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S W Chapman

Publications and source records attributed to S W Chapman.

59 records · Page 4Linked to original sources
PubMed1983

Staphylococcal beta-lactamase and efficacy of beta-lactam antibiotics: in vitro and in vivo evaluation.

The susceptibility of five cephalosporins and nafcillin to changes in inoculum size of 26 isolates of Staphylococcus aureus was studied. The spectrum of antibiotic sensitivity to such changes was cefazolin = cephaloridine greater than cefamandole greater than cephalothin greater than cefoxitin = nafcillin. Half of the isolates resulted in large and half in minimal inoculum-induced changes in minimal inhibitory concentrations (MICs). These changes correlated with the amount of beta-lactamase produced by the isolates. The in vivo relevance of these findings was studied in a model of intraperitoneal infection in mice. The effect of beta-lactamase production on mortality was greatest among animals given cefazolin or cephaloridine, intermediate among those given cefamandole, and nonexistent among those given cefoxitin, cephalothin, or nafcillin. The number of organisms in the animals' spleens paralleled survival rates. An increase in the serum level of cefazolin increased the survival rate among mice given that drug. Hence, the survival of mice was influenced by (1) the ability of the infecting organism to increase the MIC of an antibiotic via inoculum increases, (2) the sensitivity of the antibiotic to beta-lactamase, and (3) the peak level of antibiotic attained in serum.

Animals↗
PubMed1983

Inhibition by ketoconazole of mitogen-induced DNA synthesis and cholesterol biosynthesis in lymphocytes.

The effects of ketoconazole on mitogen-induced DNA synthesis and cholesterol biosynthesis in human and murine lymphocytes have been examined. Ketoconazole concentrations which do not affect cell viability (0.1 to 10 micrograms/ml) in culture led to a dose-dependent inhibition of DNA synthesis, as measured by [3H]thymidine incorporation, induced by either T-cell or B-cell mitogens. At drug concentrations 5- to 10-fold lower, ketoconazole inhibited the incorporation of [14C]acetate into cholesterol, with a resultant accumulation of [14C]lanosterol. The suppressive effects of ketoconazole on DNA synthesis were reversed by increasing the concentration of human serum in the culture medium from 5 to 20%. The depletion of lipoproteins in human serum by density centrifugation reduced the cholesterol content by 90% but did not affect the ability of the serum to overcome the inhibition by ketoconazole of DNA synthesis. Unlike DNA synthesis, cholesterol biosynthesis was not restored by 20% fresh human serum or lipoprotein-depleted human serum. These results demonstrate that ketoconazole potently inhibits DNA synthesis and cholesterol synthesis in mitogen-stimulated lymphocytes at drug concentrations obtained therapeutically. Further, the uncoupling of endogenous cholesterol synthesis and DNA synthesis indicates at least two levels of action of ketoconazole in mammalian lymphocytes.

Animals↗
PubMed1980

Method of reliable determination of minimal lethal antibiotic concentrations.

The lack of a standardized, statistically reliable method for in vitro determinations of the minimal lethal or bactericidal concentrations of antibiotics has complicated analyses of isolates of Staphylococcus aureus which appear to be inhibited but not killed by the usual concentrations of cell wall-active antibiotics. We describe a method which identifies some of the covariants involved in determinations of minimal lethal concentrations. Lethality was defined as a 99.9% reduction in the initial inoculum of bacteria after 24 h of incubation. We limited the sample volume to 0.01 ml to minimize the inhibitory effect of antibiotic and corresponding rejection values, which detected lethality with a high degree of sensitivity and specificity. When the number of colonies on subculture was equal to or less than the rejection value, the antibiotic was considered lethal for the test organism. Rejection values encompassed initial inocula from 10(5) to 10(7) colony-forming units per ml for single and duplicate samples and allowed for 1 or 5% variability in pipette volumes and errors in initial inoculum determinations. This method was used to determine the minimal lethal concentrations of semi-synthetic penicillins for S. aureau isolates, one of which was tolerant to the killing action of penicillin.

Anti-Bacterial Agents↗