and fusidic acid against a group of staphylococci. Of the 20 coagulase-positive strains studied, checkerboard studies revealed synergy in 3 and indifference in 17; time-kill studies revealed synergy in 18 of 19 coagulase-positive strains at both 24 and 48 h. Of the 19 coagulase-negative strains, checkerboard studies revealed synergy in 6 and indifference in 13; time-kill studies revealed synergy in 6 of 18 coagulase-negative strains at 24 h and in 17 of 18 coagulase-negative strains at 48 h. The combination of rifampin and fusidic acid warrants further evaluation in the therapy of staphylococcal disease.

Coagulase↗
PubMed2002

Calibration of fusidic acid disk diffusion susceptibility testing of Staphylococcus areus.

Single strain regression analysis, SRA, was used to calibrate disk diffusion fusidic acid susceptibility testing of Staphylococcus aureus in two laboratories using different standard methods but the same interpretative MIC limits. SRA equation constants were calculated using five different fusidic acid disk contents (1.5, 5, 15, 50, 150 microg). These disks were tested on five separate occasions against quality control strain S. aureus ATCC 29213. The National Committee for Clinical Laboratory Standards (NCCLS) method was employed in Tartu, Estonia (TE) and the Swedish Reference Group for Antibiotics (SRGA) method in Sweden at the Karolinska Hospital (KS). SRA constants obtained were used for calculating zone breakpoints corresponding to MIC breakpoints recommended by the SRGA (S < or = 0.5 mg/L, R > or = 1 mg/L). Zone diameter histograms from KS, performed with a 50 microg disk, and from TE, using a 10 microg disk, showed a clustering of wild type strains around 41 mm and 30 mm, respectively, reflecting differences in methodology. Zone breakpoints calculated from the equations were validated by comparison with the histograms. Breakpoints were also calculated for a suggested lower disk content in Sweden, 10 microg, and validated in tests of clinical isolates and by histogram analysis.

Anti-Bacterial Agents↗
PubMed1979

Effects of cloxacillin, doxycycline, fusidic acid and lincomycin on the mechanical properties of bone and skin in young rats.

The influence of cloxacillin, doxycycline, fuside acid and lincomycin on the mechanical properties of bone and skin in young rats was examined. The concentrations of the antibiotics in plasma corresponded to therapeutic levels in man. After 14 days of medication the weights of the rats receiving cloxacillin or doxycycline were significantly less when compared with the controls. The doxycycline, the fusidic acid and the lincomycin treated rats had reduced longitudinal growth of femur and reduced tensile strength of intact skin. No differences between any of the antibiotic groups and the control group were found in the tensile strength of incisional skin wounds or in the mechanical properties of the femur and tibia.

Animals↗
PubMedDate not supplied

Trimethoprim-polymyxin B sulphate cream compared with fusidic acid cream in the treatment of superficial bacterial infection of the skin.

Trimethoprim-polymyxin B sulphate cream or fusidic acid cream was used to treat 64 patients with primary or secondary superficial bacterial infections of the skin in a randomized, double-blind controlled trial. Both treatments were effective in alleviating the clinical signs and symptoms associated with bacterial infection. A cream containing a combination of 0.17 mg/g trimethoprim and 10,000 IU/g polymyxin B sulphate was, however, significantly more effective than a 20 mg/g fusidic acid cream in reducing the signs of crust and tenderness.

Adolescent↗
PubMed1995

Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus.

Mupirocin is a topically applied drug that is very active in the eradication of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, studies designed to compare mupirocin treatment with other antimicrobial regimens are lacking. We therefore conducted an open, prospective, randomized, controlled trial to compare the efficacy and safety of mupirocin versus those of oral co-trimoxazole plus topical fusidic acid (both regimens with a clorhexidine scrub bath) for the eradication of MRSA from nasal and extranasal carriers of MRSA. The eradication rates with mupirocin and co-trimoxazole plus fusidic acid at 2, 7, 14, 21, 28, and 90 days were 93 and of 93, 100 and 100, 97 and 94, 100 and 92, 96 and 95, and 78 and 71%, respectively, for nasal carriage. At 7, 14, and 28 days the eradication rates for extranasal carriage by the two regimens were 23 and 74, 83 and 76, and 45 and 69%, respectively. The efficacies and safety of both regimens were similar. The MRSA isolates were not resistant to the study drugs either at the baseline or at follow-up. These results suggest that mupirocin and co-trimoxazole plus fusidic acid, both used in conjunction with a chlorhexidine soap bath, are equally effective and safe for the eradication of MRSA from nasal and extranasal MRSA carriers. Mupirocin was easier to use but was more expensive.

Administration, Oral↗
PubMed1993

Susceptibility of Mycobacterium kansasii to ofloxacin, sparfloxacin, clarithromycin, azithromycin, and fusidic acid.

The MICs of ofloxacin, sparfloxacin, clarithromycin, azithromycin, and fusidic acid for clinical isolates of Mycobacterium kansasii were determined by the radiometric (BACTEC) method. All drugs except azithromycin elicited MICs for 90% of the strains tested that were lower than previously reported achievable maximum concentrations in serum. Ofloxacin, sparfloxacin, and clarithromycin had the largest maximum concentration in serum/MIC for 90% of strains ratio of the drugs tested.

4-Quinolones↗
PubMed1990

Fusidic acid treatment of HIV infection: no significant effect in a pilot trial.

22 HIV-positive homosexual men were treated with fusidic acid tablets (500 mg t.i.d.) for a period of 2-12 months (mean 71/2). At entry, all had a CD4-count less than 500 X 10(6)/l, and/or a pokeweed mitogen lymphocyte proliferation response of less than 50% of 2 normal controls, and no overt opportunistic infections. No significant immunological changes were observed and no definite beneficial clinical effect. On the 10th-13th day of treatment, 12 of the patients developed fever and an itchy exanthema. The symptoms disappeared spontaneously in 9 patients. No hematological or biochemical side effects were seen. Thus, in this pilot study of fusidic acid therapy of HIV-infected men, no significant effect could be detected.

Fusidic Acid↗
PubMed2003

In vitro bactericidal activities of linezolid in combination with vancomycin, gentamicin, ciprofloxacin, fusidic acid, and rifampin against Staphylococcus aureus.

The in vitro activities of linezolid were determined alone and in combination with vancomycin, ciprofloxacin, gentamicin, fusidic acid, or rifampin against five methicillin-susceptible Staphylococcus aureus (MSSA) and five methicillin-resistant S. aureus (MRSA) strains. Similar responses were obtained against MSSA and MRSA. When combined with fusidic acid, gentamicin, or rifampin, linezolid prevented selection of resistant mutants but showed no synergy. When linezolid was combined with vancomycin and ciprofloxacin, a slight antagonism was observed. While the combination with linezolid may reduce the emergence of mutants resistant to the associated drugs, the absence of synergy, especially in the case of vancomycin and ciprofloxacin, does not argue in favor of such combinations.

Acetamides↗
PubMed2000

[Predominance of multidrug resistant strains with reduced susceptibility to fusidic acid among methicillin-resistant Staphylococcus aureus strains (MRSA) isolated in the Gdánsk region].

The aim of the present study was to follow the changes in the drug resistance among the methicillin-resistant Staphylococcus aureus strains (MRSA) isolated from clinical samples in various hospitals during 8 years, with particular consideration of Gdansk area. The study was carried out on 225 strains of MRSA from which 95 were isolated in the years 1990-1995 and 130 in the years 1997-1998. The drug susceptibility was determined by the disc-diffusion method. The sensitivity to fusidic acid was determined by both disc-diffusion method and minimal inhibitory concentration (MIC) using agar dilutions. The results obtained show that in 1997-1998 in the hospitals of Gdansk area have been appeared MRSA strains which have not occurred before. These strains were intermediately sensitive or resistant to fusidic acid and simultaneously resistant to doxycycline, gentamicin, erythromycin, clindamycin, ciprofloxacin and rifampin. They represented 66.2% of all MRSA strains isolated in 1997-1998 and were present in majority of the hospitals monitored. Only in this group of staphylococci the strains additionally resistant to mupirocin (6.2%) occurred. Among the MRSA strains with reduced susceptibility to fusidic acid 64.4% were intermediately sensitive (MIC 8-16 mg/L) and 15.4% were resistant to this drug (MIC > 16). In 1997-1998 the percentages of MRSA strains resistant to rifampin, clindamycin and ciprofloxacin increased significantly from 12.6% to 90.8%, from 42.1% to 92.3% and from 18.9% to 92.3% respectively. The percentage of the chloramphenicol resistant strains decreased from 14.7% to 0.8%. Like in 1990-1995, the MRSA strains resistant to vancomycin and teicoplanin were not found out in the same period of time.

Drug Resistance, Multiple↗
PubMed1987

Polyvalent inhibitory action of fusidic acid in isolated rat liver cells.

The steroidic antibiotic fusidic acid showed a polyvalent action on isolated rat liver cells. It displayed a strong inhibitory capability on protein synthesis in intact cells even stronger than that previously reported in cell-free extracts. Also, it inhibited basal gluconeogenesis and promoted an increase of the membrane permeability to trypan blue. However, the effects on both protein synthesis and basal gluconeogenesis were observed at doses smaller than those required to reduce the cell viability.

Animals↗
PubMed1981

Treatment of neonatal osteomyelitis with cloxacillin in combination with fusidic acid.

Four immature infants developed staphylococcal neonatal osteomyelitis. In spite of standard treatment with cloxacillin, gentamicin and surgical drainage new lesions developed in all 4 patients. Following the addition of fusidic acid no further progress was seen in any of the infants. Fusidic acid was administered intravenously for 10-14 days in a dose of 40 mg/kg/day in 2 divided doses. The therapy was well tolerated. Thoracic kyphosis in one patient was the only sequelae seen.

Cloxacillin↗
PubMed1993

In vitro activities of ceftriaxone and fusidic acid against 13 isolates of Coxiella burnetii, determined using the shell vial assay.

The susceptibilities of 13 isolates of Coxiella burnetii to fusidic acid and ceftriaxone were determined by use of the recently described shell vial assay (D. Raoult, H. Torres, and M. Drancourt, Antimicrob. Agents Chemother, 35:2070-2077, 1991). At a concentration of 4 micrograms/ml, ceftriaxone was bacteriostatic for four isolates and slowed the multiplication of the other nine. Fusidic acid at a concentration of 2 micrograms/ml was bacteriostatic for six isolates and slowed the multiplication of three others. These results show that these compounds could be effective in the phagolysosome of C. burnetii-infected cells.

Ceftriaxone↗
PubMed1990

Antibacterial activity of teicoplanin and vancomycin in combination with rifampicin, fusidic acid or fosfomycin against staphylococci on vein catheters.

The bactericidal activities of teicoplanin and vancomycin, as single agents or combined with fosfomycin, fusidic acid or rifampicin, were investigated in an in vitro study involving 20 strains of Staphylococcus epidermidis isolated from infected vein catheters. Greater antibacterial effects were exhibited against certain bacterial strains by the combined antibiotics, rather than by teicoplanin or vancomycin alone. The vancomycin-fusidic acid combination showed less of a bactericidal effect than all other combinations. The strongest bactericidal effects on all strains were exhibited by the combinations of teicoplanin and vancomycin with rifampicin. These results may be important for the antibiotic treatment of staphylococcal infections of vein catheters, if immediate removal of an infected catheter is not possible.

Catheters, Indwelling↗
PubMed2000

Observations on high levels of fusidic acid resistant Staphylococcus aureus in Harrogate, North Yorkshire, UK.

A retrospective study was carried out to investigate possible reasons for a marked increase in fusidic acid-resistant Staphylococcus aureus (FusR S. aureus) identified by our routine hospital microbiology service. Information was obtained on a sample of 64 consecutive patients from whom resistant S. aureus had been cultured. The source of isolates was found to be diffuse within the hospital and community. The site of sample was most frequently chronic cutaneous infections (68%). All the S. aureus isolates were resistant to both fusidic acid and penicillin and many were resistant to multiple antibiotics. Topical fusidic acid had been used by 40% of patients in the preceding 6 months and none had received oral fusidic acid (sodium fusidate). Most (80%) had received an oral antibiotic in the preceding 2 years. Information from the Prescriptions Pricing Authority revealed that the total number of prescriptions for fusidic acid-containing preparations for the period September 1997 to August 1998 was markedly higher in Harrogate than in five other local areas where increases in (FusR) S. aureus have not been observed.

Administration, Oral↗