PubMed Health⌕ Search

Biomedical subjects

J A Weisbach

Publications and source records attributed to J A Weisbach.

At least 37 records · Page 2Linked to original sources
PubMed1976

Relationships between in vitro susceptibility and efficacy in experimental mouse infection-protection assay of cefazolin and cephalothin using Escherichia coli strains.

The disc sensitivity and minimal inhibitory concentrations (MIC) of cefazolin and cephalothin were compared against a series of Escherichia coli isolates. These data were correlated with the mouse protective doses of the 2 cephalosporins in animals infected with E. coli strains selected according to their various degrees of in vitro sensitivity to the 2 cephalosporins. The overwhelming majority of E. coli strains showed a significantly higher degree of susceptibility and lower MIC values for cefazolin than for cephalothin. There has been found a good correlation between the inhibition zones and especially the MIC values and the ED50 results for both cephalosporins. Using E. coli clinical isolates, cefazolin was found to be superior to cephalothin not only in vitro experiments but also more potent in protecting the experimentally infected mice.

Animals↗
PubMed1976

Orally active 7-phenylglycyl cephalosporins. Structure-activity studies related to cefatrizine (SK&F 60771).

The synthesis of a series of related broad-spectrum 7-phenylglycyl cephalosporins with 3-heterocyclicthiomethyl substituents is described. The effects of benzene-ring hydroxylation and 3-substituent variation on the in vitro antibacterial activity, height and duration of mouse serum levels, and effectiveness in protecting against bacterial infection in the mouse are examined. Included for comparison are cephalexin, cephaloglycin and their ortho-, meta- and para-hydroxy derivatives. The biological properties examined were influenced by the position of the hydroxyl group and by the nature of the 3-substituent. The 7-(p-hydroxyphenylglycyl)-3-heterocyclicthiomethyl analogs were found to produce significantly higher serum levels on oral administration to mice than their unhydroxylated counterparts. This effect was not observed with the 7-(m-hydroxyphenylglycyl)-3-heterocyclicthiomethyl cephalosporins, nor with the p-hydroxyphenylglycyl analog of cephalexin. While m- and p-hydroxylation had little effect on in vitro activity and o-hydroxyphenylglycyl cephalosporins tested had very low antibacterial activities and were not examined further. One derivative, 7-[R-2-amino-2-(4-hydroxyphenyl)acetamido]-3-(1H-1, 2, 3-triazole-4(5)-ylthiomethyl)-3-cephem-4-carboxylic acid (SK&F 60771) was found to have outstanding in vitro and in vivo activities along with oral and subcutaneous serum levels in the mouse that were significantly higher than those obtained with cephalexin. This derivative which has been given the generic name cefatrizine was selected for extensive additional biological evaluation.

Animals↗
PubMed1975

A new parenteral cephalosporin, SK&F 59962: 7-trifluoromethylthioacetamido-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid. Chemistry and structure activity relationships.

The synthesis, microbiological profile and in vivo effectiveness in laboratory animals of a series of cephalosporins having 7-acyl substituents derived from methylthioacetic acid are described. Structure-activity relationships examined include the effect of oxidation of the side-chain sulfur atom, replacement of the (side-chain) methyl hydrogens by fluorine and replacement of the 3-acetoxy substituent by thioheterocycles. One derivative, 7-trifluoromethylthioacetamido-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (SK&F 59962), was found to have outstanding antibacterial activity in vitro and in vivo.

Animals↗
PubMed1975

A new parenteral cephalosporin. SK&F 59962: in vitro and in vivo antibacterial activity and serum levels in experimental animals.

SK&F 59962, a new parenteral cephalosporin was found to have a high order of in vitro and in vivo antibacterial activity against a broad-spectrum of clinical isolates. When tested in vitro against gram-negative organisms, SK&F 59962 was consistently more active than cefazolin and far superior to cephalothin. This new antibiotic had activity equal to that of cephalothin against gram-positive bacteria. Enterobacter species were found to be susceptible to SK&F 59962. In mouse infection studies using bacterial pathogens, SK&F 59962 had protective activity of the order of that of cefazolin and superior to that of cephalothin. Following parenteral administration the serum profile of SK&F 59962 in the mouse, dog and squirrel monkey was similar to that of cephalothin. SK&F 59962 and cephalothin had lower peak serum concentrations and shorter biologic half-lives than those of cefazolin.

Animals↗
PubMed1975

Laboratory studies with cefatrizine (SK + F 60771), a new broad-spectrum orally-active cephalosporin.

Cefatrizine (SK&F 60771), a new orally-active semisynthetic cephalosporin antibiotic with broad-spectrum antibacterial activity, was compared with cephalexin and cefazolin for in vitro and in vivo antibacterial activity and pharmacokinetic behavior in laboratory animals. The average MIC values obtained with cefatrizine against gram-positive and gram-negative bacteria were superior to those obtained with cephalexin and somewhat poorer than those of cefazolin. In addition, a large percentage of the enterobacter and enterococcus isolates were found to be susceptible. Cefatrizine had a longer biological half-life and a higher peak serum level than either cefazolin or cephalexin when administered parenterally or orally to mice at 20 mg/kg. It had striking in vivo protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Hemophilus influenzae, Proteus morganii or Staphylococcus aureus reflecting its superior pharmacokinetic profile in this animal species. A variable pharmacokinetic response between animal species was observed when cefatrizine was administered either orally or parenterally to dogs, squirrel monkeys or rabbits.

Administration, Oral↗
PubMed1974

Disk susceptibility studies with cefazolin and cephalothin.

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of Escherchia coli, Enterobacter species, and Enterococcus isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity.

Cephalosporins↗
PubMed1974

Semiautomated turbidimetric microbiological assay for determination of cefazolin.

The Autoturb System, a semiautomated system for photometric bioassay, was used to determine cefazolin content. Suitable conditions for the assay using Streptococcus faecalis ATCC 10541 as the indicator organism included a medium pH of 6.0 to 7.0 and an incubation time of 3 to 3.5 h at 36 C. Multiple independent assays of samples from a common batch showed the test to be highly reproducible. Accuracy of the turbidimetric assay was evaluated by comparing data obtained from a chemical (hydroxylamine) and a biological (disk diffusion) assay. The available data show the turbidimetric assay to be a rapid, accurate, and reproducible method for determining the biological activity of cefazolin samples.

Autoanalysis↗
PubMed1974

Comparative serum levels and protective activity of parenterally administered cephalosporins in experimental animals.

Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs.

Animals↗