THE ROLE OF BACTERIAL RESISTANCE IN ANTIBIOTIC SYNERGISM AND ANTAGONISM

Abstract

The combined action of paired combinations of penicillin, streptomycin, aureomycin, terramycin and chloramphenicol diluted in broth was detd. against 11 Gram-negative and Gram-positive spp. All inhibition tests were carried out at partially inhibitory concns. of the drugs and the degree of inhibition was detd. turbidimetrically. The same antibiotic pair gave either a synergistic, additive or antagonistic effect depending upon the test organism. The property of the test organism that was correlated with the pattern of the combined effect was the rate at which the bacteria became resistant to the antibiotic. When the test organism showed a marked increase in resistance within 24 hrs. to each of a pair of antibiotics the combination of such antibiotics commonly resulted in synergism. When the test organism did not show any increase in resistance within 24 hrs. to either antibiotic, synergism rarely was observed and antagonism was frequently noted. Combinations of aureomycin and terramycin by virtue of their cross resistance did not show any synergistic effect when combined. The theoretical basis and clinical implications of these results are discussed.