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Biomedical subjects

J M Hamilton-Miller

Publications and source records attributed to J M Hamilton-Miller.

At least 271 records · Page 15Linked to original sources
PubMed1974

Cefoxitin and cephalothin: antimicrobial activity, human pharmacokinetics, and toxicology.

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indole-producing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

Adult↗
PubMed1974

Comparative activity of ampicillin and seven cephalosporins against group D streptococci.

Minimum inhibitory concentrations have been determined for ampicillin and seven cephalosporins against 93 strains of group D streptococci isolated recently from clinical material. Ampicillin was much the most active compound (modal MIC = 1.6 mug/ml); cephaloridine, cephacetrile, and cefazolin had a modal MIC of 25 mug/ml, while corresponding figures for cephalothin, cephradine, cephalexin, and cefoxitin were 50, 100, 200, and 800 mug/ml, respectively. Thus, none of the newer cephalosporins is an improvement in respect to activity against enterococci over existing compounds, and ampicillin remains overwhelmingly the beta-lactam antibiotic of choice for the treatment of infections by such organisms. Pharmacokinetic considerations, however, indicate that certain cephalosporins, for instance, cephaloridine, cefazolin, and cephanone, may be worthy of further study in view of possible synergy with aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1973

Cefoxitin, a new semi-synthetic cephamycin: an in-vitro and in-vivo comparison with cephalothin.

The activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indole-producing Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by beta-lactamases produced by Gram-negative organisms. Against Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood levels.Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.

Adolescent↗
PubMed1971

Specificities of haemagglutinating antibodies evoked by members of the cephalosporin C family and benzylpenicillin.

1. Antisera have been produced in rabbits to benzylpenicillin and four members of the cephalosporin C family and to conjugates of these substances with bovine gamma-globulin. 2. Deacetoxycephalosporin C reacted less readily and deacetylcephalosporin C lactone more readily with bovine gamma-globulin than did benzylpenicillin, cephalosporin C or deacetylcephalosporin C. 3. Antisera to free or conjugated benzylpenicillin agglutinated red cells sensitized with a variety of penicillins, but only reacted to a significant extent with cells sensitized with the cephalosporins tested when the latter contained an N-phenylacetyl or chemically related side chain. 4. Antisera to members of the cephalosporin C family agglutinated cells sensitized with these cephalosporins or with penicillin N, but did not react with cephalosporins whose side chains were chemically unrelated to alpha-aminoadipic acid. 5. Members of the cephalosporin C family and products of hydrolysis of cephalosporin C behaved as hapten inhibitors of antisera to cephalosporin C, but 7-aminocephalosporanic acid was relatively ineffective. 6. These findings are discussed in relation to differences in the chemical properties of penicillins and cephalosporins.

Animals↗
PubMed1970

Products of aminolysis and enzymic hydrolysis of the cephalosporins.

1. The reaction of cephalosporins with ammonia, amino acids and other simple amino compounds in weakly alkaline aqueous solutions yields labile compounds with lambda(max.) 230nm. The reaction of deacetyl- and deacetoxy-cephalosporins under similar conditions yields compounds with lambda(max.) 260nm. 2. Hydrolysis with a beta-lactamase results in the formation of compounds with lambda(max.) 230nm from deacetylcephalosporins and cephalosporins, but not from deacetoxycephalosporins. 3. These different compounds decompose to give penaldates and penamaldates derived from the side chain and the carbon atoms of the beta-lactam ring. 4. Derivatives similar to those obtained with simple amino compounds appear to be formed when cephalosporins and their analogues react with lysine polymers. 5. Some of the chemical and physical properties of the various derivatives have been studied and tentative structures for them are proposed. 6. Possible implications of the results in relation to the immunological properties of the cephalosporins are discussed.

Amino Acids↗