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G N Rolinson

Publications and source records attributed to G N Rolinson.

At least 19 recordsLinked to original sources
PubMed1994

A review of the microbiology of amoxycillin/clavulanic acid over the 15 year period 1978-1993.

A review of the published literature over the period 1978-1993 was undertaken to assess any changes in the prevalence of beta-lactamase-producing bacterial pathogens and also any changes in the susceptibility in these pathogens to amoxycillin/clavulanate. The review has involved the examination of over 1500 publications. The review shows that in general there has been an increase in the frequency of beta-lactamase-producing pathogens resistant to ampicillin and amoxycillin but there is no evidence for any significant increase in resistance to amoxycillin/clavulanate over the period of the review.

Amoxicillin↗
PubMed1991

Evolution of beta-lactamase inhibitors.

In most clinical isolates that are resistant to penicillins, cephalosporins and related compounds, the mechanism of resistance is the production of beta-lactamase enzymes. These enzymes hydrolyze the amide bond in the beta-lactam ring of the compound, producing acidic derivatives that have no antibacterial properties. The rationale for beta-lactamase inhibitors is to overcome this resistance. Early study of beta-lactamase inhibition was begun in the 1940s without success. Interest in beta-lactamase inhibition was renewed with the development of the semisynthetic penicillins in the early 1960s, when it was found that certain of these compounds could function as inhibitors. However, none found clinical application. The screening of microorganisms for possible production of naturally occurring beta-lactamase inhibitors resulted in the discovery of the olivanic acids and, later, clavulanic acid. A formulation of clavulanic acid with amoxicillin was introduced in 1981, and a formulation of clavulanic acid with ticarcillin appeared shortly thereafter. More recently, other beta-lactamase inhibitors have been developed, including sulbactam and tazobactam. A formulation of sulbactam with ampicillin has appeared recently. As a result of beta-lactamase inhibition, amoxicillin and clavulanate and ticarcillin and clavulanate are active against a high proportion of amoxicillin resistant and ticarcillin resistant pathogens. These formulations have been shown to be safe and effective in the treatment of many infections that would not be expected to respond to amoxicillin or ticarcillin alone.

Anti-Bacterial Agents↗
PubMed1988

Sensitivity of clinical isolates from German hospitals to amoxicillin/clavulanic acid (Augmentin) compared with other antibiotics.

17,244 pathogens isolated from clinical specimens of 24 hospitals in the Moers area (North-Rhine Westphalia, FRG) were tested in regard to their susceptibility to Augmentin (amoxicillin and clavulanic acid). For this purpose, minimal inhibitory concentrations were determined by use of microbroth dilution technique. 80% of Gram-negative, 98% of Gram-positive and 97% of anaerobic isolates were susceptible to Augmentin (breakpoint 4 mg/l amoxicillin in the presence of 2.5 mg/l clavulanic acid). In a second part of the study the susceptibility to Augmentin of 4.137 Gram-negative and 10.958 Gram-positive pathogens was compared to their sensitivity against benzylpenicillin, flucloxacillin, mezlocillin, erythromycin, clindamycin, fusidic acid, ampicillin, cefaclor and doxycyclin.

Amoxicillin↗
PubMed1988

Evolution of beta-lactamase inhibitors.

Beta-lactamase, the bacterial enzyme that can inactivate penicillins, cephalosporins and related antibiotics, can function outside the cell or in the periplasmic space. This resistance can be transferred between bacteria of the same or different species. Most strains of Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella, Enterobacter, Pseudomonas aeruginosa and Bacteroides species are beta-lactamase producers. Clavulanic acid is a beta-lactamase inhibitor that works by blocking the enzyme center. When it is combined with amoxicillin and ticarcillin, it expands those drugs' spectrum of activity to bacteria that are resistant to the single antibiotics as well as to anaerobic bacteria.

Anti-Bacterial Agents↗
PubMed1984

Tissue penetration of antibiotics.

A novel method of deduction is described for determining the amount of antibiotic present in the tissues at any point in time following intravenous administration of a given dose. Application of this calculation to amoxycillin, carbenicillin, ticarcillin, nafcillin, dicloxacillin and temocillin indicates that the passage of drug from the vascular compartment to the extravascular fluid is rapid. The results obtained with this method of calculation are discussed in relation to the results obtained by conventional pharmacokinetic analysis and by direct assay of tissue fluid samples.

Anti-Bacterial Agents↗
PubMed1984

Factors affecting the apparent regrowth of Pseudomonas aeruginosa following exposure to bactericidal concentrations of carbenicillin.

Factors have been identified which are responsible for the phenomenon already reported in which regrowth of Pseudomonas aeruginosa was found to occur in broth cultures containing bactericidal concentrations of carbenicillin. In cultures incubated under stationary conditions, in a water bath, the factor primarily responsible for this phenomenon of regrowth appears to be the formation of condensate on the inside of the culture vessel. In such condensate, viable cells of P. aeruginosa were found in numbers equal or higher than those in the culture broth. As a result of coalescing, and running down the vessel wall, the condensate provides a continuous reintroduction of bacteria into the culture medium, and, notwithstanding a bactericidal concentration of antibiotic in the medium, this process of continual reinoculation leads to the formation of visible growth and an increase in the viable count in the culture medium after an initial bactericidal effect. In silicone-treated flasks, incubated in a water bath, regrowth did not occur. Under such conditions, condensate again formed, but only as discrete droplets on a non-wetting surface, and in such condensate the bacterial count was found to be low. In flasks incubated in an air incubator, condensate did not form, and under these conditions the phenomenon of regrowth was not observed.

Carbenicillin↗
PubMed1983

Effect of protein binding on antibiotic activity in vivo.

Using a group of penicillins all belonging to the same chemical class, antibacterial activity against Staphylococcus aureus was determined in vitro and also in vivo by use of an intraperitoneal infection in mice. The compounds all showed essentially the same level of activity in vitro but differed markedly in their activity in vivo. This activity in vivo could be correlated directly with the extent of binding in mouse serum.

Animals↗
PubMed1982

The history and background of Augmentin.

Bacterial resistance to the beta-lactam group of antibiotics is frequently due to the production of beta-lactamase which brings about the inactivation of the antibiotic. Clavulanic acid is a naturally occurring inhibitor of beta-lactamase which is capable of rendering penicillin- and cephalosporin-resistant organisms sensitive. The compound is obtained by fermentation from Streptomyces clavuligerus. Clavulanic acid shows some structural similarity to the penicillins and cephalosporins and functions as a progressive inhibitor of a wide range of beta-lactamases including those found in Escherichia coli, Klebsiella aerogenes, Proteus species, Bacteroides fragilis, Haemophilus influenzae, Neisseria gonorrhoeae and Staphylococcus aureus. Clavulanic acid is well absorbed when given by mouth and a formulation with amoxycillin (Augmentin; Beechams) is now available for clinical use.

Amoxicillin↗
PubMed1981

Regrowth of Pseudomonas aeruginosa and other bacteria after the bactericidal action of carbenicillin and other beta-lactam antibiotics.

Exposure of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus to bactericidal concentrations of beta-lactam antibiotics in broth culture resulted in a decrease in viability over the first 6--8 hr, followed by regrowth which was not due to the selection of resistant variants or loss of antibiotic potency. During incubation, bacteria adhered to the surface of the culture vessel and multiplied despite the presence of bactericidal concentrations of antibiotic in the medium. It is concluded that the phenomenon of "regrowth" results from such adhesion and the subsequent dispersal of some of these cells into the culture medium. The significance of these findings is discussed in relation to the treatment of infection, the determination of minimal bactericidal concentrations, and the phenomena of tolerance and persisters.

Carbenicillin↗
PubMed1980

Selection of variants of Pseudomonas aeruginosa resistant of Beta-lactam antibiotics.

In broth cultures of Pseudomonas aeruginosa, containing carbenicillin or azlocillin, regrowth occurred after a period of bactericidal action, to reach visible proportions overnight. Regrowth in the presence of relatively high concentrations of carbenicillin or azlocillin could not be accounted for on the basis of growth of resistant variants nor as a result of drug inactivation. On the other hand, resistant variants could be selected from the regrowth which occurred at concentrations of carbenicillin or azlocillin only slight in excess of the minimum inhibitory concentrations (MIC). Antibiotic resistant variants could also be isolated from individual colonies growing on agar plates containing carbenicillin, ticarcillin, azlocillin or piperaccillin at concentrations above the MIC for the majority of the population. Two types of resistant variant were isolated. The first showed a 2-5 fold increase in resistance to carbenicillin, ticarcillin, azlocillin and piperacillin while Beta-lactamase production in these variants appeared to be unchanged. The second type of resistant variant showed unchanged sensitivity to carbenicillin and ticarcillin, or only a slight increase in resistance, whereas resistance to azlocillin and piperacillin was increased as much as 40-fold or more. These variants showed increased constitutive Beta-lactamase production and may be derepressed mutants of the parent culture. Variants of this type were readily selected by culture in the presence of azlocillin or piperacillin but only infrequently as a result of culture in the presence of carbenicillin or ticarcillin. The existence in cultures of P. aeruginosa of variants showing elevated Beta-lactamase production may account at least in part for the effect of inoculum size on the activity of azlocillin and piperacillin against P. aeruginosa and the marked discrepancy between MIC and minimum bactericidal concentration (MBC) which is characteristic of the ureido penicillins.

Animals↗
PubMed1980

Basis and results of therapy with Beta-lactam antibiotics in experimental infections.

Experimental infections in animals and their chemotherapy are dependent on a variety of experimental conditions and parameters which may be themselves interrelated; the type and number of infecting organisms, the nature of the infection, the antibiotic chosen for therapy and its administration schedule can influence the results of animal studies. One additional factor which applies to dosage of penicillins is the phenomenon of the recovery period, i. e. the period of time which surviving bacteria need to resume growth after removal of the drug. The bactericidal effect probably strongly influences the period of time which is required before the number of viable organisms reach the level present at the time of infection. Thus one can assume that it is the extent of the bactericidal effect which influences the period of time between doses rather than the recovery period. Besides these parameters the physiological state of the infecting organism may also be important. The results of penicillin therapy vary considerably depending on the bacterial growth rate. Differences in the nature of infection in experimental animals and man and the physiology of animals and man do not allow close simulation of clinical infections under experimental conditions. However the factors discussed may provide some guidelines for rational antibiotic treatment in man.

Animals↗