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Biomedical subjects

C Reading

Publications and source records attributed to C Reading.

54 records · Page 3Linked to original sources
PubMed1986

Structure-activity relationships amongst beta-lactamase inhibitors.

Using a variety of beta-lactamases including those from Escherichia coli (TEM-1), Enterobacter cloacae P99 and Staphylococcus aureus the inhibition profiles (I50 values) were determined for various groups of compounds including penicillins, penicillanic acid derivatives (sulphone and beta-halo substitutions), olivanic acids and clavulanic acid derivatives including substituted ethers and amines. Some of the latter compounds had higher activity than clavulanic acid with and without preincubation of enzyme with inhibitor but they still had poor activity against the P99 enzyme. Improvements in activity against Class I cephalosporinases were obtained with some derivatives of clavulanic acid but this was usually achieved at the expense of activity against clavulanate susceptible beta-lactamases. The olivanic acids had the highest activity against the widest range of beta-lactamases.

Bacteria↗
PubMed1985

Beta-lactamase stability of temocillin.

The stability of temocillin to 12 different beta-lactamase preparations was studied using high pressure liquid chromatography and was compared with that of aztreonam, cefotetan and cefotaxime. Temocillin was the most stable beta-lactam examined, being as stable as cefotetan to most of the beta-lactamases tested. However, cefotetan was hydrolysed at measurable rates by the beta-lactamase of Enterobacter cloacae P99, in contrast to temocillin which was completely stable to this enzyme. Aztreonam was hydrolysed at a slow rate by many of the preparations, being especially labile to the enzyme from Klebsiella oxytoca K1. Cefotaxime was hydrolysed at varying rates by all the preparations.

Anti-Bacterial Agents↗
PubMed1983

The beta-lactamase stability of amoxycillin with the beta-lactamase inhibitor, clavulanic acid.

The stability of low concentrations of amoxycillin in the presence of clavulanic acid (potassium salt) was determined for a wide range of clinically important beta-lactamases including the staphylococcal and TEM plasmid mediated enzymes. Even with enzyme preparations which completely hydrolysed the amoxycillin within a minute, clavulanic acid provided significant protection. The time course of the protection of amoxycillin reflected the time dependent action of clavulanic acid.

Amoxicillin↗
PubMed1982

beta-Lactamases of Branhamella catarrhalis and their inhibition by clavulanic acid.

Three of four clinical isolates of Branhamella catarrhalis from Belgium produced a beta-lactamase identical to enzymes previously reported to occur in French and British isolates of this organism. One strain, however, produced a new type of beta-lactamase. Both beta-lactamase types were readily inhibited by low concentrations of clavulanic acid.

Aerobiosis↗
PubMed1982

Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography.

Augmentin is a new antibacterial formulation comprised of amoxicillin and the beta-lactamase inhibitor clavulanic acid. In the present paper, the use of high-performance liquid chromatography (HPLC) to provide a rapid assay of the components of Augmentin in body fluids is described. Clavulanic acid was assayed by reacting the sample with imidazole, which readily produces a derivative absorbing at 311 nm. This derivative chromatographs on reverse-phase HPLC columns clear of interfering components in both human serum and urine. Concentrations of clavulanic acid as low as 0.1 microgram/ml were readily detectable in human serum with this procedure. There was no interference from amoxicillin, amoxicillin penicilloic acid, or the acid and alkali degradation products of clavulanic acid when this assay system was used. Amoxicillin in body fluids was assayed directly by HPLC without derivatization. The same chromatographic conditions were employed for the assay of amoxicillin and the clavulanic acid derivative, simplifying the methodology. Amoxicillin, however, was determined of the antibiotic per ml. An alkali blanking procedure for amoxicillin and clavulanic acid is also described which allows the detection of any underlying peaks which may cochromatograph. The use of ultrafiltration to remove protein from serum samples before HPLC was successfully applied to the assay of clavulanic acid and amoxicillin. Ultrafiltration is not an essential procedure for these assays, but it prolongs column life and reduces interference in the amoxicillin assay. Results obtained by HPLC were compared with those obtained by using microbiological assays.

Amoxicillin↗
PubMed1982

The inhibition of bacterial beta-lactamases by some monocyclic beta-lactams.

The inhibition characteristics of 25 monocyclic beta-lactams mainly with an amido function at C3 have been studied against the beta-lactamases produced by 4 bacterial types. Significant levels of inhibition were found for only a few of the compounds tested and primarily against Staphylococcus beta-lactamase. The most active inhibitor tested, 3-p-nitrophenylacetamido-4-phenylazetidin-2-one, was found to require a cis geometry, the trans isomer being almost inactive.

Anti-Bacterial Agents↗
PubMed1981

The inhibition of beta-lactamases from gram-negative bacteria by clavulanic acid.

The beta-lactamase from Klebsiella pneumoniae E70 behaved in a similar fashion to the TEM-2 plasmid mediated enzyme on reaction with clavulanic acid. Both enzymes produced two types of enzyme-clavulanate complex, a transiently stable species (t((1/2))=4min at pH7.3 and 37 degrees C) and irreversibly inhibited enzyme. In the initial rapid reaction (2.5min) the enzymes partitioned between the transient and irreversible complexes in the ratios 3:1 for TEM-2 beta-lactamase and 1:1 for Klebsiella beta-lactamase. Biphasic inactivation was observed for both enzymes and the slower second phase was rate limited by the decay of the transiently stable complex. This decay released free enzyme for further reaction with fresh clavulanic acid, the products again partitioning between transiently stable and irreversibly inhibited enzyme. This cycle continued until all the enzyme had been irreversibly inhibited. A 115 molar excess of inhibitor was required to achieve complete inactivation of TEM-2 beta-lactamase. Hydrolysis of clavulanic acid with product release appeared to occur with the inhibition reaction, which explained this degree of clavulanic acid turnover. The stoichiometry of the interaction with Klebsiella beta-lactamase was not examined. The penicillinase from Proteus mirabilis C889 was rapidly inhibited by low concentrations of clavulanic acid. The major product was a moderately stable complex (t((1/2))=40min at pH7.3 and 37 degrees C); the proportion of the enzyme that was irreversibly inactivated was small. The cephalosporinase from Enterobacter cloacae P99 had low affinity for the inhibitor and only reacted with high concentrations of clavulanic acid (k=4.0m(-1).s(-1)) to produce a relatively stable complex (t((1/2))=180min at pH7.3 and 37 degrees C). No irreversible inactivation of this enzyme was detected. The rates of decay of the clavulanate-enzyme complexes produced in reactions with Proteus and Enterobacter enzymes were markedly increased at acid pH.

Clavulanic Acid↗
PubMed1980

Sensitivity to carbenicillin and ticarcillin, and the beta-lactamases of Pseudomonas aeruginosa in the UK in 1978-79.

A total of 438 strains of Pseudomonas aeruginosa supplied by 10 hospitals in the UK reporting an increase in resistance to carbenicillin was tested for sensitivity to carbenicillin and ticarcillin. It was found that 85% of the strains were inhibited by 125 microgram carbenicillin/ml and 87% by 50 microgram ticarcillin/ml, and that ticarcillin was from two- to four-fold more active than carbenicillin against the majority of these strains. Strains with a high level of resistance to carbenicillin (MIC greater than 1000 microgram/ml) possessed constitutive beta-lactamases, and five different types of enzyme were identified. There was good correlation between minimum inhibitory concentrations and the results of disc sensitivity tests in this study, 82% with the 100 microgram carbenicillin disc and 90( with the 75 microgram ticarcillin disc, but results reported in the hospital laboratory tests with the carbenicillin disc were less satisfactory (64% correlation). From a comparison with data reported in 1967 there does not appear to have been a significant increase in the incidence of carbenicillin-resistant strains of Ps aeruginosa in the UK.

Carbenicillin↗
PubMed1979

The inhibition of staphylococcal beta-lactamase by clavulanic acid.

Clavulanic acid inhibited both the extracellular and cell-extract beta-lactamases of the four Staphylococcus aureus strains tested. The inhibition of S. aureus Russell cell-extract enzyme appeared to be active-site-directed and proceeded in a first-order fashion consistent with the formation of a covalent intermediate. Inhibited enzyme free of excess clavulanic acid was shown to regenerate enzyme activity slowly at pH 7.0, but the rate of reactivation increased at acid pH. When the enzyme was incubated with excess clavulanic acid complete inhibition was rapidly obtained, during further incubation clavulanic acid was shown to disappear slowly and complete loss of clavulanic acid from the reaction mixture coincided with the onset of the return of enzyme activity. A reactive enamine resulting from enzymic hydrolysis of the beta-lactam ring of clavulanic acid has been proposed as a possible intermediate in the inhibitory mechanism.

Anti-Bacterial Agents↗
PubMed1979

Holomycin and an antibiotic (MM 19290) related to tunicamycin, metabolites of Streptomyces clavuligerus.

Streptomyces clavuligerus produces penicillin N, several cephalosporins and the beta-lactamase inhibitor clavulanic acid. The detection, isolation and properties of further metabolites of this culture, MM 21801 and MM 19290, are described. MM 21801 was identified as the antibiotic holomycin. MM 19290 was shown to be related to tunicamycin, an antibiotic complex obtained from cultures of Streptomyces lysosuperificus.

Anti-Bacterial Agents↗
PubMed1977

Clavulanic acid: a beta-lactamase-inhiting beta-lactam from Streptomyces clavuligerus.

A novel beta-lactamase inhibitor has been isolated from Streptomyces clavuligerus ATCC 27064 and given the name clavulanic acid. Conditions for the cultivation of the organism and detection and isolation of clavulanic acid are described. This compound resembles the nucleus of a penicillin but differs in having no acylamino side chain, having oxygen instead of sulfur, and containing a beta-hydroxyethylidine substituent in the oxazolidine ring. Clavulanic acid is a potent inhibitor of many beta-lactamases, including those found in Escherichia coli (plasmid mediated), Klebsiella aerogenes, Proteus mirabilis, and Staphylococcus aureus, the inhibition being of a progressive type. The cephalosporinase type of beta-lactamase found in Pseudomonas aeruginosa and Enterobacter cloacae P99 and the chromosomally mediated beta-lactamase of E. coli are less well inhibited. The minimum inhibitory concentrations of ampicillin and cephaloridine against beta-lactamase-producing, penicillin-resistant strains of S. aureus, K. aerogenes, P. mirabilis, and E. coli have been shown to be considerably reduced by the addition of low concentrations of clavulanic acid.

Amidohydrolases↗
PubMed1976

Biofeedback control of migraine: a pilot study.

A group of six subjects was trained, using biofeedback procedures, in the voluntary regulation of hand temperature as a means of controlling migraine attacks. The training procedure and its relationship to migraine activity is described. Daily records of migraine activity were kept during base-line, training, and follow-up periods. Analysis of this data revealed statistically and clinically significant improvement on several indices of migraine activity. Evidence for a concomitant improvement in the ability of subjects to produce voluntary increases in hand temperature is presented.

Adult↗