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Biomedical subjects

L Phillips

Publications and source records attributed to L Phillips.

At least 181 records · Page 10Linked to original sources

Antimicrobial activity of SK&F 88070, an expanded-spectrum cephalosporin with high and prolonged levels in blood.

SK&F 88070 (7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3- [[[1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio] methyl]-3-cephem-4-carboxylic acid) is a new parenteral cephalosporin with an expanded-spectrum profile of antibacterial activity, including activity against Pseudomonas aeruginosa, and with high and prolonged levels in sera of experimental animals. The activity of SK&F 88070 was compared with those of cefotaxime and other cephalosporins against more than 500 clinical isolates in vitro by microtiter twofold dilution tests in Mueller-Hinton broth. SK&F 88070 was extremely potent against all of the members of the family Enterobacteriaceae that were tested, including beta-lactamase-producing strains. Its activity against P. aeruginosa was comparable to those of cefotaxime, ceftizoxime, and moxalactam. SK&F 88070 was less potent than cefotaxime or ceftizoxime against Staphylococcus species but was comparable to moxalactam. It had in vivo activity against the same Bacteroides strains as did cefotaxime, although it was less potent. Both SK&F 88070 and cefotaxime had less activity when tested with high inoculum levels of most of the rarer gram-negative bacteria. There was a greater decrease in the activity of SK&F 88070 than of cefotaxime in the presence of human serum, reflecting the higher degree of binding of SK&F 88070 to serum proteins. SK&F 88070 had peak levels and half-lives in serum much greater than those of cefotaxime in experimental animals after parenteral administration. In mouse protection studies, SK&F 88070 was more effective than cefotaxime against gram-negative bacteria but less effective than cefotaxime against Staphylococcus aureus.

Animals↗

Activity of ceftizoxime and comparative compounds against Bacteroides fragilis in a mouse model of anaerobic infection.

A new mouse model of anaerobic infection with Bacteroides fragilis alone or in a mixed infection with Escherichia coli is described. It is established by implantation under the skin of a filter paper disk saturated with the appropriate bacterial suspension. The penetration of antibiotics into the implantation site can be detected by assaying the disk. The local infection can be both standardized and evaluated by determining the bacterial count on the disk. The antimicrobial efficacy of ceftizoxime was compared with other commercially available antibiotics administered in a single dose, 40 mg/kg subcutaneously, one hour after implantation of the disk. Using such a regimen ceftizoxime was found to be superior to a clindamycin-gentamicin combination and equal to or superior to cefoxitin in these models.

Animals↗

Antibody to hepatitis B surface antigen in nonprimate animal species.

The hepatitis B virus infects only humans and higher apes. Viruses similar to the human hepatitis B virus (hepadna viruses) have been discovered in several nonprimate species including woodchucks, ground squirrels, and domesticated ducks. To search for other models of hepatitis B virus infection, we screened serum specimens from 64 exotic animals (24 species), 56 domesticated animals (6 species), and 52 laboratory animals (3 species). Samples were tested for deoxyribonucleic acid polymerase by enzymatic assay and for hepatitis B surface antigen and antibody and antibody to hepatitis B core antigen by radioimmunoassays. All sera were negative for deoxyribonucleic acid polymerase, hepatitis B surface antigen, and antibody to hepatis B core antigen suggesting that none of these animals harbored hepadna viruses in serum. However, 48% of the sera from 58% of the 33 species were reactive for antibody to hepatitis B surface antigen. This reactivity was blocked by human serum positive for hepatitis B surface antigen but not by control human serum. The antibody to hepatitis B surface antigen was generally present in low titer (95% were less than or equal to 1:16) and was often directed against subdeterminants of hepatitis B surface antigen (anti-d, anti-y, or anti-w). Characterization of the antibody to hepatitis B surface antigen by gel chromatography, sucrose density ultracentrifugation, affinity chromatography, and chemical inactivation suggested that it was entirely or predominantly immunoglobulin M antibody. Thus, many animals species have naturally occurring immunoglobulin M antibody to hepatitis B surface antigen detectable by radioimmunoassay. This antibody could arise as a result of either the intermittent spontaneous maturation of clones of antibody to hepatitis B surface antigen forming lymphocytes or exposure to environmental antigens that share epitopes with hepatitis B surface antigen. Similar naturally occurring antibody to hepatitis B surface antigen may be present in some humans.

Animal Population Groups↗

Gonococcal pelvic inflammatory disease: case-finding observations.

During a 20 month period, 110 women with gonococcal pelvic inflammatory disease an 165 women with uncomplicated gonorrhea were provided intensive case-finding services (interviewing of patients and tracing of contacts). Approximately three contacts per case were investigated, and 24.3% of the 859 male contacts were infected. Nearly two thirds (64.6%) of the infected contacts were asymptomatic. Active public health intervention was frequently necessary to persuade asymptomatic men to seek medical attention; removal of these men from the disease pool may serve to prevent reinfection of treated women and to diminish the transmission of gonorrhea.

Colorado↗

Focused interviewing in gonorrhea control.

To develop an operational approach to the identification of high risk gonorrhea transmitters, three groups of women infected with Neisseria gonorrhoeae (recent repeaters, routine discoveries, and women with pelvic inflammatory disease) were offered intensive casefinding services during an 18-month period. Approximately three contacts per case were investigated, and 27.4% of the contacts were infected. Of infected contracts, 61% were asymptomatic. Asymptomatic, remote contacts to these women appear to be important in the continuing transmission of gonorrhea. The interviewing approach used reflected that employed in syphilis (thorough, detailed, and long) rather than the more casual interviews usually employed for gonorrhea patients. During this period, gonorrhea morbidity declined 22%. Further exploration of a targeted approach to gonorrhea epidemiology is indicated.

Adolescent↗

In vitro and in vivo laboratory studies on three hydroxyiminophenylacetyl cephalosporins with particular reference to SK&F 80303, an unusually long-acting cephalosporin.

Three cephalosporins with 7-(2-hydroxyiminophenylacetamido) side chains (SK&F 79433, 80000 and 80303), differing in their 3-substituents, exhibited similar broad-spectrum antibacterial activity in vitro against strains of Staphylococcus aureus, Streptococcus faecalis and various Gram-negative bacilli. All three were active in vivo (s.c., mouse) against S. aureus, Escherichia coli or Klebsiella pneumoniae, but they differed significantly in serum pharmacokinetic profiles. SK&F 80303 produced high and extremely prolonged serum levels and protected mice when administered up to 24 hours prior to challenge with beta-lactamase-producing S. aureus or K. pneumoniae. It was resistant to hydrolysis by beta-lactamases from S. aureus, and variably so to beta-lactamases from E. coli strains. SK&F 80303 was bacteriolytic to logarithmically growing S. aureus, E. coli, Proteus mirabilis, K. pneumoniae and Enterobacter cloacae (partially). SK&F 80303 illustrates further the effect of the 3-sulfoalkyltetrazole substituent on the pharmacokinetic properties of cephalosporins. Its combined biological properties make it a possible candidate for therapeutic and long-term prophylactic use.

Animals↗

SK&F 75073, new parenteral broad-spectrum cephalosporin with high and prolonged serum levels.

SK&F 75073, a new parenteral cephalosporin, was found to have broad in vitro and in vivo antibacterial activity including isolates usually resistant to cephalothin and cefazolin. This activity included indole-positive Proteus and Enterobacter species and some Serratia isolates. Proteus mirabilis strains were particularly susceptible, as were Haemophilus influenzae and Neisseria species. The activity of SK&F 75073 against gram-positive bacteria was poorer than that of the control cephalosporins. This cephalosporin is highly bound to serum proteins, and a loss in in vitro activity was observed in the presence of serum. Parenteral administration of SK&F 75073 to experimental animals (mice, dogs, squirrel monkeys) resulted in high and prolonged serum levels when compared with cefazolin and other injectable cephalosporins. This favorable serum profile was reflected in the excellent protection observed in mice infected with pathogenic bacteria.

Animals↗

Semisynthetic cephalosporins with antifungal activity: laboratory studies on 2-pyridinethiol 1-oxide cephalosporins.

Cephalosporins are chemotherapeutic agents whose spectrum and use are limited to antibacterial activity. Therefore, it was of interest to find several new semisynthetic cephalosporins which possess in vitro antifungal activity against Trichophyton mentagrophytes, Candida albicans and certain other yeasts. Five new cephalosporins containing the 2-pyridinethiol 1-oxide grouping were examined. Four with this heterocyclic moiety in the 3-position were found to have activity. One with the grouping in the 7-acyl-side chain was inactive. The degree of the antifungal activity was influenced by the substituent at the 7-position. The cephalosporin with a p-hydroxyphenylglycyl side chain was the most potent against the fungal strains studied. Despite this in vitro antifungal activity, none of the compounds protected mice against a systemic Candida albicans infection. All of these cephalosporins had broad spectrum in vitro and in vivo antibacterial activity.

Animals↗