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PubMed1997

Successful management of an infected implantable cardioverter defibrillator with oral antibiotics and without removal of the device.

Infection of an implantable cardioverter defibrillator developed 2 weeks after implantation, presenting with fever, swelling, redness, and tenderness of the skin above the generator site. A cloxacillin resistant coagulase-negative staphylococcus was repeatedly cultured from the abdominal wall pocket fluid. The infection was successfully treated with a combination of two antibiotics, fusidic acid and rifampin, given orally for 3 months. Although the device was not removed, infection did not recur during a 24-month follow-up.

Administration, Oral↗
PubMed1994

Is Escherichia coli ATCC 25922 a colicin producing strain? (a note).

The well-characterized strain of Escherichia coli ATCC 25922 recommended and widely used as a control Gram-negative bacterium for various laboratory experiments, especially for antibiotic susceptibility assays, was found to be antagonistic against another E. coli strain which is uniquely susceptible to fusidic acid, an antibiotic mainly active against Gram-positive bacteria. This antagonistic property appears to be selective, since it was not found against other E. coli or Staphylococcus aureus strains.

Bacteriological Techniques↗
PubMed2006

Multiple combination bactericidal testing of staphylococcal biofilms from implant-associated infections.

Standardized susceptibility testing fails to predict in vivo resistance of device-related infections to antimicrobials. We assessed agents and combinations of antimicrobials against clinical isolates of Staphylococcus epidermidis and S. aureus (methicillin-resistant S. aureus and methicillin-sensitive S. aureus) retrieved from device-associated infections. Isolates were grown planktonically and as biofilms. Biofilm cultures of the organisms were found to be much more resistant to inhibitory and bactericidal effects of single and combination antibiotics than planktonic cultures (P < 0.001). Rifampin was the most common constituent of antibiotic combinations active against staphylococcal biofilms. Other frequently effective antimicrobials were vancomycin and fusidic acid. Susceptibility testing involving biofilm-associated bacteria suggests new options for combination antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1999

Role of the alkyl hydroperoxide reductase (ahpCF) gene in oxidative stress defense of the obligate Anaerobe bacteroides fragilis.

In this study we report the identification and role of the alkyl hydroperoxide reductase (ahp) gene in Bacteroides fragilis. The two components of ahp, ahpC, and ahpF, are organized in an operon, and the deduced amino acid sequences revealed that B. fragilis AhpCF shares approximately 60% identity to orthologues in other gram-positive and gram-negative bacteria. Northern blot hybridization analysis of total RNA showed that the ahpCF genes were transcribed as a polycistronic 2.4-kb mRNA and that ahpC also was present as a 0.6-kb monocistronic mRNA. ahpC and ahpCF mRNAs were induced approximately 60-fold following H(2)O(2) treatment or oxygen exposure of the parent strain but were constitutive in a peroxide-resistant strain. Further investigation using an ahpCF'::beta-xylosidase gene transcriptional fusion confirmed that ahpCF had lost normal regulation in the peroxide-resistant strain compared to the parent. The ahpCF mutant was more sensitive to growth inhibition and mutagenesis by organic peroxides than the parent strain, as determined by disk inhibition assays and the frequency of mutation to fusidic acid resistance. This finding suggests that the ahp genes play an important role in peroxide resistance in B. fragilis. Under anaerobic conditions, we observed increases in the number of spontaneous fusidic acid-resistant mutants of five- and sevenfold in ahpCF and ahpF strain backgrounds, respectively, and eightfold in the ahpCF katB double mutant strain compared to the parent and katB strains. In addition, ahpCF, ahpF, and ahpCF katB mutants were slightly more sensitive to oxygen exposure than the parent strain. Moreover, the isolation of a strain with enhanced aerotolerance and high-level resistance to alkyl hydroperoxides from an ahpCF katB parent suggests that the physiological responses to peroxide toxicity and to the toxic effects of molecular oxygen are overlapping and complex in this obligate anaerobe.

Amino Acid Sequence↗
PubMed1990

Purification and characterization of elongation factor G from bovine liver mitochondria.

The mitochondrial protein synthesis translocase elongation factor Gmt (EF-Gmt) from bovine liver has been purified to greater than 90% homogeneity by a combination of conventional gravity and high performance liquid chromatography. The purification scheme results in an approximate overall 14,000-fold purification with 2% total recovery of EF-Gmt activity. Gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicate that the mitochondrial factor is a single polypeptide with a molecular weight of 80,000. EF-Gmt displays similar levels of activity on its homologous mitochondrial ribosomes and on Escherichia coli ribosomes. The mitochondrial translocase is sensitive to temperatures above 37 degrees C, but the factor is partially protected from heat inactivation in the presence of GTP or GDP. The activity of EF-Gmt is inhibited by treatment of the factor with N-ethylmaleimide. In contrast to all other translocases tested to date, EF-Gmt is completely resistant to the inhibiting effect of fusidic acid when tested on its homologous ribosomes. It displays weak sensitivity to this antibiotic when assayed in the presence of heterologous E. coli ribosomes.

Animals↗
PubMed1990

Outcome after acute osteomyelitis in preterm infants.

Eight cases of skeletal infection in preterm infants were studied. All the infants were systemically unwell, with polymorpholeucocytosis. Diagnosis was by blood culture, and any radiographic changes were apparent at the time of presentation. Infection was often multifocal, with sites around the knee being most commonly affected. Staphylococcus aureus was the pathogen isolated in six of the eight cases; in these treatment with fusidic acid was effective and well tolerated, even at doses that were less than the recommended therapeutic minimum. Even with prompt diagnosis and aggressive treatment orthopaedic sequelae are common.

Acute Disease↗
PubMed1983

[Treatment of burns in childhood].

Management of burns in children depends above all on infusion therapy, i.e. replacement of the plasma, water and electrolytes of which the circulation and tissue have been deprived as a result of exudation into the wound area, increased evaporation of water, and edema. The inexperienced therapist tends to underestimate these losses in the case of children. In infants and older children with burns covering upwards of 5% and 10% respectively of body surface there is a danger of shock developing, with peripheral vasoconstriction, acidosis, cerebral edema and renal failure. Infusion therapy should therefore be instituted as early as possible. Fusidic acid has proved very valuable in topical treatment of burns in children. Concomitant antimicrobial treatment can be dispensed with in the majority of patients. Keloid overgrowths are now more effectively prevented by means of Lycra pressure dressings.

Burns↗
PubMed1985

The in-vitro activity of some antimicrobial agents against methicillin-resistant Staphylococcus aureus.

A total of 185 strains of methicillin resistant Staphylococcus aureus was investigated for sensitivity to five other antimicrobial agents. The vast majority of these strains were also resistant to gentamicin and fusidic acid. Rifampicin was the most active drug tested (MIC90, 0.007 mg/l), while two newer compounds teichomycin and ciprofloxacin showed equal and appreciable activity (MIC90, 0.5 mg/l).

Anti-Bacterial Agents↗
PubMedDate not supplied

In vitro studies of antibiotic sensitivities of Streptomyces somaliensis--a cause of human actinomycetoma.

Ten Streptomyces somaliensis strains isolated from mycetoma patients were tested in vitro against 13 antibacterial agents. Rifampicin was the most effective antibiotic in terms of low minimum inhibitory concentration (MIC) followed by erythromycin, tobramycin, fusidic acid and streptomycin sulphate. The S. somaliensis strains were all resistant to trimethoprim, even though the combination of sulphamethoxazole and trimethoprim is commonly used as treatment.

Actinomycetales Infections↗
PubMed1995

A new mutation in 16S rRNA of Escherichia coli conferring spectinomycin resistance.

We report a novel mutation, C1066U in 16S rRNA which was selected for resistance to spectinomycin, an antibiotic which inhibits ribosomal translocation. The minimal inhibitory concentration (MIC) of spectinomycin determined for this mutant (15 micrograms/ml) is greater than with the wild-type plasmid (5 micrograms/ml) but lower than with the well known C1192U mutation (> 80 micrograms/ml). The C1066U mutation also increases the cells sensitivity to fusidic acid, another antibiotic which inhibits translation at the translocation stage, whereas C1192U is unchanged relative to the wild type. We discuss why the acquisition of resistance to one of these drugs is often associated with hypersensitivity to the other.

Base Sequence↗
PubMed1991

Value of Clostridium difficile antigen test in immunocompromised hosts in the tropics.

39 fecal and body fluid specimens of immunocompromised patients who developed diarrhoea were tested for Clostridium difficile antigen test. The test was identified in only 11 and in one ascitic fluid. Endoscopy was performed in 5 patients and it showed pseudomembranous colitis in one. Numerous antibiotics were associated with C. difficile related diarrhea: ampicillin, 43%; cephalosporins, 43% and clindamycin, 14%. Three Salmonella sp., and one Entamoeba histolytica were detected among patients who later developed C. difficile associated diarrhea. The effect of oral vancomycin and fusidic acid was demonstrated in patients with C. difficile related diarrhea or colitis. The C. difficile antigen test is promising diagnostic tool in immunocompromised hosts in the tropics where both Salmonella and E. histolytica all are endemic.

Anti-Bacterial Agents↗
PubMed2005

Epidural abscess in an obstetric patient with patient-controlled epidural analgesia--a case report.

We present the case of a 37-year-old pregnant woman who underwent a cesarean section due to previous cesarean delivery. Spinal anesthesia was performed at the L2-3 intervertebral space with an epidural catheter inserted at L1-2 for postoperative patient-controlled epidural analgesia. When the epidural catheter was removed on day three, an area of redness round the entry point was noted and the patient complained of low back pain, but was discharged from hospital. Later the same day, she felt backache so severe that she was unable to stand up or bend her body. She called for help and was sent to our emergency room. Physicians noted a small amount of discharge from the insertion site, and the body temperature was elevated to 38 degrees C. An anesthesiologist and an infectious disease specialist were consulted, and an epidural abscess was suspected. Urgent magnetic resonance imaging revealed an epidural abscess at L1-2. After five days of unsuccessful treatment with oxacillin, a 28-day course of vancomycin, followed by two months of oral fusidic acid, resulted in complete remission of the epidural abscess. The patient has remained free of neurologic deficit.

Adult↗
PubMed1997

[Postoperative mediastinitis due to methicillin resistant Staphylococcus epidermidis with low sensitivity to vancomycin].

BACKGROUND: Vancomycin is the drug of choice for methicillin-resistant Staphylococcus. Antibiotherapy failure is rarely clinically related to Staphylococcus with vancomycin low susceptibility. CASE REPORT: A surgical cure of an aortic stenosis in a neonate was complicated by a Staphylococcus mediastinitis. After initiation of antibiotherapy with vancomycin and rifampin and surgical debridement, there was a rapid improvement. Few days later, failure of therapy was obvious. Despite continuous infusion of vancomycin, with a serum level of 29 mg/L, blood cultures were positive again to Staphylococcus. There was no endocarditis or inadequate surgical drainage. Susceptibility of the Staphylococcus was tested, looking for a tolerant strain. The vancomycin minimum bactericidal concentration was 30 mg/L (above usual value 2 to 8 mg/L), while the minimum inhibitory concentration was 3.75 mg/L. A higher dosage of vancomycin associated with fusidic acid was rapidly efficient, and total recovery was achieved. CONCLUSION: In case of failure of vancomycin therapy, despite correct serum levels, the susceptibility of the Staphylococcus strain has to be determined. A low susceptibility strain prescribes more prolonged combination of two antibiotics.

Anti-Bacterial Agents↗
PubMed2000

Inhibition of protein synthesis by didemnin B: how EF-1alpha mediates inhibition of translocation.

The antineoplastic cyclic depsipeptide didemnin B (DB) inhibits protein synthesis in cells and in vitro. The stage at which DB inhibits protein synthesis in cells is not known, although dehydrodidemnin B arrests translation at the stage of polypeptide elongation. Inhibition of protein synthesis by DB in vitro also occurs at the elongation stage, and it was shown previously that DB prevents EF-2-dependent translocation in partial reaction models of protein synthesis. This inhibition of translocation displays an absolute requirement for EF-1alpha; however, the dependence upon EF-1alpha was previously unexplained. It is shown here that DB binds only weakly to EF-1alpha/GTP in solution, but binds to ribosome. EF-1alpha complexes with a dissociation constant K(d) = 4 microM. Thus, the inhibition of protein synthesis by DB appears to involve an interaction with both EF-1alpha and ribosomes in which all three components are required. Using diphtheria toxin-mediated ADP-ribosylation to assay for EF-2, it is demonstrated that DB blocks EF-2 binding to pre-translocative ribosome.EF-1alpha complexes, thus preventing ribosomal translocation. Based on this model for protein synthesis inhibition by DB, and the proposed mechanism of action of fusidic acid, evidence is presented in support of the Grasmuk model for EF-1alpha function in which this elongation factor does not fully depart the ribosome during polypeptide elongation.

Animals↗
PubMed1973

Protein synthesis in vitro in a system from plant mitochondria.

A mitochondrial system from 48h-germinating seeds of Vigna sinensis (Linn.) Savi is capable of incorporating l-[U-(14)C]valine into proteins and is practically insensitve to cycloheximide, but highly sensitive to chloramphenicol and fusidic acid, a potent inhibitor of peptide-chain elongation factor. A system consisting of mitochondrial S-100 fraction and ribosomes from the same source and other cofactors is capable of polyphenylalanine synthesis and behaves similarly with respect to these inhibitors.

Carbon Radioisotopes↗
PubMed1999

Streptococci isolated from various skin lesions: the interaction with Staphylococcus aureus strains.

We isolated 73 streptococcus strains (41 from infections, and 32 from colonization) from various skin diseases between March, 1994, and June, 1998. In 29 out of 41 cases of infective origin, Staphylococcus aureus strains were simultaneously isolated. Twenty-four out of 28 patients with impetigo were suffering from atopic dermatitis. We confirmed that impetigo lesions where Streptococcus pyogenes was dominant in number always showed thick-walled pustules on an erythematous base; these skin lesions were considered to be an early manifestation of streptococcal impetigo. We further confirmed that thick-crusted lesions in streptococcal impetigo, where S. aureus exceeded S. pyogenes in number, were a late manifestation. Antimicrobial agents such as minocycline, fusidic acid, ofloxacin and tosufloxacin, were more effective against S. aureus strains than against beta-hemolytic streptococcal strains. In contrast, ampicillin, cefdinir, imipenem, erythromycin and vancomycin were more effective against beta-hemolytic streptococcal strains.

Ampicillin↗
PubMed1986

Countergradients of nonchemotactic ligands for N-formylmethionylleucylphenylalanine (FMLP) receptors promote FMLP-induced chemotaxis.

Using the under-agarose chemotaxis assay, addition of compounds known to inhibit chemotaxis of leukocytes toward N-f-Met-Leu-Phe (FMLP) was made to the first well in a line of three wells, leukocytes to the middle well, and a slight excess of FMLP to the third well. The compounds included rifampin, fusidic acid, carbobenzoxy Phe-Met, phenylbutazone, sulfinpyrazone, sulfasalazine, and sulfapyridine. The countergradients created in this system markedly stimulated, not inhibited, locomotion toward FMLP. These results, based on functional responses, confirm data using radiolabeled FMLP and support the hypothesis that these compounds are nonchemotactic ligands for FMLP receptors.

Binding, Competitive↗