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[Mapping the fucidin resistance marker in S. typhimurium and a study of the properties of its transductants].

The fusidic resistance marker in S. typhimurium is contransduced in 95% of cases by means of P 22 phage with the streptomycin resistance marker. The transfer of the fusidic acid resistance gene doesn't lead to any significant alterations in the tranductants' properties (morphology, antigenic structure, growth rate, biochemical activity, sensitivity to other antibiotics). The fusidic acid resistant mutants and transductants studied displayed a significantly decreased virulence to albino mice. The rate of this decrease, however, doesn't correspond to the degree of transductants' resistance. Virulent variants are also possible.

Animals↗

Alternative delivery of insulin via eye drops.

BACKGROUND: Various insulin delivery systems have been considered for systemic absorption other than injections. Although the ocular route has been suggested, its use is limited by the amount of insulin absorbed systemically via eyes. In order to improve the absorption rate of insulin into systemic circulations, the effects of pH and absorption enhancers were studied with rabbit eyes. METHODS: Insulin eye drops were instilled into eyes of rabbits, and their blood glucose levels were measured with a Glucoscan 200 Meter (Lifescan, Mountain View, CA). RESULTS: Systemic absorption of insulin via the ocular route was much more prominent at higher pH (8.0) than at lower pH (3.5). When absorption enhancers such as glycocholate and fusidic acid were added, the insulin absorption increased further markedly. CONCLUSION: It is feasible to administer insulin through the eyes at pH 8.0 with low concentrations of glycocholate or fusidic acid to achieve the therapeutic efficacy of insulin to lower blood glucose to normal levels.

Absorption↗

Antimicrobial susceptibility pattern of Clostridium difficile and its relation to PCR ribotypes in a Swedish university hospital.

All 238 Clostridium difficile isolates were susceptible to metronidazole and vancomycin, whereas 84% and 1% were resistant to clindamycin and fusidic acid. Etest MICs for metronidazole were lower than agar dilution MICs (P < 0.01) but without difference in susceptible-intermediate-resistant categorization. No particular PCR ribotype was associated with clindamycin or fusidic acid resistance.

Anti-Bacterial Agents↗

[Evaluation of the efficacy and toxicity of local fusidic aid versus oral dicloxacillin in infections of the skin].

In a double-blind test it was shown the efficacy of topical fusidic acid in comparison with oral dicloxacillin, in patients with skin infection by Staphylococcus aureus or/and Streptococcus pyogenes. In the experimental group, 16 patients from 20 received 2% topical fusidic acid in cream and reacted well in a shorter period of time than 17 from a group of 20 that had 500 mg. of dicloxacillin orally twice a day.

Administration, Oral↗

The disposition of sodium fusidate in man.

1 In a pharmacokinetic study in six volunteers serum fusidic acid concentrations were obtained after rapid intravenous administration of 100 mg. 2 Analysis of the data suggests that the serum concentration/time curve is biphasic and that the curve can be described by the following equation: cp=5.9e(-1.82t)+4.3e(-0.13t). 3 The disposition characteristics of sodium fusidate have been calculated from this relationship and a plasma half life for sodium fusidate of between 5 and 6 h obtained. 4 Subsequently plasma fusidic acid levels have been measured in the same volunteers on three occasions after sodium fusidate (500 mg) given either as a slow intravenous infusion, or orally as a capsule or as a suspension. 5 Serum levels and AUC after a capsule were about 75% of those obtained after the infusion (30 and 70 mg/1 at peak respectively) whereas levels and AUC after the suspension were only about 50%.

Adult↗

Characterization of ATP-dependent proton transport in medullary bone-derived microsomes.

Proton transport in microsomal vesicles derived from medullary bone of laying hens was observed to be inhibited in a dose-dependent manner with fusidic acid, 7-chloro-4-nitrobenz-2-oxa-1,3-diatzole (NBD-Cl), duramycin and dicyclohexylcarbodiimide (DCCD). The IC50 values were 570 microM, 4.5 microM, 10 micrograms/ml and 32 microM for fusidic acid, NBD-Cl, duramycin and DCCD, respectively. 14C-DCCD labeled a single protein band of 15-17 kDa from bone-derived microsomes in SDS-electrophoresis. A protein of this size is a proton-conducting subunit of the vacuolar ATPases. Further, the proton transport was found to be electrogenic, thus it generates the membrane potential across the vesicle membrane. The generation of membrane potential was inhibited using 100 nM bafilomycin A1, which in low concentrations is a specific inhibitor of vacuolar ATPases. The presence of Cl- was essential for maximal proton transport activity. These results confirm the electrogenicity and extend the characterization of the osteoclastic H(+)-ATPase.

Adenosine Triphosphate↗

In vitro activity of ceftazidime in combination with other antibiotics.

189 bacterial strains were investigated for their in vitro sensitivity against ceftazidime (alone and in combination with another antibiotic). Moreover, the possibility to prevent development of secondary bacterial resistance as observed in subcultures at subinhibitory antibiotic concentrations, was studied using specific antibiotic combinations. Of 115 staphylococcal strains (91 strains of Staphylococcus aureus, 24 strains of Staphylococcus epidermidis), 2% were sensitive, 82% were moderately sensitive and 16% were resistant to ceftazidime. On combining ceftazidime with vancomycin, synergism was found in 61% of the strains, and secondary resistance to ceftazidime could be prevented with this combination. The combination of ceftazidime and clindamycin showed synergism in 26% and an additive effect in 48% of the strains. Secondary resistance to ceftazidime did not develop with this combination in subcultures at subinhibitory concentrations in which loss of activity was only minimal with clindamycin alone. Rifampicin and fusidic acid were highly active against staphylococci. In combination with ceftazidime, only weak synergism or additive effects were seen in most strains; no antagonism could be observed. In subcultures at subinhibitory concentrations, secondary resistance to rifampicin and fusidic acid developed rapidly and could be partially prevented by adding ceftazidime. Of 60 Pseudomonas aeruginosa strains, 84% were sensitive, 13% were moderately sensitive and 2% were resistant to ceftazidime. Synergism was most frequently observed when ceftazidime was combined with tobramycin. Using this combination, secondary resistance of Pseudomonas strains to ceftazidime did not develop. When ceftazidime was combined with piperacillin, synergism was observed in most strains, but the development of secondary resistance in vitro was not prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

The clinical efficacy of topical and systemic therapy for the treatment of feline ocular chlamydiosis.

Twenty-four specific-pathogen-free-derived cats aged four to 11 months were challenged by ocular application of a field isolate of Chlamydia psittaci to evaluate the effect of topical and systemic therapy on the course of disease. The cats were monitored for 35 days post-challenge, with severity of clinical signs being measured using a scoring system, and ocular shedding of the organism monitored by culture of conjunctival swabs. All cats developed active C psittaci infection, and after 7 days the cats were randomly assigned to one of four treatment groups: Group P (placebo) was given twice-daily ophthalmic tear-replacement ointment; group F was given twice-daily topical 1% fusidic acid ophthalmic viscous drops; group C was given twice-daily topical 1% chlortetracycline ophthalmic ointment; and group D was given doxycycline at 10 mg/kg daily per os in addition to twice-daily topical 1% fusidic acid ophthalmic ointment. Within 24 h of commencement of therapy, group D had significantly lower median clinical scores than group P, and with the exception of day 16, this trend was maintained throughout the observation period. Median clinical scores of cats in group F were not appreciably different to those in group P, whereas the median scores of cats in group C generally fell between those of groups P and D. The median duration of C psittaci shedding was 10 and 15 days for groups D and C respectively, but four of the six cats in groups F and P were still shedding organisms at the end of the study (day 35). In this study, systemic therapy with doxycycline proved superior to topical therapy in the treatment of feline chlamydiosis.

Administration, Oral↗

Comparative trial of fucidin ointment and fucidin cream in skin sepsis.

A study has been conducted on 101 patients with superficial skin sepsis comparing the effectiveness of topical treatment with 2% sodium fusidate ointment and a new preparation containing 2% fusidic acid in a cream base. The results showed that both topical preparations were equally effective in terms of the number of days for healing to take place and in the subjective assessment of the clinical response. Bacteriological investigation of the swabs from ninety-one patients showed Staphylococcus aureus to be the most frequently isolated pathogen. Both preparations were well tolerated and no adverse reactions were observed. It is suggested that the new 2% fusidic acid cream is particularly suitable for use on lesions requiring no dry dressing, whereas the 2% sodium fusidate ointment is preferred for those conditions where a dressing is applied.

Adolescent↗

Antimicrobial susceptibility of environmental Staphylococcus aureus strains isolated from a pigeon slaughterhouse in Italy.

No information is available concerning the antimicrobial susceptibility of Staphylococcus aureus isolated from pigeon slaughterhouses. In the present study, 59 staphylococcal strains isolated from a pigeon slaughterhouse in central Italy were compared according to their antibiotic resistance. On the basis of cultural and biochemical properties, all isolates could be identified as S. aureus. The strains were checked for the productions of enterotoxins A, B, C, D by reversed passive latex agglutination. Resistance to 26 antibiotics was also determined paying particular attention to resistance to those antimicrobial agents frequently used in human medicine and in poultry breeding. Only one strain was positive for the production of enterotoxins type C and D. It was isolated from the evisceration tube after slaughtering. Enterotoxin B was produced by 2 strains isolated from the eyebrows and conjunctivas of the worker operating the crop rinsing tube. As to the susceptibility to antibiotics, all strains were sensitive to amoxicillin/clavulanic acid, bacitracin, cephalothin, fusidic acid, gentamicin, kanamycin, linezolid, oxacillin, quinupristin/dalfopristin, rifampicin, tobramycin, trimethoprim-sulfamethoxazole, vancomycin. Some (15.2%) of the strains were resistant to ampicillin and to penicillin G; 6.8% were resistant to chloramphenicol, 20.3% to enrofloxacin, 16.9% to erythromycin and to ciprofloxacin, 8.5% to clindamycin, and 11.9% to lincomycin. The highest percentages of strains were resistant to tetracycline and oleandomicin (37.3 and 25.4% respectively). Methicillin-resistant staphylococci were also found (3.4%). Only one strain had a multiple antibiotic resistance index > 0.30. The results were statistically analyzed and clustered in 6 groups. This work provides the antibiotic resistance pattern of S. aureus strains isolated from a pigeon slaughtering plant and represents a study on a quite unknown field in meat production.

Abattoirs↗

Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominantly by two large periplasmic loops.

AcrAB-TolC is a constitutively expressed, tripartite efflux transporter complex that functions as the primary resistance mechanism to lipophilic drugs, dyes, detergents, and bile acids in Escherichia coli. TolC is an outer membrane channel, and AcrA is an elongated lipoprotein that is hypothesized to span the periplasm and coordinate efflux of such substrates by AcrB and TolC. AcrD is an efflux transporter of E. coli that provides resistance to aminoglycosides as well as to a limited range of amphiphilic agents, such as bile acids, novobiocin, and fusidic acid. AcrB and AcrD belong to the resistance nodulation division superfamily and share a similar topology, which includes a pair of large periplasmic loops containing more than 300 amino acid residues each. We used this knowledge to test several plasmid-encoded chimeric constructs of acrD and acrB for substrate specificity in a marR1 DeltaacrB DeltaacrD host. AcrD chimeras were constructed in which the large, periplasmic loops between transmembrane domains 1 and 2 and 7 and 8 were replaced with the corresponding loops of AcrB. Such constructs provided resistance to AcrB substrates at levels similar to native AcrB. Conversely, AcrB chimeras containing both loops of AcrD conferred resistance only to the typical substrates of AcrD. These results cannot be explained by simply assuming that AcrD, not hitherto known to interact with AcrA, acquired this ability by the introduction of the loop regions of AcrB, because (i) both AcrD and AcrA were found, in this study, to be required for the efflux of amphiphilic substrates, and (ii) chemical cross-linking in intact cells efficiently produced complexes between AcrD and AcrA. Since AcrD can already interact with AcrA, the alterations in substrate range accompanying the exchange of loop regions can only mean that substrate recognition (and presumably binding) is determined largely by the two periplasmic loops.

Anti-Bacterial Agents↗

Emergence of a new community acquired MRSA strain in Germany.

Analysis of community-acquired methicillin-resistant Staphylococcus aureus (c-MRSA) from Germany producing the Panton-Valentine leukocidin revealed a unique SmaI-macrorestriction pattern, different from epidemic nosocomial strains. This molecular pattern corresponds to those shown in c-MRSA strains from other countries in the European Union. All isolates exhibited resistance to fusidic acid, which is coded by the far-1 gene. From data on geographical dissemination and time of occurrence, this strain appears to have emerged in Germany in the second half of 2002, and so an already wider dissemination is likely. The emergence of MRSA with resistance to fusidic acid is a first sign of the emergence of a PVL-positive MRSA clone.

Anti-Bacterial Agents↗

The post-antibiotic effect of teicoplanin: monotherapy and combination studies.

The post-antibiotic effect (PAE) of teicoplanin was measured alone and in combination with other antibiotics against Staphylococcus aureus. A total of five strains were used: the Oxford S. aureus and two clinical isolates each of methicillin sensitive and methicillin resistant strains. Fusidic acid had no or a small post-antibiotic influence (range 0-1.25 h) whereas a relatively higher PAE was seen for all other drugs against all strains: teicoplanin 2.4-4.1 h: gentamicin 3.1-5.2 h, rifampicin 3.0-3.95 h, and ciprofloxacin 1.6-3.4 h. Combination of teicoplanin with fusidic acid resulted in shorter PAEs than teicoplanin alone. In contrast, PAEs for all other combinations with teicoplanin were longer than PAE of teicoplanin, gentamicin, rifampicin or ciprofloxacin alone. Addition of teicoplanin during the post-antibiotic phase of the other antibiotics and vice versa showed that the only combination which was consistently bactericidal was that of teicoplanin with gentamicin. We conclude that these in-vitro results suggest that the combination of teicoplanin with gentamicin is likely to be the most effective of those tested and should be further evaluated in clinical trials.

Anti-Bacterial Agents↗

Streptococcus faecalis: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood.

Ampicillin, fusidic acid, gentamicin, imipenem, mezlocillin, ofloxacin, penicillin G, piperacillin, and vancomycin were examined for inhibitory and bactericidal activity in various broth media against 7 clinical isolates of Streptococcus faecalis. On a weight-for-weight basis, ampicillin, imipenem, mezlocillin, and ofloxacin proved to be more efficacious. All enterococcal isolates were resistant against gentamicin; fusidic acid and vancomycin lacked bactericidal activity. The combinations of either ampicillin, imipenem, mezlocillin, ofloxacin, piperacillin, or vancomycin with a subinhibitory concentration (4 micrograms/ml) of gentamicin, with or without added 65% (v/v) fresh defibrinated human blood, respectively, yielded additive effects against all enterococcal isolates. The addition of fresh human blood failed to enhance the antienterococcal activity of 4 micrograms/ml of gentamicin; in contrast, addition of 65% (v/v) fresh or heat-inactivated (56 degrees C, 30 min) normal rabbit, bovine, and human sera augmented the activity of gentamicin, an effect that was ablated through the addition of either 0.005 M DTT or 0.01 M MgCl2 + 0.01 M EGTA + 0.01 M CaCl2, supplements known to antagonize human serum beta-lysin, but not lysozyme activity.

Animals↗

Acquisition of antibiotic resistance by Staphylococcus aureus in skin patients.

Acquisition of resistance to neomycin, gentamicin, fusidic acid, or clindamycin has been observed in three strains of Staphylococcus aureus and data from three patients infected with these strains are presented in detail. Clindamycin resistance followed the expected pattern by appearing in a strain of Staph. aureus with dissociated resistance to erythromycin after treatment with erythromycin and clindamycin. Low-level resistance to fusidic acid appeared in two strains in the apparent absence of exposure to that antibiotic. Labile neomycin resistance was encountered in a previously sensitive strain after topical neomycin therapy. Gentamicin resistance appeared in all three strains after topical therapy. In all three strains, a labile resistance (presumably plasmid-mediated) occurred with minimum inhibitory concentrations (MICs) of 64-128 microgram/ml but in one strain a stable resistance with MIC over 3000 microgram/ml appeared.

Anti-Bacterial Agents↗

[Study of mutants of Salmonella typhimurium with altered sensitivity to the antibiotic fusidin].

S. typhimurium mutants with altered sensitivity to fusidic acid (more resistant or more sensitive than the original culture) were selected. The mutants studied changed some of their properties (morphology, antigenic structure, and biochemical activity). They were characterized by a lower growth rate and probably by some alterations in the envelope cell structures- Some mutants acquired cross resistance or sensitivity to other antibiotics. As the mutants were selected by increased resistance or sensitivity to fusidic acid which affected the translocation factor G of the ribosome cycle, such pleiotropic changes of their properties could be due to some alterations in the G-factor itself.

Drug Resistance, Microbial↗

[An epidemic of bullous impetigo in the municipality of Austevoll in the year 2002].

BACKGROUND: Rising numbers of bullous impetigo caused by Staphylococcus aureus resistant to fucidic acid have been seen in Norway over the last few years. MATERIAL AND METHODS: We present a population-based cohort study of an epidemic in an island community in western Norway with approximately 4450 people. The district's doctors agreed upon guidelines for regimes of antibiotic treatment; taking specimens for bacteriological examination was made routine procedure. The patients included in the study were identified from all patient files from all consultations with all doctors in the district. Clinical, therapeutical and bacteriological variables were registered. A comparison with the present Norwegian guidelines developed by a conference of experts is made. RESULTS: 108 patients were diagnosed as having bullous impetigo (2.4% of the population). Bacteriological swabs were taken from 95 (88%) patients. Staphylococcus aureuswas the bacteriologic aetiology in 79 (83%) of these and were found to be resistant to fusidic acid in 67 (85%) isolates. DISCUSSION: Our findings support the hypothesis that the rising numbers of impetigo might be caused by a clone of Staphylococcus aureus that is resistant to fusidic acid.

Adolescent↗

Static and dynamic properties of tissue cage fluid in rabbits.

The properties of tissue cage fluid in a steel net tissue cage model in rabbits were compared to those of serum by determination of the protein profile, the cell contents, and the pharmacokinetics of 125I albumin, 3H sucrose and 3H fusidic acid. The dominating serum proteins demonstrated by crossed immunoelectrophoresis were also detected in tissue cage fluid but at lower levels and at various ratios. The cell pattern gradually changed from an initial dominance of polymorphonuclear cells to lymphocytes during the five weeks following the subcutaneous implantation of the cages. The distribution of the highly protein-bound fusidic acid was markedly slower and the maximal tissue cage fluid level significantly lower than that of sucrose. Equilibrium of 125I albumin between serum and tissue cage fluid was slowly achieved during the following two weeks. The advantages and disadvantages of tissue cage models for studies of drug pharmacokinetics are discussed. The properties of tissue cage fluid and the possibility of repeated sampling make the model suitable for studies of experimental local infections. The influence of therapeutic agents and the host's response to the infectious process may also be elucidated.

Albumins↗