Quantitative determination of the effect of granulocytes on the course of experimental infections during antibiotic treatment

Abstract

We are presenting a quantitative determination of the effect of granulocytes, monocytes and lymphocytes on the course of infection during antibiotic treatment. The animal model was a short-term infection of the thigh muscle in normal or irradiated mice. Two kinds of antibiotics were used: tobramycin for Pseudomonas aeruginosa infections and ampicillin for Escherichia coli infections. The number of granulocytes was changed by irradiating the mice before they were infected. The dose-effect relations for both combinations of bacteria and antibiotics were determined on various days after irradiation. Analysis of the results shows that the effect of an antibiotic was predominantly potentiated by granulocytes. This means that under the conditions of granulopenia, the dose of an antibiotic must be increased to obtain the same antibacterial effect. The present results indicate that the interrelation between host factors, bacterial proliferation and antibiotic treatment can be quantitated and may offer a useful model for screening antimicrobial drugs before they are clinically applied.