Quantitative effect of granulocytes on antibiotic treatment of experimental staphylococcal infection

Abstract

The quantitative relation between granulocytopenia and antibiotic treatment was established for a short-term Staphylococcus aureus infection in the thighs of mice, using rifampin, benzylpenicillin, and erythromycin. Granulocytopenia was induced by total-body irradiation; the number of granulocytes decreased gradually during the first 5 days after irradiation to 10% of the number in normal mice. Experimental infections were established on each of the 5 days after irradiation. In animals not treated with antibiotics, the number of granulocytes in peripheral blood and the number of CFU at the site of infection exhibited a strong negative correlation. The influence of granulocytes on the effect of antibiotics on the number of CFU differed for the three antibiotics. For erythromycin the slope of the dose-effect relation was rather flat, but a decrease in the number of granulocytes caused a significant, nearly parallel, shift in the dose-effect relation, resulting in an increase in the number of CFU. For benzylpenicillin the slope of the dose-effect relation for normal mice was also flat, but as the number of granulocytes decreased the slope became significantly steeper, resulting in a diminishing influence of granulocytes at higher dosages. For rifampin the slope of the dose-effect relation, which was already steep for nonirradiated animals, increased significantly. Here too the effect of granulocytes decreased as the dose increased.