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

Abstract

Bacterial varients of graded antibiotic resistance were tested for their behavior toward antibiotic combinations to investigate the role played by resistance toward 1 agent in the response to a mixture of drugs. Antibiotic antagonism with a certain drug pair acting on an antibiotic-sensitive bacterial strain was not converted to synergism when the same drugs acted on an antibiotic-resistant variant. The type of combined action, whether synergism, indifference, or antagonism, was essentially stable within a given test system, although wide variations in drug concn. were necessary to demonstrate this action against bacteria of varying resistance. When "antagonistic" drug pairs were subjected to a detailed study of dosage relationships, a narrow additive zone was often found. This occurred in the range of bacteriostatic concns. of both drugs and never had the magnitude of true synergism. Synergistic test systems did not contain areas of antagonism. The relationship of these results to earlier work is discussed and factors limiting the occurrence of antibiotic antagonism in animal and human infections are summarized.