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Efficacy of antibiotic-coated catheters in preventing subcutaneous Staphylococcus aureus infection in rabbits.

Vascular catheters coated with antiinfective compounds were evaluated as to their ability to prevent Staphylococcus aureus catheter infection in a rabbit model. Zones of inhibition of agar surface-plated S. aureus demonstrated the following hierarchy: dicloxacillin and clindamycin were each better than fusidic acid or chlorhexidine, which were better than ciprofloxacin, cefotaxime, or cefuroxime. In vivo half-lives of inhibitory activity for clindamycin and dicloxacillin were 5.6 and 17.7 h, respectively, with apparent first-order kinetics. Chlorhexidine disappeared in vivo with apparent two-compartment kinetics: first-compartment t1/2, 16.8 h; second-compartment t1/2, 115.6 h. In a rabbit model, dicloxacillin, clindamycin, fusidic acid, and chlorhexidine decreased the risk of infection compared with uncoated control catheters (P < .05). For dicloxacillin, clindamycin, and chlorhexidine, this was true even if the S. aureus inoculation was delayed 48 or 96 h after catheter implantation. These data suggest that vascular catheters with antiinfective coatings should be investigated further in hospitalized patients.

Animals↗

Nasal carriage and antibiotic susceptibility of Staphylococcus aureus in general practice.

The incidence of nasal carriage of Staphylococcus aureus and the in vitro susceptibility of isolates to fusidic acid, penicillin, erythromycin, methicillin and tetracycline was determined in 204 patients who had been treated previously with a short course of a topical preparation of Fucidin for acute skin sepsis, and in an equal number of control subjects. Staphylococcus aureus was isolated from 36 per cent and 34 per cent of patients in the Fucidin and control groups respectively. Only one of the 144 isolates was resistant to fusidic acid. Short, single courses of topical therapy in general practice are unlikely to be epidemiologically hazardous in the long term. Evidence of possible cross-infection in general practice was obtained.

Administration, Topical↗

Antibiotic resistance and enhanced insecticide catabolism as consequences of steroid induction in the gram-negative bacterium Comamonas testosteroni.

The effects of steroid induction on antibiotic resistance against the fungal steroid fusidic acid (ramycin; 16-(acetyloxy)-3 alpha,11 alpha-dihydroxy-29-dammara-17(20), 24-dien-21-oic-acid) as well as on carbonyl reduction and degradation of the novel anti-insect agent NKI 42255 (2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone) were studied in the Gram-negative soil bacterium Comamonas testosteroni strain ATCC 11996. Cells grown with testosterone as inducing agent showed a 5-6-fold elevation of antibiotic resistance against the fungal steroid fusidic acid. Furthermore, testosterone induction caused a faster uptake and different metabolism of the anti-insect agent NKI 42255 compared to control cultures, revealing carbonyl reduction of the substrate keto group as an initial degradation step in induced cells. It is concluded that the formerly described steroid inducible hydroxysteroid dehydrogenases/carbonyl reductases present in Comamonas testosteroni contribute to these altered phenotypes, thus establishing steroid-inducible catabolic pathways as important defense processes against natural and synthetic toxicants in certain bacteria, which are present in the intestinal microflora of mammalian species as well as in soil samples.

Anti-Bacterial Agents↗

Study of developed resistance due to antibiotic treatment of coagulase-negative Staphylococci.

Coagulase-negative Staphylococci (CoNS) are a major cause of postoperative infections. These infections are often associated with foreign material implants and/or a compromised immune system in the patient. Multiresistant strains are increasingly common in the hospital environment and there is concern that the infections will become difficult or impossible to treat. This report is based on a study of 75 patients, with postoperative infections caused by CoNS after thoracic surgery. All patients were treated with surgical revision and antibiotic therapy. One or more bacterial cultures were made in each case, and the resistance pattern of the CoNS found was determined. The goal of the study was to evaluate possible relationships between antibiotic therapy and the appearance of resistance to antibiotics in CoNS found. To describe this relationship, three models were constructed and analyzed by multiple logistic regression. The results indicate an increased resistance to beta-lactam antibiotics and clindamycin after the use of cephalosporins. Also, the use of vancomycin or vancomycin in combination with rifampicin or fusidic acid increases the risk for development of resistance to beta-lactam antibiotics, ciprofloxacin, fusidic acid, clindamycin, netilmycin, and rifampicin. The hypothesis that a combination of antibiotics will curtail the development of resistance was not supported in this study.

Anti-Bacterial Agents↗

GTP degradation to guanine catalyzed by ribosomal subunits and microsomal-wash factors.

Ribosomes from stringent strains of bacteria generate (p)ppGpp if incubated with uncharged tRNA, a ribosomal wash fraction, GTP and ATP. By contrast, an analogous system from rat liver does not transform GTP to (p)ppGpp but degrades it to guanine. The reaction requires the ribosomal subunits, a 40 000-Mr and a 60 000-Mr microsomal wash protein factor and is inhibited if the ribosomal A-site is charged with aminoacyl tRNA. The degradation of GTP to guanine occurs in the following four distinct reaction steps: (a) hydrolysis of GTP to GDP plus Pi, (b) hydrolysis of GDP to GMP plus Pi, (c) hydrolysis of GMP to guanosine plus Pi, (d) hydrolysis of guanosine to guanine plus ribose. The reaction step (a) is inhibited by fusidic acid, cycloheximide, emetine, tetracycline and puromycin. The hydrolysis of GDP is inhibited strongly by fusidic acid, emetine and tetracycline. A putative physiological significance of this ribosome-dependent pathway in the processes of growth control of animal cells under conditions of amino acid deprivation is discussed.

Animals↗

Amplification of chloramphenicol resistance transposons carried by phage P1Cm in Escherichia coli.

We have characterized a number of P1Cm phages which contain the resistance genes to chloramphenicol and fusidic acid as IS1-flanked Cm transposons. Restriction cleavage and electron microscopic analysis showed that these Cm transposons were carried as monomers (M) or tandem dimers (D). Lysogens of P1Cm (D) are more resistant to chloramphenicol than those of its P1Cm (M) presumably as a result of an increased gene dosage. Amplification of the Cm transposons to tandem multimers was frequently observed in P1Cm (D) lysogens grown in the presence of high concentrations of chloramphenicol or fusidic acid and was also detected in P1Cm (M) lysogens. The degree of amplification varied in different clones which suggests that cells containing spontaneously amplified Cm transposons were selected by high doses of the antibiotics. The dimeric as well as the amplified Cm transposons carried in P1Cm lysogens grown in the absence of chloramphenicol displayed considerable stability. Mechanisms for the amplification of the IS1-flanked transposons are discussed.

Chloramphenicol↗

Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections.

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.

Administration, Oral↗

Systemic or local treatment of erythrasma? A comparison between erythromycin tablets and Fucidin cream in general practice.

In a Danish multi-practice study the efficacy of erythromycin tablets (Abboticin 500 mg tablets), fusidic acid cream (Fucidin cream), and placebo was compared in 86 patients (71 men and 15 women) with erythrasma. The patients were treated 'double-blind' for 14 days with either active tablets + placebo cream, placebo tablets + active cream, or placebo tablets + placebo cream. The signs of erythrasma, i.e. colour intensity, demarcation, and scaling of the affected area, as well as degree of fluorescence under Wood's light, were recorded before treatment, after one and two weeks, and at follow-up four weeks later. Cure/improvement was obtained in 77% of the cases in the erythromycin group, 87% in the fusidic acid group, and 42% in the placebo group. There was no difference between the active preparations, whereas both were significantly better than placebo, P = 0.01.

Adolescent↗

Topical fusidic acid/betamethasone-containing gel compared to systemic therapy in the treatment of canine acute moist dermatitis.

The efficacy of a topical preparation containing 0.5% fusidic acid and 0.1% betamethasone-17-valerate was compared to a systemic therapy (comprising a combination of parenteral dexamethasone and oral clavulanate-potentiated amoxycillin) in the treatment of 104 dogs with acute moist dermatitis. Significant improvement was evident after seven days in both treatment groups in all clinical parameters assessed and there was no significant difference in the overall response between the two treatment groups. Staphylococcus intermedius was the most frequently isolated organism from swabs at the first visit (Day 0). No resistance to fusidic acid or clavulanate-potentiated amoxycillin was encountered. The study demonstrates no difference in the clinical improvement achieved in canine acute moist dermatitis following topical or systemic therapy and that both treatment regimes represent effective treatment options for the condition.

Administration, Cutaneous↗

Anti-tumor necrosis factor properties of non-peptide drugs in acute-phase responses.

Dexamethasone (sodium phosphate), pentoxifylline, fusidic acid (sodium salt), pentamidine (isethionate) and R-phenylisopropyladenosine (R-PIA) were tested for their anti-tumor necrosis factor (TNF) activities in an endotoxin-induced shock rat model. All the drugs reduced serum TNF concentrations in a dose-dependent manner, whereas their effects on serum interleukin-6 levels differed. Doses that reduced TNF levels by 50% were 0.012 mg/kg for dexamethasone, 0.06 mg/kg for R-PIA, 0.24 mg/kg for pentamidine, 6.5 mg/kg for fusidic acid and 15 mg/kg for pentoxifylline. Administration of the drugs to rats before intraplantar injection of carrageenan reduced paw edema by 50-70%. Injection of a monoclonal anti-TNF antibody reproduced the inhibitory effect. Moreover, the time course of tissue-associated TNF following carrageenan injection was compatible with mediation of edema by TNF. Results obtained for this acute, non-immunological inflammatory reaction strongly suggest that the model is TNF-dependent. Our results reinforce the idea that TNF is a crucial target in the therapeutics of inflammatory reactions. These drugs, which are able to cross cell barriers, might have clinical applications in localized and/or chronic diseases in which TNF is involved.

Acute-Phase Reaction↗

[Fatty acid composition of Fusidium coccineum lipids].

The fatty acid composition of the lipids synthesized de novo or during growth of the organism producing fusidic acid, Fusidium coccineum on complex media was studied. The content of the total extractable lipids in the mycelium did not exceed 10-11 per cent ty the biomass dry weight. Unsaturated fatty acids with 18 carbon atoms in the chain, mainly oleinic and linoleic acids and saturated fatty acids such as palmitic and stearic acids predominated. The ratio of the main fatty acids and the content of the minor acids were subject to strains and conditions of their cultivation. However, linoleic and oleinic acids predominated in all the lipids except the lipids from submerged cultures growing in the form of unusually large clots. Such lipids contained up to 60 per cent of palmitic acid.

Chromatography, Gas↗

[Morphofunctional characteristics of the development of strains of Fusidium coccineum differing in antibiotic activity in stab cultivation].

The object of the work was to study the morphological and functional characteristics of Fusidium coccineum strains producing fusidic acid and differing in the antibiotic activity. The high metabolic activity of the culture is accompanied by the following morphological characteristics: the cells are rich in ribosomes and mitochondria, they have early vacuolisation, are filled with lipid granules, and then the mycelium undergoes autolysis. As strains with a high activity grow, the structure of the cells changes, the number of ribosomes and mitochondria falls down, and the latter are destroyed. For a long time, the cells contain electron-dense granular structures limited with the membrane and capable of transformation into lipid granules and membranous structures. As was shown by cytochemical studies, the structures have not merely proteins and lipids, but also phosphorus compounds. Their functional role in the fungal metabolism is discussed. As soon as super-synthesis of fusidic acid commences, the cells of the highly active strains are filled with lipid granules associated possibly with the steroid antibiotic. These formations are released from the cell during local lysis of the cell wall and the cytoplasmic membrane.

Bacillus subtilis↗

Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa.

In total, 256 patients with bacteriologically verified impetigo contagiosa were included in three double-blind, parallel group, randomized, multi-centre trials, where the efficacy of hydrogen peroxide cream (Microcid) was compared with that of fusidic acid cream/gel (Fucidin). The trials were performed at 47 centres in three countries, Sweden, Germany and UK, and the results are compiled in the present report. During the course of the 3-week treatment period, 92 patients out of 128 (72%) in the Microcid group were classified as healed, compared to 105 patients out of 128 (82%) in the Fucidin group. This difference was not statistically significant. The reduction in composite sign severity score (the sum of the score for erythema, vesiculation/bullae, weeping and crusting divided by four) in each separate study was 73%, 78% and 84% in the Microcid group and 85%, 85% and 84% in the Fucidin group. No statistically significant differences were found in the separate studies or when compiling the studies in a meta-analysis. When the patients had been classified as healed, beta-haemolytic streptococci were eliminated in all patients treated with Microcid cream. Since treatment started before the result of the bacteriology was known, another 135 patients with negative skin culture were enrolled in the trials, i.e. 391 patients were included in the safety analysis. Out of these, 23 patients reported the occurrence of adverse events, mainly classified as mild. In conclusion, Microcid cream has been documented as a topical alternative to fusidic acid in the treatment of impetigo.

Administration, Cutaneous↗

Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization.

BACKGROUND: Eradication strategies for methicillin-resistant Staphylococcus aureus (MRSA) are variable. We sought to summarize the evidence for use of antimicrobial agents to eradicate MRSA. OBJECTIVES: To describe the effects of topical and systemic antimicrobial agents on nasal and extra-nasal MRSA carriage, adverse events, and incidence of subsequent MRSA infections. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (August 2003), the Cochrane Central Register of Controlled Trials (Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1988 to 2003), handsearched relevant literature, and contacted MRSA experts and the manufacturer of mupirocin. SELECTION CRITERIA: Randomized controlled trials of patients colonized with MRSA comparing topical or systemic antimicrobials to placebo or no treatment, and trials comparing various combinations of topical or systemic agents to no treatment, placebo, or to topical or systemic agents. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial methodological quality, and extracted data. Primary outcomes included eradication of MRSA, infection due to MRSA, and adverse events. MAIN RESULTS: Six trials (384 participants) met the inclusion criteria. No difference in MRSA eradication was detected in four studies: one that compared mupirocin to placebo, two that compared one systemic agent to no treatment (fusidic acid in one and rifampin or minocycline in the other) and one that compared mupirocin to topical fusidic acid and oral trimethoprim-sulfamethoxazole, examining nasal MRSA eradication as an outcome. One study compared minocycline to rifampin, with rifampicin being more effective in relation to eradication of MRSA from all sites at day 30 (relative risk 0.16; 95% confidence intervals 0.02 to 1.00), but the difference at 90 days was not statistically significant (n = 18). Two studies (one testing novobiocin and rifampin, the other ciprofloxacin and rifampin, versus trimethoprim-sulfamethoxazole and rifampin) did not demonstrate a difference in eradication of MRSA at all sites (n = 94). Adverse events with systemic agents occurred in up to 20% of participants, however reporting was sporadic and denominators small. All trials reported development of resistance to antimicrobial agents used. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support use of topical or systemic antimicrobial therapy for eradicating nasal or extra-nasal MRSA. There is no demonstrated superiority of either topical or systemic therapy, or of combinations of these agents. Potentially serious adverse events and development of antimicrobial resistance can result from therapy.

Anti-Bacterial Agents↗

Mechanism of ribosomal translocation. Translocation limits the rate of Escherichia coli elongation factor G-promoted GTP hydrolysis.

The pre-steady-state kinetics of GTP hydrolysis catalysed by elongation factor G and ribosomes from Escherichia coli has been investigated by the method of quenched-flow. The GTPase activities either uncoupled from or coupled to the ribosomal translocation process were characterized under various experimental conditions. A burst of GTP hydrolysis, with a kapp value greater than 30 s-1 (20 degrees C) was observed with poly(U)-programmed vacant ribosomes, either in the presence or absence of fusidic acid. The burst was followed by a slow GTP turnover reaction, which disappears in the presence of fusidic acid. E. coli tRNAPhe, but not N-acetylphenylalanyl-tRNAPhe (N-AcPhe-tRNAPhe), stimulates the GTPase when bound in the P site. If the A site of poly(U)-programmed ribosomes, carrying tRNAPhe in the P site, is occupied by N-AcPhe-tRNAPhe, the burst of Pi discharge is replaced by a slow GTP hydrolysis. Since, under these conditions, N-AcPhe-tRNAPhe is translocated from the A to the P site, this GTP hydrolysis very probably represents a GTPase coupled to the translocation reaction.

Escherichia coli↗

Antibiotic resistance of coagulase-negative staphylococci isolated from artisanal Naples-type salami.

In the present paper 42 isolates from Italian salami were specified as Staphylococcus xylosus (30), Staph. capitis (1), Staph. saprophyticus (1), Staph. hominis (1), Staph. simulans (1), Staph. cohnii (1) and as Staph. spp. (7). These strains were coagulase-negative and were examined for resistance/sensitivity against 25 antibiotics including beta-lactams (7), macrolides (3), amynoglicosides (5), glycopeptides, lincosamides (4) and novobiocin, fusidic acid, chloramphenicol, rifampicin, tetracycline, minocycline. More than 64% of the strains were resistant to lincomycin, penicillin G, amoxicillin, fusidic acid and novobiocin. All the strains were multiresistant and displayed at least three resistances. Over 75% had a multiple antibiotic resistance (MAR) index between 0.2 and 0.5.

Animals↗

Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility.

Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

Acetamides↗

Antibiotic accumulation in human polymorphonuclear leucocytes and lymphocytes.

Human polymorphonuclear leucocytes and lymphocytes were incubated with 10 different radiolabelled antibiotics (10 micrograms/ml) for 2 hours. The ratio of cellular concentration to extracellular concentration of the drugs was determined after centrifugation. For beta-lactam antibiotics and gentamicin the ratios were less than 1.0. The ratios for doxycycline, erythromycin, fusidic acid and rifampicin were 13, 4.3, 7-10 and 2.5 respectively indicating a cellular accumulation of these drugs. Erythromycin, fusidic acid and rifampicin were rapidly released from the cells in antibiotic free medium, while doxycycline was partly irreversibly bound.

Anti-Bacterial Agents↗