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Biomedical subjects

R Sutherland

Publications and source records attributed to R Sutherland.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1976

Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins.

Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins. In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin. The phthalidyl ester of ampicillin [talampicillin (British Pharmacopoeia approved name), BRL 8988] was selected for extended studies. The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself.

Administration, Oral↗
PubMed1975

Smoking and pregnancy.

Smoking is associated with decreased fertility in both males and females, an increased abortion rate, lowered birth weight, an increased still birth rate and probably an increased neonatal death rate. There is also a reduced incidence of maternal hypertension (although the babies are at even greater risk), an increased incidence of ante-partum haemorrhage, impaired brain development and possible teratogenic effects. These effects can be reversed if the mother gives up smoking in pregnancy.

Animals↗
PubMed1975

Preparation, hydrolysis, and oral absorption of alpha-carboxy esters of carbenicillin.

Twelve alpha-carboxy esters of carbenicillin, a parenteral broad spectrum semisynthetic penicillin, were synthesized and examined as potential oral carbenicillin derivatives. The rates at which the esters were hydrolyzed in vitro to carbenicillin by animal and human tissues were compared and the carbenicillin serum levels arising after oral administration of the esters were measured in squirrel monkeys and human volunteer subjects. The alpha-carboxyphenyl ester of carbenicillin [carfecillin (British Pharmacopoeia approved name), BRL 3475] WAS SELECTED FOR FURTHER STUDY AND IS PRESENTLY UNDERGOING CLInical trial.

Absorption↗
PubMed1975

Activity of amoxycillin against enterococci and synergism with aminoglycoside antibiotics.

Amoxycillin was more active in vitro than ampicillin or benzylpenicillin against clinical isolates of enterococci. All 55 strains tested were sensitive to the three penicillins but 15 strains showed a high level of resistance to streptomycin and two of these were also insensitive to kanamycin. All strains were sensitive to gentamicin, which was the most active of the aminoglycoside antibiotics. The penicillins showed pronounced bactericidal activity against the enterococci but failed to sterilise cultures of these organisms. Combinations of penicillins and aminoglycosides invariably produced synergistic bactericidal effects which resulted in sterilisation of cultures of these organisms. Combinations of penicillins and aminoglycosides invariably produced synergistic bactericidal effects which resulted in sterilisation of cultures of enterococci provided that the strain was sensitive to the aminoglycoside moiety of the antibiotic combination. Synergism was not observed with a combination of a penicillin and an aminoglycoside when the enterococcus was resistant to the aminoglycoside. The data reported suggest that amoxycillin may have certain advantages, compared with ampicillin or benzylpenicillin, for the treatment of enterococcal infections.

Amoxicillin↗
PubMed1975

Comparative effects of amoxycillin and ampicillin in the treatment of experimental mouse infections.

Amoxycillin was significantly more active than ampicillin in the treatment of intraperitoneal mouse infections when administered by oral and parenteral routes, although the causal bacteria were equally susceptible in vitro to the two penicillins. Amoxycillin produced higher antibiotic blood concentrations in mice than ampicillin after oral administration, and this was a possible explanation for the superior oral activity of amoxycillin. In contrast, antibiotic blood concentrations were the same for both compounds after subcutaneous injection, but it was demonstrated that amoxycillin was more effective than ampicillin by this route in reducing bacterial counts in the peritoneal cavity and in the blood of mice infected with Escherichia coli. Amoxycillin was also significantly more active than ampicillin in the treatment of infection by intraperitoneal dosing as a result of greater bactericidal activity in infected mice together with the production of higher antibiotic blood levels. The results of these studies on the effects of parental treatment of experimental infections with the two penicillins show that the superior chemotherapeutic activity of amoxycillin was associated with the greater bactericidal activity of amoxycillin in vivo and with differences in the distribution of the two penicillins in the infected animal.

Amoxicillin↗
PubMed1973

Transferable antibiotic resistance in enteropathogenic Escherichia coli between 1948 and 1968.

Enteropathogenic strains of Escherichia coli which had been isolated in the United Kingdom during three periods between 1948 and 1968, namely 1948 to 1951, 1957 to 1960, and 1967 to 1968, were tested for susceptibility to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulphonamides. Antibiotic-resistant strains were tested for their ability to transfer antibiotic resistance to an antibiotic-susceptible strain of E. coli K-12. A relatively high proportion of strains isolated between 1948 and 1951 was resistant to ampicillin, streptomycin, or sulphonamides. None of these strains transferred ampicillin or streptomycin resistance, but sulphonamide resistance was R-factor-mediated in three out of 14 sulphonamide-resistant strains. Resistance to tetracycline and chloramphenicol was rare before 1951 but had become common among enteropathogenic E. coli by 1957. Much of the antibiotic resistance of bacteria isolated between 1957 and 1960 was R-factor-mediated, and transferable resistance was about as prevalent among E. coli isolated between 1957 and 1960 as among strains isolated in 1967 and 1968. Nevertheless, there was no appreciable increase in the overall incidence of antibiotic resistance among these enteropathogenic strains of E. coli between 1957 and 1968, although transferable antibiotic resistance was common during this period. These results do not suggest that the emergence of transferable antibiotic resistance will inevitably lead to the rapid development of antibiotic resistance among this group of bacteria.

Anti-Bacterial Agents↗
PubMed1972

Amoxycillin: a new semi-synthetic penicillin.

Amoxycillin (alpha-amino-p-hydroxybenzylpenicillin) is a new semi-synthetic penicillin with a broad spectrum of antibacterial activity similar to that of ampicillin. Penicillin-sensitive strains of staphylococci, streptococci, and pneumococci were sensitive to concentrations of 0.1 mug or less of amoxycillin/ml. Strains of Haemophilus influenzae were inhibited by a level of 0.5 mug/ml, and most strains of Escherichia coli, Proteus mirabilis, Shigella sonnei, Salmonella species, and Streptococcus faecalis were sensitive to a concentration of 5 mug or less of amoxycillin/ml. Penicillinase-producing strains of Staphylococcus aureus and strains of Pseudomonas aeruginosa, indole-positive Proteus, Klebsiella, and Enterobacter were insensitive to amoxycillin. The new penicillin was bactericidal in activity, as with other penicillins, and its antibacterial activity was not reduced in the presence of serum. After oral administration to volunteer subjects amoxycillin produced serum concentrations twice as high as those obtained with similar doses of ampicillin, and the penicillin was recovered unchanged in high concentrations in the urine. The absorption of amoxycillin was not greatly influenced by food, and administration of probenecid resulted in increased and more prolonged concentrations of amoxycillin in serum.

Administration, Oral↗