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Earlier studies on combined antibiotic action from this laboratory have resulted in the formulation of a scheme for combined antibiotic action. Antibiotics have been divided tentatively into two groups: I. penicillin, streptomycin, bacitracin, and neomycin; II. chloramphenicol, aureomycin, terramycin (Jawetz and Gunnison, 1952a,b; Jawetz et al., 1952). Mixtures of group I drugs often resulted in synergism, never in antagonism. Mixtures of group II drugs showed no combined effects beyond simple addition. Tue mixture of an antibiotic of group I with a drug of group II resulted in either synergism or antagonism apparently depending in part upon the sensitivity of the test bacteria to the group I drug. Thus, if the bacteria were highly sensitive to the group I antibiotic, the addition of a group II drug often interfered with the early bactericidal action of the first drug (antagonism). On the other hand, if the organisms were relatively resistant to the group I drug, in some instances the addition of a group II drug resulted in synergism, i.e., in a marked increase of early bactericidal action and the killing of greater numbers of bacteria than could be expected from simple summation of single drug effects. Most of the earlier tests were carried out with bacteria isolated from random clinical infections. Since the relative susceptibility of microorganisms to group I drugs appeared to influence the observed end result of group I + group II combined antibiotic action, it was deemed important to compare the behavior of bacterial variants of graded resistance to group I drugs when exposed to group I + group II combinations. The present paper reports such a study.

journal of bacteriology

STUDIES ON ANTIBIOTIC SYNERGISM AND ANTAGONISM: THE EFFECT IN VITRO OF COMBINATIONS OF ANTIBIOTICS ON BACTERIA OF VARYING RESISTANCE TO SINGLE ANTIBIOTICS