Formation of fusidic acid-G factor-GDP-ribosome complex and the relationship to the inhibition of GTP hydrolysis.
Explore the source record for details and available documents.
Carbon Isotopes↗
SEARCH · Search PubMed
Results for “FUSIDIC ACID”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Structure-activity relationships in fusidic acid-type antibiotics.
Explore the source record for details and available documents.
Acremonium↗
Antimicrobial agents and host defence.
Reports from different laboratories on effects of different antibiotics on host defence are often hard to compare because of differences in experimental design. The purpose of this presentation was to describe the effect of many different antibiotics with the same standardized techniques. E. coli and S. aureus pre-exposed to different beta-lactam antibiotics or gentamicin in subinhibitory concentrations were more susceptible to phagocytosis and killing by granulocytes than non-treated bacteria. A markedly depressed chemotaxis was detected when human leucocytes were incubated with fusidic acid and rifampicin in clinically obtainable concentration and well absorbed tetracyclines at high concentrations. The incorporation of 14C-leucine into a trichloracetic-acid insoluble form by human neutrophils was markedly depressed by the same antibiotics. Many other antibiotics did not inhibit granulocyte or lymphocyte functions. At therapeutic concentrations fusidic acid and rifampicin had a pronounced inhibition effect on the incorporation of 3H-thymidine by human T-lymphocytes stimulated by PHA and B-lymphocytes by S. aureus, Cowan I. At concentrations above the therapeutic level, inhibition was detected for doxycycline, erythromycin, clindamycin and nitrofurantoin. Due to high albumin binding for some of the tested antibiotics and other factors involved, experiments were performed to test whether depression also takes place in vivo. The cellular immunity in mice was registered by monitoring the survival of transplanted heart grafts. Rifampicin at human therapeutic dose had a strong inhibiting effect (p less than 0.001) on the rejection of heart grafts. The effect of doxycycline (2.5 mg/kg/day) and fusidic acid (25 mg/kg/day) was slight but significant (p less than 0.02).
Animals↗
[Changes of methicillin-resistant Staphylococcus aureus (MRSA) phagotypes in Gdansk in 1990-1998].
The aim of the study was the assessment of changes in the occurrence of various MRSA phagotypes in hospitals in the Gdańsk area in 1990-1998. The study was carried out on 175 MRSA strains: 45 strains isolated in 1990-1995 and 130 in 1997-1998. The studied staphylococci were obtained from various clinical materials from patients in 18 hospitals. Phagotyping was done with a set of 10 experimental phages from MRSA strains obtained from the Central Public Health Laboratory in London. Drug-resistance was determined by the disc-diffusion method and in case of strains with medium susceptibility to fusidic acid the minimal inhibitory concentration (MIC) was determined by serial dilutions on solid medium. The study showed among MRSA strains isolated in 1997-1998 a new, previously not known strains with phage pattern MR25/M5 predominated (57.7%). Its presence was found in various hospitals in that area. MRSA belonging to MR25/M5 phagotype were mostly resistant to doxycycline, gentamycin, erythromycin, clindamycin, ciprofloxacin, rifampicin and were resistant or only had medium susceptibility to fusidic acid. The MIC values for strains with medium susceptibility to fusidic acid (4-8 micrograms/ml) showed an evident decrease of the susceptibility to this antibiotic, formerly common in MRSA. At the same time, in 1997-1998 a considerable decrease was observed of the number of MRSA strains belonging to MR8/MR12/MR25/30/33/38/M5/622 phagotype (from 31.1% to 0.8%), and disappearance of strains with phagotypes MR25/56B/M3 and MR8/MR25/622, which in 1990-1995 accounted for 15.6% of the studied staphylococci.
Bacteriophage Typing↗
Dissociation of intact Escherichia coli ribosomes in a mass spectrometer. Evidence for conformational change in a ribosome elongation factor G complex.
We used mass spectrometry to identify proteins that are released in the gas phase from Escherichia coli ribosomes in response to a range of different solution conditions and cofactor binding. From solution at neutral pH the spectra are dominated by just 4 of the 54 ribosomal proteins (L7/L12, L11, and L10). Lowering the pH of the solution leads to the gas phase dissociation of four additional proteins as well as the 5 S RNA. Replacement of Mg(2+) by Li(+) ions in solutions of ribosomes induced the dissociation of 17 ribosomal proteins. Correlation of these results with available structural information for ribosomes revealed that a relatively high interaction surface area of the protein with RNA was the major force in preventing dissociation. By using the proteins that dissociate to probe their interactions with RNA, we examined different complexes of the ribosome formed with the elongation factor G and inhibited by fusidic acid or thiostrepton. Mass spectra recorded for the fusidic acid-inhibited complex reveal subtle changes in peak intensity of the proteins that dissociate. By contrast gas phase dissociation from the thiostrepton-inhibited complex is markedly different and demonstrates the presence of L5 and L18, two proteins that interact exclusively with the 5 S RNA. These results allow us to propose that the ribosome elongation factor-G complex inhibited by thiostrepton, but not fusidic acid, involves destabilization of 5 S RNA-protein interactions.
Escherichia coli Proteins↗
Antibiotic treatment of abscesses of the central nervous system.
Samples of intracranial pus and serum from 32 patients were assayed to determine the concentrations reached in them of penicillin, ampicillin, cloxacillin, cephaloridine, gentamicin, chloramphenicol, fusidic acid, and lincomycin. Metronidazole had not been given. Penicillin penetrated abscesses reasonably well, but other beta-lactam antibiotics did not. The penetration of chloramphenicol was erratic. Aminoglycosides penetrated poorly, but lincomycin and fusidic acid penetrated well. Assay of sulphonamides and co-trimoxazole in pus was unreliable. These studies indicate that treatment of abscesses of the central nervous system should be considered according to the site and the likely antecedent cause. Abscesses of sinusitic origin, usually in the frontal lobe, yield penicillin-sensitive streptococci. Penicillin is the drug of choice. Abscesses of otitic origin, usually in the temporal lobe, yield a mixed flora, often including anaerobic bacteria. Multiple antibiotic therapy is indicated. Abscesses of metastatic or cryptogenic origin yield streptococci or mixed cultures, and multiple therapy is appropriate while awaiting the bacteriological results. Spinal and post-traumatic abscesses yield Staphylococcus aureus, and fusidic acid is the drug of choice.
Abscess↗
Fusidane antibiotics produced by dermatophytes.
Isolates of Microsporum canis, Microsporum gypseum and Epidermophyton floccosum were observed to produce antibacterial activities under cross-resistance to fusidic acid. The activity from E. floccosum was shown to be due to fusidic acid, diketofusidic acid and 3-ketofusidic acid. Possible contributions of these antibiotics to microbial interaction during dermatophytosis is discussed.
Anti-Bacterial Agents↗
Gentamicin- and methicillin-resistant Staphylococcus aureus: in vitro susceptibility to antimicrobial drugs.
Thirteen nosocomially significant, gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus isolates, all of phage group III/M (lysotype 42E/47/53/54/75/77/83A/84/85/94/96), were uniformly resistant against augmentin, erythromycin, fosfomycin, gentamicin, methicillin, oxacillin, penicillin G, tetracycline, and tobramycin, but differed in susceptibility to cefamandole, ciprofloxacin, clindamycin, imipenem, josamycin, the synthetic chinolone Ro 23-6240, and ofloxacin. All isolates were susceptible to chloramphenicol, coumermycin, fusidic acid, novobiocin, rifampin, teicoplanin, trimethoprim-sulfamethoxazole (cotrimoxazole), and vancomycin. One isolate was of intermediate susceptibility to netilmicin. On a weight-for-weight basis, the 7 most active drugs were rifampin, coumermycin, cotrimoxazole, novobiocin, teicoplanin, fusidic acid, and vancomycin (in decreasing order) in terms of minimal inhibitory concentrations. With regard to minimal bactericidal concentrations, coumermycin, rifampin, vancomycin, teicoplanin, cotrimoxazole, ofloxacin, and ciprofloxacin (in decreasing order) were the 7 most potent antimicrobial drugs. Freshly defibrinated human blood [65% (v/v)] combined with chloramphenicol and rifampin, respectively, resulted in a weak additive effect (time kill curves). Indifferent effects were observed following combination of blood with ciprofloxacin, cotrimoxazole, coumermycin, fusidic acid, imipenem, netilmicin, novobiocin, ofloxacin, compound Ro 23-6240, teicoplanin, and vancomycin. Rifampin combined with novobiocin, teicoplanin, and vancomycin, respectively, in the presence of 65% (v/v) human blood, resulted in an additive effect. Combinations of rifampin with 9 other antimicrobial drugs in blood yielded essentially indifferent effects.
Anti-Bacterial Agents↗
In vitro activity of combinations of antibiotics against Staphylococcus aureus resistant to gentamicin and methicillin.
Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.
Aminoglycosides↗
Purification and N-terminal sequence analysis of pea chloroplast protein synthesis factor EF-G.
Chloroplast protein synthesis elongation factor G (chlEF-G) has been purified from whole-cell extracts of light-induced pea (Pisum sativum) seedlings. The first step in the purification scheme relies on the affinity of organellar EF-G for Escherichia coli ribosomes in the presence of the antibiotic, fusidic acid. A complex between organellar EF-G, E. coli ribosomes, GDP, and fusidic acid was isolated by high-speed centrifugation. The largest major protein eluted from this complex by high salt has an apparent molecular weight of 86,000 and is only a minor component of similar preparations from dark-grown seedlings. The same polypeptide copurifies with EF-G activity upon size exclusion HPLC on a Waters Protein-Pak 200SW column. The N-terminal amino acid sequence of chlEF-G has been determined by direct sequencing of gel-purified protein. Like many proteins that are processed upon import into chloroplasts, it has an N-terminal alanine residue. Part of the putative chlEF-G gene has been amplified using oligonucleotides corresponding to the N-terminal amino acid sequence of the purified protein and to highly conserved sequences within the GTP-binding domains of other elongation factors. The deduced amino acid sequence displays high sequence identity to the corresponding region of the chloroplast EF-G gene product from soybean, somewhat less similarity to bacterial EF-Gs, and only low homology to mitochondrial EF-G and to eukaryotic cytoplasmic EF-2 genes. The chlEF-G gene appears to be encoded by a two-copy gene family in pea and a single-copy gene in Arabidopsis thaliana.
Amino Acid Sequence↗
Staphylococcus aureus sensitivity to various antibiotics--a national survey in Ireland 1993.
The sensitivity of Staphylococcus aureus (S. aureus) to methicillin, penicillin, gentamicin, erythromycin, ciprofloxacin, fusidic acid and mupirocin was tested in 1152 clinical isolates from nine hospital microbiology departments. In all cases standard methods for culture and sensitivity were employed using either the Stokes' or a modified Stokes' method for susceptibility testing. The isolates were recovered from 1150 patients (606 men, 544 women; mean age: 41 years) and only those deemed relevant to the patient's clinical condition were included. Of the total 1152 isolates, 454 were regarded as hospital acquired, 506 were community acquired and the source of the remaining 192 isolates was unknown. The overall percentages of S. aureus sensitive to the tested antibiotics were as follows: methicillin 85%, penicillin 8%, gentamicin 89%, ciprofloxacin 85%, erythromycin 80%, fusidic acid 96%, mupirocin 98%. The sensitivity of the methicillin resistant strains to the other antibiotics tested was generally low except for fusidic acid and mupirocin, both of which retain good activity against methicillin resistant S. aureus (MRSA).
Aged↗
Interventions for impetigo.
BACKGROUND: Impetigo is a common superficial bacterial skin infection, most frequently encountered in children. There is no standard therapy and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. OBJECTIVES: To assess the effects of treatments for impetigo, including waiting for natural resolution. SEARCH STRATEGY: We searched the Skin Group Specialised Trials Register (March 2002), Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2002), the National Research Register (2002), MEDLINE (from 1966 to January 2003), EMBASE (from 1980 to March 2000) and LILACS (November 2001). We handsearched the Yearbook of Dermatology (1938-1966), the Yearbook of Drug Therapy (1949-1966), used reference lists of articles and contacted pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials of treatments for non-bullous and bullous, primary and secondary impetigo. DATA COLLECTION AND ANALYSIS: All steps in data collection were done by two independent reviewers. We performed quality assessments and data collection in two separate stages. MAIN RESULTS: We included 57 trials including 3533 participants in total which studied 20 different oral and 18 different topical treatments. CURE OR IMPROVEMENT: Topical antibiotics showed better cure rates than placebo (pooled odds ratio (OR) 6.49, 95% confidence interval (CI) 3.93 to 10.73), and no topical antibiotic was superior (pooled OR of mupirocin versus fusidic acid 1.76, 95% CI 0.69 to 2.16). Topical mupirocin was superior to oral erythromycin (pooled OR 1.22, 95% CI 1.05 to 2.97). In most other comparisons, topical and oral antibiotics did not show significantly different cure rates, nor did most trials comparing oral antibiotics. Penicillin was inferior to erythromycin and cloxacillin and there is little evidence that using disinfectant solutions improves impetigo. SIDE EFFECTS: The reported number of side effects was low. Oral antibiotic treatment caused more side effects, especially gastrointestinal ones, than topical treatment. REVIEWERS' CONCLUSIONS: Data on the natural course of impetigo are lacking. Placebo controlled trials are scarce. There is little evidence about the value of disinfecting measures. There is good evidence that topical mupirocin and topical fusidic acid are equally, or more effective than oral treatment for people with limited disease. It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. Resistance patterns against antibiotics change and should be taken into account in the choice of therapy.
Administration, Oral↗
Purification and characterization of the mitochondrial translocase from Euglena gracilis.
The Euglena gracilis mitochondrial protein biosynthetic elongation factor G (EF-Gmt) has been purified in four steps to greater than 50% homogeneity by use of a fusidic acid affinity procedure and conventional chromatographic techniques. The purification scheme results in 1100-fold purification with about 3% recovery of the total EF-G activity present in the postribosomal supernatant prepared from whole cell extracts. E. gracilis EF-Gmt has an approximate molecular weight of 76,000, comparable to that observed for procaryotic translocases. As is the case for other translocases which have been examined, pretreatment of E. gracilis EF-Gmt with N-ethylmaleimide results in a loss of polymerization activity, indicating a role for an essential cysteine residue in catalytic activity. GDP partially protects EF-Gmt from N-ethylmaleimide inactivation. E. gracilis EF-Gmt functions well on both Escherichia coli and E. gracilis chloroplast ribosomes, but has negligible activity on wheat germ cytoplasmic ribosomes. In this respect, it differs significantly from the mitochondrial translocase of yeast which has very little activity on chloroplast ribosomes. When assayed on E. coli ribosomes, E. gracilis EF-Gmt is sensitive to the steroid antibiotic, fusidic acid, at levels similar to that required for inactivation of E. coli EF-G. It is less sensitive than E. gracilis chloroplast EF-G, and is more sensitive than Bacillus subtilis EF-G. When assayed on E. gracilis chloroplast ribosomes, the same trends in sensitivities are observed, although the exact level of fusidic acid required for inactivation is slightly altered.
Bacillus subtilis↗
Influence of guanine nucleotides and elongation factors on interaction of release factors with the ribosome.
Release of formylmethionine from the reticulocyte ribosomal substrate, f[(3)H]Met-tRNA.ribosome, is promoted by reticulocyte release factor (RF). The initial rate of this reaction is stimulated by GTP but inhibited by GDPCP. Formation of an RF.UA[(3)H]A(2).ribosome complex is a measure of the binding of reticulocyte RF to the ribosome, and the recovery of this complex is increased by GDPCP and, to a lesser extent, GTP. These studies suggest that GTP is involved in the initial association of RF with the ribosome and that hydrolysis of the gamma-phosphate of the guanine nucleotide is required at a subsequent rate-limiting step. The ribosomal-dependent fMet-tRNA hydrolysis and GTPase activities of reticulocyte RF are inhibited when elongation factor (EF)-2 is bound to the respective ribosomal substrate in the presence of fusidic acid and GDP. When EF-G is bound to the f[(3)H]Met-tRNA.AUG.ribosome substrate with fusidic acid and GDP, the fMet-tRNA hydrolysis activity of Escherichia coli RF-1 and RF-2 is also inhibited. The binding of reticulocyte RF and E. coli RF-1 or RF-2 to their respective ribosomes is prevented when fusidic acid.EF-2/EF-G.GDP.ribosome complexes are used.
Animals↗
Antibiotic treatment of Staphylococcus aureus infection in cystic fibrosis.
During the period 1965-79 191 cystic fibrosis patients have been treated with 2349 course of anti-staphylococcal chemotherapy in the Danish Cystic Fibrosis Centre. The standard treatment was orally administered Fusidic acid in combination with Oxacillin or Dicloxacillin given for 14 days. In cases of penicillin allergy Fusidic acid in combination with Rifampicin was given. The overall results showed that S. aureus was eradicated from sputum by a single course of chemotherapy in 74% of the cases, although in 8% the original strains (phage-type) was replaced by a new strain. Repeated or extended treatment was successful in most of the remaining cases and, as a result, only 9% of our patients harboured S. aureus continuously for 6 months or more. On the average each patient received 2 anti-staphylococcal treatment per year, but no decrease in efficacy of repeated treatment was seen. Likewise, no significant increase of S. aureus precipitins and no development of resistant strains was seen in our patients. Due to the efficacy of chemotherapy and the principles of early treatment whether there are clinical symptoms of infection or not, S. aureus infection is now considered a minor problem without relation to poor prognosis in our cystic fibrosis patients.
Adolescent↗
In vitro activity of ciprofloxacin against gram-positive cocci.
In vitro studies compared the activities of ciprofloxacin, vancomycin, and fusidic acid against staphylococci, streptococci, and enterococci. Against 111 methicillin-resistant and 162 methicillin-susceptible staphylococcal strains, fusidic acid was the most potent of the three drugs (minimal inhibitory concentration [MIC] for 90 percent of the strains was 0.06 microgram/ml). Ciprofloxacin and vancomycin were also effective anti-staphylococcal drugs (MIC of ciprofloxacin for 90 percent of the strains was 0.5 microgram/ml and of vancomycin was 1.0 microgram/ml). Ciprofloxacin had a more rapid bactericidal effect against staphylococci than did vancomycin. Neither vancomycin nor ciprofloxacin alone had useful bactericidal activity against enterococci. Streptococci were only marginally susceptible to ciprofloxacin (MIC for 90 percent of the strains was 1.0 to 4.0 micrograms/ml for different species). Vancomycin was superior to ciprofloxacin in its anti-streptococcal activity (MIC for 90 percent of the strains was 0.25 to 0.5 microgram/ml). The promising in vitro anti-staphylococcal activity of ciprofloxacin deserves further consideration in clinical trials.
Ciprofloxacin↗
MICROBIOLOGICAL ACTIVITIES OF LYSOSTAPHIN AND PENICILLINS AGAINST BACTERIOPHAGE 80/81 STRAINS OF STAPHYLOCOCCUS AUREUS.
Using 20 clinical isolates of S. aureus (all bacteriophage 80/81 type), we found that lysostaphin inhibits the growth of all cultures at concentrations significantly lower than those observed with any of eight penicillins, a penicillin-like compound (cephalothin), or fusidic acid (a steroid antibiotic). All test cultures were shown to be resistant to penicillin G, ampicillin, and propicillin. Of the remaining penicillins (all penicillinase-insensitive), oxacillin, nafcillin, cloxacillin, and cephalothin were approximately equal in antimicrobial activity. Ancillin was slightly less active, and methicillin was even lower in potency. Cultures varied more widely in susceptibility to fusidic acid. None of the clinical isolates tested was found to be resistant to lysostaphin.
Ampicillin↗
Successful treatment of MRSA otorrhoea: a case report.
Infection with methicillin-resistant Staphylococcus aureus (MRSA) is increasing. It may be community or hospital acquired and is characteristically difficult to eradicate. Here we report a case of a two-year-old girl who sustained a traumatic tympanic membrane perforation following a minor burns injury. She was seen as an out-patient in a burns unit and subsequently developed MRSA otorrhoea. This was treated with a two-week course of fusidic acid topical drops. At three-week follow up the tympanic membrane had healed and the infection had healed completely. Fusidic acid is safe and effective in the treatment of MRSA otorrhoea. We need to maintain vigilance in the treatment of otorrhoea, as MRSA may become an increasingly common pathogen in the future.
Administration, Topical↗