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[Hydrogel, a new galenic form in ophthalmology].

Good tolerance, long intervals of application and an excellent adhesion are the properties of viscous eye drops (Hydrogels). The use of fusidic acid as a hydrogel in the treatment of bacterial eye infections guarantees a long-lasting antibiotic concentration in tear fluid. When given twice daily, there will be sufficient concentration of the antibiotic in all important tissues of the eye and at the same time it increases the patient compliance.

Eye Diseases↗

Stimulation by aminoacyl-tRNA of the GTPase and ATPase activities of rat liver 5S RNA protein particles in the presence of EF-2.

The GTP- and ATP-hydrolyzing activities of the rat liver 5S RNA-L5 (according to the proposed common nomenclature (1) protein complex designated as 5S RNP were stimulated by pig liver elongation factor 2 (EF-2) plus aminoacyl-tRNA, both of which were required for the stimulation. The stimulative effect of aminoacyl-tRNA on GTP hydrolysis by the complete system containing 5S RNP and EF-2 was dependent on the concentration of aminoacyl-tRNA. Aminoacyl-tRNA also stimulated ATP hydrolysis by the complete system but did not stimulate the ATP hydrolysis by 5S RNP alone or EF-2 alone. While deacylated tRNA stimulated the ATPase activity of the complete system, it had no effect on the GTPase activity. Preincubated tRNA lacking the 3'-terminal CCA moiety had little effect on the GTPase and ATPase activities of the complete system. Fusidic acid inhibited the GTPase and the ATPase activities of the complete system with and without aminoacyl-tRNA, although the extent of the inhibition was larger in the presence of aminoacyl-tRNA. These results suggest that 5S RNP may be a component of the GTPase center of rat liver 60S subunits.

Adenosine Triphosphatases↗

In vitro studies on ppGpp synthetase I from polyamine-starved and unstarved Escherichia coli.

We have studied the in vitro formation of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) using a partially purified ppGpp synthetase I (PSI) from Escherichia coli BGA8, a polyamine auxotrophic strain. A comparison of the enzyme obtained from polyamine-supplemented or deprived bacteria showed similar requirements for the reaction, Mg+2 optimum levels and sparing effect of spermidine. No differences in the inhibitory effects of tetracycline, puromycin and fusidic acid were detected either. However, a modified subcellular distribution, as well as a larger specific activity and a larger stimulation by streptomycin was observed when PSI was prepared from polyamine-depleted bacteria. The role of ribosome assembly and subunit distribution on the altered properties of the enzyme are discussed.

Anti-Bacterial Agents↗

Comparative inhibition of methicillin-resistant strains of Staphylococcus aureus by lysostaphin and other antibiotics.

Sixteen methicillin-resistant strains of Staphylococcus aureus obtained from Europe were found to be sensitive to the lytic activity of lysotaphin. With only minor exceptions, the strains were found to be sensitive to novobiocin, erythromycin, fusidic acid, and lincomycin, and slightly less sensitive to vancomycin and chloramphenicol. All strains were resistant to tetracycline, penicillinase-sensitive penicillins (benzylpenicillin, ampicillin, and propicillin), penicillinase-resistant penicillins (methicillin, nafcillin, ancillin, oxacillin, cloxacillin, and dicloxacillin), and two cephalosporin antibiotics (cephalothin and cephaloridine).

Anti-Bacterial Agents↗

A translocation-associated ribosomal conformational change detected by hydrogen exchange and sedimentation velocity.

Translocation in ribosomes consists of transposition of peptidyl-tRNA from the aminoacyl to the peptidyl site and, probably concomitantly, the movement of ribosomes on mRNA. Does a conformational change in the ribosome provide the motive force for this process? Hydrogen exchange and sedimentation velocity experiments indicate that the Escherichia coli ribosome does undergo a conformational change associated with translocation. When pretranslocational ribosomes carrying acetyldiphenylalanyl-tRNA in the aminoacyl site were incubated with G factor and GTP, translocation occurred, with a concomitant increase in hydrogen exchange rate and a decrease in sedimentation constant. These changes did not occur when GTP was replaced by a nonhydrolyzable analogue, GDP-CH(2)-P, and they were blocked by the antibiotics fusidic acid and thiostrepton. When posttranslocational ribosomes were cycled back to the pretranslocational state by T factor, GTP, and phenylalanyl-tRNA, the sedimentation constant reverted to the original value. Whether or not this conformation change drives translocation requires further study.

Anti-Bacterial Agents↗

Antibiotics and human monocyte function. I. Chemotaxis.

The influence of thirteen commonly used antibacterial drugs on the chemotactic responsiveness of human blood monocytes in vitro was investigated. Tetracyklin, trimethoprim and fusidic acid at high concentrations produced a significant inhibition of the monocyte response, whereas normal therapeutic concentrations produced insignificant inhibition. Benzylpenicillin, ampicillin, tobramycin, chloramphenicol, metronidazole, rifampicin, clindamycin, sulfametoxazole, cefotaxime and ofloxacin did not alter monocyte migration. From these observations it can be expected that at normal dosages none of the tested drugs will affect monocyte chemotaxis in vivo.

Adult↗

[Nasal carriage of Staphylococcus aureus in hospital personnel and the normal population and antibiotic resistance of the isolates].

Nasal carriage of Staphylococcus aureus plays a key role in the epidemiology and pathogenesis of infection, and is a major risk factor for the development of both community-acquired and nosocomial infections. The objective of this study was to investigate the carriage rate of S. aureus in hospital personnel and normal population groups, and to compare the resistance rates of the isolated strains to certain antibiotics. The nasal carriage rates of S.aureus were found to be 27.5% in 262 hospital personnel, and 24.0% in 75 normal healthy subjects (p > 0.05). While methicillin resistant S. aureus rate was 9.7% in hospital personnel, no methicillin resistant strain was detected in the control group (p < 0.05). According to the in-vitro sensitivity test results, resistance rates of meticillin sensitive S. aureus (MSSA) strains isolated from hospital personnel to fusidic acid, erythromycin and clindamycin were as 11%, 18% and 12%, respectively. There were no resistant strains to these antibiotics among MSSA, isolated from normal subjects. In conclusion, the colonization of the resistant strains rather than the frequency of S. aureus colonization is more important in the hospital personnel.

Anti-Bacterial Agents↗

Mapping of the resistance genes of the R plasmid NR1.

The drug resistance genes on the r-determinants component of the composite R plasmid NR1 were mapped on the EcoRI restriction endonuclease fragments of the R plasmid by cloning the fragments using the plasmid RSF2124 as a vector. The sulfonamide (Su) and streptomycin/spectinomycin (Sm/Sp) resistance genes are located on EcoRI fragment G of NR1. The expression of resistance to mercuric ions (Mer) requires both EcoRI fragment H and I of NR1. The expression of chloramphenicol (Cm) and fusidic acid (Fus) resistance requires EcoRI fragments A and J of NR1. The kan fragment of the related R plasmid R6-5 can substitute for Eco RI fragment J of NR1 in the expression of Cm and Fus resistance. The structural genes for Cm and Fus resistance appear to be a part of an operon whose expression is controlled by the same promoter.

Chloramphenicol↗

[The control leprous peripheral neuropathy and chemotherapy].

Clarithromycin(CAM), Roxithromycin(RXM), Minocycline(MINO) and Fosfomycin(FOM) has anti-inflammatory action and immunomodulatory activity, while the anti-mycobacterium leprae activity is shown. CAM and RXM suppress the rat carrageenin edema, and MINO suppresses the rat adjvant arthritis. There is the immunosuppression on adrenocorticosteroid while the inflammatory cytokine is suppressed. CAM, MINO, FOM suppresses the inflammatory cytokine, while it has the immunomodulatory activity. Fusidic acid(FA) suppresses the inflammatory cytokine with the action of being similar to cyclosporin A, and it has the immunomodulatory activity. New macrolides derivatives, CAM and RXM showed the inflammatory regulation, and MINO showed the anti-inflammatory activity with FA. The combination chemotherapy can be enforced, while peripheral neuropathy is prevented by the control of the leprosy reaction.

Adjuvants, Immunologic↗

MRSA eradication in a health care worker with cystic fibrosis; re-emergence or re-infection?

Methicillin-resistant Staphylocosis aureus (MRSA) is an emerging infection in patients with cystic fibrosis (CF). MRSA may be a management dilemma for healthcare workers (HCWs) with CF. Eradication of MRSA with long-term rifampicin and fusidic acid can be achieved in patients with CF. We describe a case of recurrent MRSA infection in a HCW with CF. Molecular typing of the MRSA isolates supported re-infection rather than re-emergence of an earlier MRSA infection. Infection control advice for HCWs with CF who acquire MRSA remains controversial.

Adult↗

Ribosomes cannot interact simultaneously with elongation factors EF Tu and EF G.

Prior binding of EF G and GDP to 70S ribosomes from Escherichia coli prevents the subsequent binding of aminoacyl-tRNA, mediated by EF Tu. However, the interaction of EF Tu.GTP.aminoacyl-tRNA with the 30S subunit, which results in aminoacyl-tRNA binding without GTP hydrolysis, appears to be unaffected by EF G, GDP, and fusidic acid. We conclude that elongation factors Tu and G cannot interact simultaneously with the ribosome. The simplest interpretation of these and earlier data is that EF G and EF Tu interact with the same, or overlapping, 50S ribosomal sites in the course of GTP hydrolysis associated with translocation and aminoacyl-tRNA binding, respectively. In any event, these factors must alternate in binding to the ribosome in the course of each elongation cycle.

Escherichia coli↗

Confocal laser scanning microscopic observation of glycocalyx production by Staphylococcus aureus in mouse skin: does S. aureus generally produce a biofilm on damaged skin?

BACKGROUND: Bacteria that adhere to damaged tissues encase themselves in a hydrated matrix of polysaccharides, forming a slimy layer known as a biofilm. This is the first report of detection of glycocalyx production by Staphylococcus aureus using confocal laser scanning microscopy (CLSM) on damaged skin tissues. OBJECTIVES: To analyse glycocalyx production by S. aureus cells on damaged skin tissues and the influence of polymorphonuclear leucocytes (PMNs) and various antimicrobial agents on its production using CLSM in cyclophosphamide (Cy)-treated (neutropenic) or non-Cy-treated (normal) mice. METHODS: S. aureus cells were inoculated on damaged skin tissues in neutropenic or normal mice with or without topical application of antimicrobial agents. S. aureus cells were stained with safranine, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested on damaged skin tissues formed microcolonies encircled by glycocalyx. The colony counts of S. aureus cells on croton oil dermatitis in normal mice treated with 2% fusidic acid ointment were about 100 times lower than those in neutropenic mice (control). CONCLUSIONS: As S. aureus cells can generally produce a biofilm on damaged skin tissues, antimicrobial agents may not eradicate S. aureus cells without the help of PMNs. S. aureus glycocalyx may play a crucial role in colonization and adherence to damaged skin tissues.

Animals↗

Novel mutants of elongation factor G.

A novel mutant form of elongation factor G (EF-G) in Escherichia coli is described. This variant EF-G restricts reading frame errors by a factor of 2 to 3 in vivo at two different positions in a lacIZ fusion. In addition, a conventional fusidic acid resistant (fusR) mutant of EF-G was compared with the restrictive mutant. Both mutants were characterized in vitro in a steady-state poly(U) translating system. The data indicate that the restrictive EF-G variant has an altered interaction with the ribosome both in vivo and in vitro. In contrast, the conventional fusR variant is altered in its interaction with GTP, which is evident in vitro.

Drug Resistance, Microbial↗

A systematic review and meta-analysis of treatments for impetigo.

BACKGROUND: Impetigo is a common clinical problem seen in general practice. Uncertainty exists as to the most effective treatment, or indeed if treatment is necessary. AIM: To determine the most effective treatment for impetigo in a systemically well patient. DESIGN OF STUDY: Systematic review and meta-analysis. METHOD: Databases were searched for relevant studies. The Cochrane highly sensitive randomised controlled trial (RCT) search string was employed and combined with the word 'impetigo' as the MeSH term and keyword. The bibliographies of relevant articles were searched for additional references. RCTs that were either double- or observer-blind, and involved systemically well patients of any age in either primary or secondary care settings, were included. Studies that selected patients on the basis of skin swab results were excluded, as were studies that were not in English. Cure or improvement of impetigo reported at seven to 14 days from start of treatment was the primary outcome measure. Meta-analysis was performed on homogeneous studies. RESULTS: Three hundred and fifty-nine studies were identified, of which 16 met the inclusion criteria. Meta-analysis demonstrated that topical antibiotics are more effective than placebo (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.49 to 4.86). There is weak evidence for the superiority of topical antibiotics over some oral antibiotics, such as erythromycin (OR = 0.48, 95% CI = 0.23 to 1.00). There is no significant difference between the effects of mupirocin and fusidic acid (OR = 1.76, 95% CI = 0.77 to 4.03). CONCLUSION: This review found limited high-quality evidence to inform the treatment of impetigo. From that which is available, we would recommend the use of a topical antibiotic for a period of seven days in a systemically well patient with limited disease. Further research is needed on the role of flucloxacillin and non-antibiotic treatments for impetigo.

Administration, Topical↗

Acute haematogenous osteomyelitis.

Seventy-seven children admitted with a provisional diagnosis of acute osteomyelitis over a three year period have been reviewed. Acute haematogenous osteomyelitis was confirmed in 45 of these patients whose ages varied from three days to 14 years with a mean of 6.2 years. All patients were treated with intravenous fusidic acid and cloxacillin with splintage for three weeks followed by oral antibiotics for a further period of six weeks. Only seven patients required operation. One patient had recurrence of infection; all other patients were cured with no evidence of chronic osteomyelitis. It is suggested that surgical drainage of acute haematogenous osteomyelitis is seldom needed and that high intravenous doses of antibiotics in combination with splintage are adequate treatment in most cases.

Acute Disease↗

[A patient with acute leukemia and meningitis caused by Staphylococcus epidermidis treated with fosfomycin].

In a 17-year-old male patient with acute lymphoblastic leukaemia, who was being treated with chemotherapy, a Staphylococcus epidermidis infection with several septicaemias developed during a period of protracted neutropenia. The patient was treated with vancomycin and fusidic acid, but blood cultures remained positive. The patient also developed staphylococcal meningitis. After the antibiotic regimen was supplemented by fosfomycin, the blood cultures became sterile. Combination treatment with vancomycin and fosfomycin was continued for two months without apparent toxicity. In individual cases of infection with multiresistant S. epidermidis fosfomycin may be included in the antibiotic regimen. This is the first report of parenteral use of fosfomycin in the Netherlands.

Adolescent↗

In vitro activity of six antibiotics against multiresistant staphylococci and other gram-positive cocci.

Sixty-two strains of Staphylococcus aureus and coagulase-negative staphylococci, 21 Streptococcus faecalis and 17 other strains of streptococci isolated from cases of endocarditis were tested for sensitivity against rifampicin, teicoplanin, vancomycin, fusidic acid, erythromycin and novobiocin. Only rifampicin, novobiocin and teicoplanin were found to be active against the great majority of these strains. The microbial properties of these antibiotics suggest the necessity of combinations for effective therapy. The combinations rifampicin + novobiocin and rifampicin + teicoplanin were additive and suppressed the emergence of resistant mutants. Thus according to in vitro tests, either of these two combinations would be suitable for prophylactic use in high-risk patients, especially those scheduled to receive prosthetic implants.

Anti-Bacterial Agents↗

[Combination of novoimanine with antibiotics with a different mechanism of action].

Ampicillin, kanamycin, fusidic acid and rifocin significantly increased the effect of novoimanin on Staph. aureus 209. Histon F1 and spectinomycin did not influence the effect of novoimanin. Inefficiency of novoimanin combination with histon F1 provided a supposition that their effect may be directed to the same cell structures and most probably to the membranes. This was confirmed by the data of electron microscopy. The most effective combinations were recommended for the studies on their possible clinical use.

Ampicillin↗