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The temperature sensitive mutant 72c. I. Pleiotropic growth behaviour and changed response to some antibiotics and mutations in the transcription or translation apparatus.

The spontaneous temperature sensitive mutant 72c is shown to be more tolerant to fusidic acid, but less tolerant to trimethoprim on plates at permissive temperature, than is the parental strain. The poor growth of the mutant on amino acids supplemented plates, as well as its inability to grow on broth plates at 40 degrees, can be compensates by sublethal amounts of chloroamphenicol. Also some mutations to Rif-R or Str-R improve growth of the mutant under certain conditions. Reversion and other genetic analysis strongly suggest, that the pleiotropic behaviour of the mutant is due to a single mutation in a gene, which is designated fusB and is closely cotransducible with lip at min 14 of the E. coli chromosome. The gene order is lip-fusB-supE.

Chloramphenicol↗

Antibiotic sensitivity and phage typing of Staphylococcus aureus isolated from non-hospitalized patients with angular cheilitis.

Strains of Staphylococcus aureus were isolated from 360 patients with angular cheilitis. Of these 24 per cent were sensitive to penicillin G, 74 per cent to tetracycline, 93 per cent to fusidic acid and 96 per cent to erythromycin. Twenty per cent belonged to bacteriophage Group I, 9 per cent to Group II, 13 per cent to Group III, 39 percent miscellaneous and 19 per cent were untypable. A number of phage typing patterns which have been reported for strains associated with specific forms of staphylococcal disease were present in the 360 isolates. In investigations involving cross infection of Staph. aureus, both patients and staff should be examined for evidence of infection at the angles of the mouth.

Anti-Bacterial Agents↗

The treatment of Staphyloccocus aureus infected sore nipples: a randomized comparative study.

Sore, cracked nipples are commonly experienced by breastfeeding mothers. We have previously reported a strong correlation between sore, cracked nipples and S. aureus colonization. A prospective, randomized clinical trial was performed to compare four treatment regimes for S. aureus infected sore nipples. Eighty-four breastfeeding mothers were enrolled in the study. After 5 days to 7 days of treatment, only 8% of mothers showed improvement in the "optimal breastfeeding technique alone" group, 16% improved with topical mupiricin, 29% improved with topical fusidic acid, yet 79% improved with oral antibiotics (p < .0001). Optimal breastfeeding techniques and topical antibiotics ointment failed to heal most infected, sore, cracked nipples. Mastitis developed in 12% to 35% of mothers not treated with systemic antibiotics compared to 5% of mothers treated with systemic antibiotics (p < .005). In conclusion, S. aureus infected sore, cracked nipples should be diagnosed as a potentially widespread impetigo vulgaris and treated aggressively with systemic antibiotics in order to improve healing and decrease the risk of developing mastitis due to an ascending lactiferous duct bacterial infection.

Administration, Cutaneous↗

Successful decolonization of methicillin-resistant Staphylococcus aureus in paediatric patients with cystic fibrosis (CF) using a three-step protocol.

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a bacterial pathogen in patients with cystic fibrosis (CF) although its clinical effects can be variable. The aim of this study was to evaluate the efficacy of a three-step decolonization protocol for MRSA (Belfast CF MRSA decolonization protocol). Of the 17 paediatric patients treated during the five years of the study, eight (47%) were successfully decolonized following one five-day course of oral rifampicin and fusidic acid. The success rate increased to 12 (71%) patients after a second five-day oral treatment course in the 11 patients who remained culture positive at the end of the first treatment cycle. In a further four patients, clearance was achieved with a course of intravenous teicoplanin, increasing the decolonization rate to 16 of 17 patients (94%). These results compare favourably with other published studies and show that MRSA decolonization can be successful in a high proportion of paediatric CF patients.

Adolescent↗

Inactivation of penicillin by purulent exudates.

Four of 22 specimens of human pus inactivated up to 90% of added penicillin within one hour in vitro. Ampicillin and cephaloridine were also inactivated, but streptomycin and fusidic acid were not. The effect was not related to the protein content of the pus, nor to its pH value. Microbes that may produce beta-lactamase in small quantities were isolated from three of the four specimens, but the enzyme was not detected in the pus by physical methods nor by microbiological inhibition assay. The inactivating effect was shown to be a property of the solid portion of the pus, and was absent from the filtrate. We suggest that the effect may be an intrinsic property of the host, which should be investigated further as it has important implications for clinical practice.

Cephaloridine↗

[Finger tip injuries. A comparative study of silver sulfadiazine and fucidin gauze].

Eighty-eight superficial finger-tip lesions were randomized after thorough cleaning to either silver sulphadiazine treatment of Fucidin fusidic acid gauze. In the silver sulphadiazine group the wounds were covered with a non-sterile PVC gloce and redressed at least every third day; in the other group Fucidin gauze was applied and a tubigauze dressing was left in situ for ten days, after which a new dressing was applied. All patients were treated until healed and followed for at least six months after injury. Patients in the silver sulphadiazine group required shorter time for healing and shorter sick leave. The treatment is recommended because of the easy procedure and the good results.

Adult↗

Polycations as outer membrane-disorganizing agents.

The outer membrane-disorganizing effect of a short (10-min) treatment with polycationic agents was studied with smooth Salmonella typhimurium used as a test organism. The polycationic agents were the protamine salmine, a lysine polymer with 20 lysine residues (lysine20), and the deacylated polymyxin B derivative polymyxin B nonapeptide. Two different types of outer membrane-disorganizing were found. Protamine and lysine20 released 20 to 30% of the lipopolysaccharide from the outer membrane and sensitized the bacteria to the anionic detergent sodium dodecyl sulfate but did not (under these conditions) make the bacteria permeable to the hydrophobic probes fusidic acid and actinomycin D. In contrast, polymyxin B nonapeptide did not release lipopolysaccharide or sensitize the bacteria to sodium dodecyl sulfate but made the outer membrane permeable to the hydrophobic probes. None of the agents was bactericidal under the conditions used or caused any leakage of periplasmic beta-lactamase. Polymyxin B was used as a reference and showed characteristic outer membrane-disorganizing action. In thin-section electron microscopy, polymyxin B nonapeptide caused the appearance of long, narrow, finger-like projections on the outer membrane. Protamine and lysine20 caused a distinctly wrinkled appearance of the outer membrane but no projections.

Bacterial Proteins↗

Evaluation of teicoplanin and vancomycin disk susceptibility tests.

Disk tests with two glycopeptide antibiotics, teicoplanin and vancomycin, were evaluated, and MICs were compared with those of fusidic acid and coumermycin. For tests with 30-micrograms vancomycin disks, we recommend modification of the current zone size standards to less than or equal to 10 mm for resistant and greater than or equal 15 mm for susceptible. For teicoplanin disk tests, 30-micrograms disks are recommended, with zone size interpretive standards of less than or equal to 10 and greater than or equal 14 mm. Since no resistant clinical isolates are available at this time, susceptibility testing of either drug is rarely necessary, and zone size standards are tentative.

Aminocoumarins↗

Treatment of angular cheilitis. The significance of microbial analysis, antimicrobial treatment, and interfering factors.

This prospective study evaluated the significance of microbial analysis and antimicrobial treatment for the cure of angular cheilitis. Furthermore, various etiologic factors were investigated for their relative effect on the healing process. The study included 1) an open trial with 50 patients infected by Candida albicans and/or Staphylococcus aureus, and 2) an intraindividual comparison of eight patients with bilateral lesions infected by Candida albicans as the only detected pathogen. After a base-line examination the patients received ointments containing nystatin and/or fusidic acid, on the basis of the outcome of an initial microbial analysis. The patients were evaluated clinically, photographed, and examined for microorganisms at different time intervals. Ninety-six per cent of the patients who participated in the open trial had no sign of infection after 42 days of treatment. Lesions in the double-blind study, treated with nystatin, were healed after 28 days, whereas lesions that received placebo persisted throughout the treatment period. Increasing age, dry skin, and extended skinfolds at the corner of the mouth were factors closely related to the length of the healing process.

Adult↗

Ciprofloxacin-induced, low-level resistance to structurally unrelated antibiotics in Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus.

The effects of ciprofloxacin on the rates of development of low-level resistance to other antibiotics were determined in vitro. Three methicillin-resistant Staphylococcus aureus and two Pseudomonas aeruginosa clinical strains were grown overnight in Mueller-Hinton broth with or without subinhibitory concentrations (1/2, 1/4, and 1/8 MICs) of ciprofloxacin or an aminoglycoside and then quantitatively plated onto medium containing 4 or 8 times the MICs of various antibiotics. The spontaneous mutational frequencies were determined and compared with those of cells not exposed to ciprofloxacin. Exposure of methicillin-resistant S. aureus strains to ciprofloxacin resulted in a > 100-fold increase in the isolation of variants with decreased susceptibilities to ciprofloxacin, tetracycline, imipenem, fusidic acid, and gentamicin, but not vancomycin. Likewise, a > 100-fold increase in the isolation of variants with decreased susceptibilities to ciprofloxacin and imipenem (35-fold) in P. aeruginosa A21213 was observed, and a > 100-fold increase in the isolation of variants with decreased susceptibilities to ciprofloxacin, amikacin, and cefepime in P. aeruginosa A22379 was observed. On the other hand, exposure of these strains to an aminoglycoside did not influence the development of resistance to nonaminoglycoside drugs. These results indicate that exposure to subinhibitory levels of ciprofloxacin can promote the development of low-level resistance to antibiotics with different modes of action.

Amikacin↗

Regulation of protein A biosynthesis in Staphylococcus aureus by certain antibiotics: its effect on phagocytosis by leukocytes.

Protein A, a component of the outer layer of the cell wall of Staphylococcus aureus impairs opsonization by serum complement and thereby delays phagocytosis by polymorphonuclear leukocytes. Two antibiotics with modes of action on bacterial protein biosynthesis, have been used at sub-growth inhibitory concentrations to regulate the production of protein A. Both clindamycin and fusidic acid (either at 1/2 or 1/4 MIC) reduced the amount of protein A on the cell surface. Such drug-grown cells became more susceptible to phagocytic uptake and killing. Chemiluminescence (CL) of PMN when presented with preopsonized drug-grown staphylococci was potentiated and correlated with the enhanced phagocytosis seen earlier. The level of CL appeared to depend upon the amount of human serum used to opsonize the bacteria. Reduced protein A content on the cell surface probably resulted in the exposure of a greater number of receptor sites for C3b, rendering the bacterium more susceptible to attachment and ingestion by the polymorphonuclear leukocyte.

Anti-Bacterial Agents↗

Isolation of spectinomycin resistance mutations in the 16S rRNA of Salmonella enterica serovar Typhimurium and expression in Escherichia coli and Salmonella.

Two single-base mutations in 16S rRNA conferring high-level resistance to spectinomycin were isolated on a plasmid-borne copy of the rrnD operon from Salmonella enterica serovar Typhimurium. Neither of the mutations (C1066U and C1192U) had appreciable effects on cell growth, but each had differential effects on resistance to spectinomycin and fusidic acid. Both mutations also conferred resistance to spectinomycin in Escherichia coli strains containing deletions of all seven chromosomal rrn operons and expressing plasmid-encoded Salmonella rRNA exclusively. In contrast, when expressed in E. coli strains containing intact chromosomal rrn operons, the strains were sensitive to spectinomycin. However, chromosomal mutations arose that allowed expression of the rRNA-dependent spectinomycin resistance phenotype. It is proposed that in heterogeneous rRNA populations, the native E. coli rRNA out-competes the heterologous Salmonella rRNA for binding to ribosomal proteins, translation factors, or ribosome assembly, thus limiting entry of the antibiotic-resistant 30S subunits into the functioning ribosome pool.

Anti-Bacterial Agents↗

Antimicrobial activity of coumermycin and recommendations for disk diffusion tests with 5- and 15-micrograms disks.

Coumermycin was found to be extremely active against methicillin-susceptible and -resistant Staphylococcus spp. (MIC 90, less than or equal to 0.002 microgram/ml). Vancomycin and coumermycin were equally active against Streptococcus spp. (MIC 90s, 0.5 microgram/ml) and both were superior to fusidic acid (MIC 90, 8.0 micrograms/ml). The enterococci had the highest MICs for all three drugs. Disk diffusion susceptibility tests using either 5 or 15 micrograms coumermycin disks seem reliable. The tentative interpretive breakpoints for testing the Staphylococcus spp. only are: 5 micrograms disk-susceptible greater than or equal to 17 and resistant less than or equal to 13 mm; 15 micrograms disk-susceptible greater than or equal to 20 mm and resistant less than or equal to 16 mm. These zone criteria have approximate coumermycin MIC correlates of less than or equal to 0.12 microgram/ml for susceptible and greater than or equal to 0.5 microgram/ml for resistant.

Aminocoumarins↗

Assessment of the potential for microbial resistance to topical use of multiple antimicrobial agents.

The goal of this study was to reduce the likelihood of the generation and/or persistence of bacterial resistance to some antimicrobial components contained in a topical antimicrobial mixture (neomycin, polymyxin B, mupirocin and ciprofloxacin) for use with cultured skin grafts, by substitution of alternative antimicrobials, specifically fusidic acid for mupirocin and ofloxacin for ciprofloxacin. The alternative agents failed to serve that purpose. However, with the exception of specific genera of bacteria, Proteus sp. and Providencia stuartii, 90% or more of all other bacteria tested were susceptible to the action of one or more of the individual antimicrobial agents contained in the original mixture. This was true when bacteria were highly susceptible to the antimicrobials, generally, or when bacteria resistant to specific antimicrobials such as penicillin-class antibiotics and ciprofloxacin, were tested. These results suggest that the redundancy of antimicrobials contained in this mixture reduces the chance that resistant bacteria generated by the use of this mixture or already present on wounds would persist when the mixture is used clinically.

Administration, Topical↗

Comparative investigation of drug delivery of collagen implants saturated in antibiotic solutions and a sponge containing gentamicin.

Collagen implants of various structures and a gelatine sponge were placed in five different antibiotic solutions until complete saturation occurred. The antibiotics were chosen to represent different drug classes (gentamicin sulphate, cefotaxim, fusidic acid, clindamycin, vancomycin). The collagen implants saturated with antibiotic solution and a lyophilized collagen sponge containing gentamicin sulphate were eluated in 0.066 M phosphate buffer (pH = 7.4) at 37 degrees C. The total eluation period is 7 d with buffer changes every 24 h. The antibiotic delivery by the collagen implants and the lyophilized sponge containing gentamicin sulphate is complete after a maximum of 4 d. If an implant that has a protective effect against wound infections over a period of 24-48 h is required, the materials described here are suitable. However, where treatment in infected areas should ensure antibiotic cover for 5-10 d, neither collagen materials immersed in antibiotic solutions nor collagen sponges containing gentamicin are suitable.

Anti-Bacterial Agents↗

In vitro susceptibility of methicillin-resistant Staphylococcus aureus to imipenem and other antimicrobial agents.

Minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations of imipenem, pefloxacin, BMY 28142, were compared with those of vancomycin and other established antistaphylococcal antimicrobial agents, rifampicin, fusidic acid, clindamycin, tobramycin and amikacin against 50 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Imipenem was more active than the other tested antimicrobial agents except for vancomycin which was the most active. The MIC90 of imipenem was 2 micrograms/ml, while the MBC90 was 4.2 micrograms/ml and in all cases the MBCs were only 2-4 times higher than the MICs. Pefloxacin had significant bacteriostatic and bactericidal effect against the majority of the isolates, with an MIC90 of 12.5 micrograms/ml (range 0.4-25 micrograms/ml) and in most cases the bactericidal concentrations were 2-4 times the MIC, with a few isolates having MBCs 8 or more times the MICs. The results obtained confirm that imipenem has excellent in vitro activity against locally isolated MRSA.

Amikacin↗

Microarray-based characterisation of a Panton-Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus.

Recent years have witnessed the emergence of novel methicillin-resistant Staphylococcus aureus (MRSA) strains that produce the potent toxin Panton-Valentine leukocidin (PVL). PVL-positive strains can cause complicated skin infections or necrotising pneumonia with high mortality, and these strains have the potential for epidemic spread in the community. In 2004-2005, two case clusters and two isolated cases were observed in eastern Saxony and southern Brandenburg. These were the first known infections with PVL-positive community-acquired MRSA (caMRSA) in this part of Germany. The isolates belonged to agr type III, spa type 44 or spa type 131, and showed a SmaI macrorestriction pattern that corresponded to caMRSA of clonal group ST80. The isolates were susceptible to levofloxacin, macrolides, clindamycin, gentamicin and vancomycin. Most isolates showed resistance to tetracycline and fusidic acid because of the presence of the tetK and far1 genes. A novel plasmid (designated pUB102) harbouring far1, tetK and blaZ was characterised and partially sequenced. Microarray analysis revealed that the caMRSA isolates harboured genes encoding several bi-component toxins (lukF/S-PVL, lukD/E, lukS/F plus hlgA, and another putative leukocidin homologue). Neither tst1 nor genes for enterotoxins A-Y were detected, but the isolates harboured several staphylococcal enterotoxin-like toxin genes (set genes), as well as genes encoding an epidermal cell differentiation inhibitor (edinB) and exfoliative toxin D (etD). Comparative analysis of other isolates from Australia, Germany, Switzerland and the UK showed that these isolates were representative of a widespread clone of caMRSA.

Adult↗

Treatment and prevention of recurrent staphylococcal furunculosis: clinical and bacteriological follow-up.

Various therapeutic and preventive methods were evaluated in 80 patients with recurrent staphylococcal furunculosis. The most appropriate treatment was peroral antibiotics for 10-14 days, mainly flucloxacillin twice daily. Fusidic acid ointment was used for prevention of relapses. Patients and healthy family members who carried the patient strain applied the ointment in nares twice daily every 4th week during 4-15 months. The method had a permanent effect in 80%. Implantation of strain 502 A was less effective when evaluated during a 2-3 yr period. 40-80 patients were checked up to 8 yr after their last furuncle. Three still had furuncles, in 2 of these cases the original strain was found in nares. 37 patients, now healthy after a mean observation time of 4.5 yr, showed either new nasal strains or negative cultures. A significantly lower frequency of phage group II strains in nares was noted in comparison to the previous findings during active furunculosis.

Adolescent↗