Abstract
Traditional antimicrobial susceptibility testing completely omits pharmakologic properties of antibiotics. A model was developed which allows the investigation of kill kinetics and regrowth pattern of bacteria under the influence of fluctuating concentrations of antibiotics observed in vivo. The influence of various host defense mechanisms was studied and also the morphological changes of bacteria. Data indicate, that kill kinetics and regrowth pattern of bacteria are frequently not reflected by their MIC values.A high peak concentration seems to be less important for bacterial eradication than a long halflife of elimination. The antimicrobial activity however is best expressed by the area under the concentration curve. Rapid elimination of an antibiotic from the growth medium seems to induce the development of resistant mutants. If the halflife of an antibiotic is short, readministration in 2 - 4 hourly intervals can prevent emergence of resistant mutants. The investigation of combinations of antibiotics revealed, that different kill kinetics are seen if combination partners are administered simultaneously or in intervols. Regrowing bacteria do not express all their surface properties in the presence of subinhibitory concentrations of antibiotics; they show frequently lower surface charges than the original strain and enhanced phagocytosis. These investigations, give us information not available previously regarding the choice of rational administration schedules, optimal total daily doses and dosage intervals.
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