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Biomedical subjects

R Sutherland

Publications and source records attributed to R Sutherland.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1980

The predictive value of myocardial radioisotope scanning in animals treated with doxorubicin.

Thirty-four New Zealand white rabbits were treated with doxorubicin and imaged weekly with Tc-99m pyrophosphate to define the value of abnormal myocardial images in predicting doxorubicin-induced cardiac toxicity. Increased myocardial uptake was detected in most animals on sustained treatment with doxorubicin. A greater proportion of the heart was involved with doxorubicin-related histologic changes in animals with strongly positive myocardial images than in treated animals with moderately positive or normal scans. The myocardial images returned to normal levels 2--6 wk after doxorubicin was discontinued. Five of seven rabbits that received doxorubicin after they had three moderately positive myocardial scans, died from congestive heart failure. Three rabbits whose doxorubicin was discontinued because of scan findings, survived for 6 wk or more before dying from renal failure. The three rabbits who received the highest total dose of doxorubicin died of renal failure without developing abnormal myocardial scans.

Animals↗
PubMed1979

Comparative antibacterial activity of azlocillin, mezlocillin, carbenicillin and ticarcillin and relative stability to beta-lactamases of pseudomonas aeruginosa and klebsiella aerogenes.

The antibacterial activities of two ureidopenicillins, azlocillin and mezlocillin, were compared with those of the alpha-carboxypenicillins, carbenicillin and ticarcillin, against a large number of gram-positive and gram-negative bacteria. All four penicillins were active against a wide range of bacteria including Pseudomonas aeruginosa, but there were differences in the antibacterial spectra and in the antibacterial effects demonstrated by the two classes of penicillins. In particular, the minimum inhibitory concentrations of azlocillin and mezlocillin against Klebsiella aerogenes and against P. aeruginosa were greatly influenced by the size of bacterial inoculum tested whereas there was no significant inoculum effect with carbenicillin and ticarcillin. In stability tests, the ureidopenicillins were inactivated rapidly by the beta-lactamases of K. aerogenes and P. aeruginosa whereas the alpha-carboxypenicillins were stable. It seems probable that the inoculum effect seen with azlocillin and mezlocillin in antibacterial tests with K. aerogenes and P. aeruginosa is associated with the instability of the compounds to the beta-lactamases of these bacteria.

Carbenicillin↗
PubMed1979

Antibacterial activity and synergy, in vitro and in vivo, of a combination of amoxycillin and flucloxacillin.

The antibacterial activity of a combination of equal parts of amoxycillin and flucloxacillin was compared in vitro and in vivo with that of amoxycillin and flucloxacillin against a range of gram-positive and gram-negative bacteria. The combination generally showed additive effects against bacteria sensitive to the individual penicillins and there was no evidence of antagonism, but synergistic effects were observed between amoxycillin and flucloxacillin against certain amoxycillin-resistant gram-negative bacilli. The extent of synergism varied according to the particular bacterial species under test and synergy was observed only against bacteria with chromosomally-mediated beta-lactamases and not against bacteria with R-factor-mediated beta-lactamases. In general, amoxycillin + flucloxacillin demonstrated activity against experimental mouse infections in good agreement with demonstrated activity against experimental mouse infections in good agreement with its in vitro activity, and synergy was produced against a range of gram-negative bacilli in vivo. The data suggest that clinical trial with amoxycillin + flucloxacillin in the treatment of selected infections including those due to some amoxycillin-resistant bacteria may well be justified.

Amoxicillin↗
PubMed1978

Inhibitor of in-vitro granulopoiesis in plasma of patients with renal failure.

Plasmas from 31 patients with moderately severe to severe renal failure inhibited granulopoietic colony formation in human marrow in vitro. The inhibitory activity could not be removed by in-vitro dialysis but was present in an ultrafiltered fraction of molecular weight less than 25 000 daltons. It inhibited the production of colony-stimulating activity (C.S.A.) by leucocytes in the culture system but had little or no effect on preformed C.S.A. or on the granulopoietic colony-forming cell itself. The level of plasma inhibitory activity correlated with the degree of azotaemia but not with the neutrophil or monocyte counts. Despite the potency with which granulopoiesis was inhibited in vitro, none of the patients was severely neutropenic, and only 4 had mild neutropenia (neutrophil count 1.5--2.1 x 10(9)/1).

Bone Marrow↗
PubMed1977

Quinine-induced agranulocytosis: toxic effect of quinine bisulphate on bone marrow cultures in vitro.

In a case of quinine-induced agranulocytosis marrow culture studies confirmed the inhibitory effect on the patient's cells of equivalent therapeutic plasma concentrations of quinine. Similar concentrations had no effect on normal marrow cells. Quinidine, the stereoisomer of quinine, had no effect on either cells from the patient or normal cells. The results encourage the use of in-vitro bone marrow cultures for identifying drugs responsible for agranulocytosis.

Agranulocytosis↗
PubMed1977

Structure--activity relationships in cephalosporins prepared from penicillins. 1. 7beta-Acylamino derivatives of 3-benzyl- and 3-(3-pyridylmethyl)ceph-3-em-4-carboxylic acids.

tert-Butyl 7beta-aminoceph-3-em-4-carboxylates carrying either benzyl or 3-pyridylmethyl substituents at position 3 have been prepared by a multistep modification of the penicillin nucleus. Acylation of either amine, followed by deprotection, gave a range of new cephalosporins. The relationship between structure and antibacterial activity is discussed. D-Phenylglycine proved to be a preferred side chain in both series.

Benzyl Compounds↗
PubMed1977

Structure--activity relationships in cephalosporins prepared from penicillins. 2. Analogues of cephalexin substituted in the 3-methyl group.

A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum antibacterial activity were 3-pyridylmethyl and m- or p-carboxybenzyl. The compounds were only poorly absorbed by the oral route in mice, but the 3-(carboxybenzyl) compounds gave more prolonged useful serum levels than the usual cephalosporins.

Animals↗
PubMed1977

Synergy between ticarcillin and tobramycin against Pseudomonas aeruginosa and Enterobacteriaceae in vitro and in vivo.

The antibacterial activities of ticarcillin, carbenicillin, tobramycin, and gentamicin and of combinations of these antibiotics were measured against Pseudomonas aeruginosa and other gram-negative bacilli in vitro and in experimental mouse infections. Synergistic effects were produced by the penicillin/aminoglycoside combinations in growth inhibition tests and in bactericidal tests against many of the bacteria tested. Combinations of ticarcillin + tobramycin were more active in vitro than carbenicillin + gentamicin against P. aeruginosa but were no more active than the latter against other gram-negative bacilli. Ticarcillin + tobramycin and carbenicillin + gentamicin also demonstrated synergistic activities against P. aeruginosa, Escherichia coli, and Enterobacter cloacae in experimental mouse infection models. Thus, the penicillin/aminoglycoside combinations produced greater protective effects than the individual antibiotics against lethal intraperitoneal infections and also were more effective in reducing kidney counts of viable bacteria and kidney abscess formation in experimental pyelonephritis infections. As was the case in vitro, ticarcillin + tobramycin was more effective than carbenicillin + gentamicin against the experimental P. aeruginosa infections. The results of these in vitro and in vivo studies suggest that combined therapy with ticarcillin and tobramycin may be warranted in the treatment of serious infections due to P. aeruginosa and Enterobacteriaceae.

Animals↗
PubMed1977

Comparative effects of amoxycillin and ampicillin on the morphology of Escherichia coli in vivo and correlation with activity.

An experimental mouse intraperitoneal infection due to Escherichia coli was treated with subcutaneous amoxycillin or ampicillin. Specimens of blood and peritoneal washings from the infected animals were assayed for antibiotic concentrations and examined microscopically for observation of the effects produced by the two penicillins on the morphology of bacteria growing in vivo. Amoxycillin was significantly more effective than ampicillin in protecting the animals from the lethal effects of the infection, although the antibiotic concentrations in the body fluids were very similar for both compounds. However, microscopic examination showed marked differences in the morphological effects produced at equivalent dose levels by the two compounds against the bacteria present in blood and peritoneal fluid. Treatment with amoxycillin at dose levels that produced peak antibiotic concentrations in the body fluids ranging from one-quarter to three times the minimum inhibitory concentration resulted in the formation of spheroplast forms, which lysed rapidly. In contrast, at the same concentrations, ampicillin produced relatively stable filaments or long cell forms, which lysed much more slowly, although at higher dose levels the effects produced were generally similar to those seen with amoxycillin. It is concluded that the superior therapeutic activity of amoxycillin compared with ampicillin is due to its greater bacteriolytic activity in vivo.

Amoxicillin↗
PubMed1977

Aminoglycoside-resistant enterococci.

Thirty-four recent clinical isolates of Streptococcus faecalis were tested for sensitivity to amoxycillin, benzylpenicillin, streptomycin, kanamycin, gentamicin, tobramycin, and amikacin. Amoxycillin was two- to four-fold more active than benzylpenicillin and all strains were inhibited by low concentrations of the penicillins. The aminoglycosides were less active against the enterococci than were the penicillins and a significant number of strains were insensitive or relatively insensitive to one or more of the aminoglycosides. Thus, eight (23%) strains showed a high level of resistance to streptomycin and kanamycin (MIC greater 5000 microng/ml) but were sensitive to gentamicin, tobramycin, and amikacin. In addition, two strains of Strep. faecalis, isolated at different hospitals from patients who had received topical gentamicin therapy, were relatively resistant to gentamicin (MIC250 to 500 microng/ml) and were less sensitive also to the other aminoglycosides. Bactericidal synergy was demonstrated by amoxycillin/aminoglycoside combinations against the enterococci, provided that the test strain of Strep. faecalis was sensitive to the aminoglycoside in the combination. An exception to this was the combination of amoxycillin plus amikacin which was not synergistic against kanamycin-resistant strains of Strep. faecalis although these organisms were sensitive to amikacin in the growth inhibition tests. The gentamicin-resistant strains showed variable responses to amoxycillin/aminoglycoside combinations in tests for bactericidal synergy and were generally less sensitive than typical strains of Strep. faecalis.

Aminoglycosides↗
PubMed1977

Carfecillin: antibacterial activity in vitro and in vivo.

Carfecillin, the alpha-phenyl ester of carbenicillin, hydrolyses rapidly in the presence of serum or body tissues to liberate carbenicillin but hydrolysis is less rapid in aqueous solution. The activity of carfecillin in antibacterial tests in vitro depends upon the extent of hydrolysis to carbenicillin, and in conventional serial dilution tests carfecillin shows an antibacterial spectrum generally similar to that of carbenicillin due to extensive hydrolysis. However, in tests in which the extent of hydrolysis is reduced, carfecillin displays lesser activity than carbenicillin against gram-negative bacilli and greater activity against gram-positive cocci. In the presence of serum carfecillin is hydrolysed rapidly to carbenicillin and the activity shown is solely that of carbenicillin. Unlike carbenicillin, carfecillin is well absorbed in mice after oral administration, producing significant carbenicillin blood concentrations and the compound is as effective by the oral route in the treatment of various experimental mouse infections as is parenteral carbenicillin.

Administration, Oral↗
PubMed1977

Antibacterial activity of antibiotics in acrylic bone cement.

The release of various penicillins and other antibiotics from two brands of polymerised bone cement has been studied in vitro and in vivo in mice. Bone cement plugs containing antibiotics demonstrated antibacterial activity as a result of diffusion of antibiotic from the plugs into the surrounding medium. With all antibiotics tested, from 2-5 to 10 per cent of the antibiotic in the cement was released in vitro in active form within twenty-four hours. Most of the activity appeared within three hours of the start of the test, but in some cases low levels of activity were detected after four days. Antibiotic cement plugs implanted in mice and rats produced low concentrations of antibiotic in the blood up to two hours after implantation, but activity was seldom detected subsequently. In general, penicillins and non-penicillin antibiotics showed similar diffusion characteristics, and the pattern of release in vitro and in vivo was consistent with the leaching of antibiotic from, or near, the surface of the bone cement.

Acrylic Resins↗
PubMed1977

Marrow culture studies in adult acute leukemia at presentation and during remission.

Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100-1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.

Adolescent↗