SYNERGISTIC ACTION OF STREPTOMYCIN WITH OTHER ANTIBIOTICS ON INTRACELLULARBRUCELLA ABORTUSIN VITRO

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Abstract
Richardson, Marvis(Michigan State University, East Lansing)and Jane N. Holt. Synergistic action of streptomycin with other antibiotics on intracellularBrucella abortusin vitro. J. Bacteriol.84:638–646. 1962.—It has been found that streptomycin acts synergistically with penicillin and tetracycline to inhibit the growth ofBrucella abortuswithin bovine cells cultured in vitro. Extracellular penicillin at 10 to 50 μg/ml was essentially bacteriostatic for intracellular brucellae. A combination of 5 to 50 μg/ml of streptomycin, which alone did not prevent the multiplication of intracellular brucellae, and 50 μg/ml of penicillin was bactericidal. Tetracycline at 0.5 to 1.0 μg/ml, which permitted growth or was bacteriostatic for brucellae within tissue cells, proved markedly bactericidal when combined with 10 μg/ml of streptomycin. Within certain limits, the synergistic effect of streptomycin and tetracycline did not appear to be a function of concentration. When the addition of streptomycin was delayed until 24 hr after the addition of tetracycline, the antibiotics acted synergistically on intracellular brucellae. To achieve intracellular synergism, five to ten times the effective extracellular concentration of streptomycin was required. Penicillin and tetracycline acted at the same concentration on extracellular and intracellular brucellae. These results suggest that tissue cell systems may prove useful for study of multiple drug therapy to be used in vivo against intracellular bacteria.