The Influence of Antimicrobial Agents on Total Populations of Staphylococci in Animal Tissues

Abstract

The course of experimental infection with two strains of Staphylococcus aureus during antimicrobial therapy was studied in the mouse by the microbial enumeration technique. In agreement with previous observers, it was noted that both strains of staphylococci had the capacity to induce progressive disease in the kidneys whereas they were rather rapidly reduced in census in the spleen. With one of the strains, the lungs occupied an intermediate position, and a population increase occurred in this organ whereas with the other strain, the census drop in the lungs was comparable to that in the spleen of the same animal. This distinctive pattern of behavior in the three organs was not accompanied by impressive differences in the drug susceptibilities of the population situated in the three different organs when therapy was started at the time of infection. An apparent drug antagonism was observed when penicillin was administered with other antistaphylococcal drugs in the treatment of infections induced with the penicillin-resistant Giorgio strain. When treatment was delayed until renal lesions were established, there was a decrease in the effectiveness of streptomycin and novobiocin in reducing the renal staphylocococcal populations, whereas this delay did not curb the effectiveness of penicillin, oxytetracycline or erythromycin. With all five drugs employed and with both strains of S. aureus, microbial persistence was observed throughout the 28-day period. In no instance was the infection rendered truly latent with uniformity, i.e., among all the animals in a particular experimental group. There were indications that the distinctive pattern which staphylococci displayed with respect to drug-susceptibility in vivo obtained only during the first 2 weeks of the observation period. From this point on, with the exception of the observations made in the kidneys of the delayed streptomycin- and novobiocin-treated animals, in a total 4-week experimental period, all of the microbial populations tended to fall in a similar fashion. This suggests the operation of host factors in the latter period of the experimental situation. Attempts to evoke the dormant infection, to trace the course of the persisting organisms, and to evaluate the immunogenic characteristics of the persisting organisms are in progress.