STUDIES ON ANTIBIOTIC SYNERGISM AND ANTAGONISM : Synergism among Seven Antibiotics against Various Bacteria in vitro

Abstract

In an increasing nuimber of microbial infections of man, treatment with single antibiotics fails to cure. Some of these infections, however, respond favorably to combined treatment with two antibiotic drugs. Certain pairs of these drugs have proved successful in a limited number of clinical situations. An outstand-ing example is the frequent cure of bacterial endocarditis due to enterococci by the simultaneous administration of penicillin and streptomycin, whereas neither of these drugs alone cures more than a small number of cases (Hunter, 1950; Robbins and Tompsett, 1951; Cates, Christie, and Garrod, 1951). The synergism of penicillin and streptomycin in vitro is manifested by a marked in-crease in the bactericidal rate beyond that obtainable with any concentration of either drug alone and also by the killing of the entire exposed bacterial popu-lation, a feat which neither of the two drugs can achieve alone (Jawetz, Guinnison, and Coleman, 1950; Gunnison, Jawetz, and Coleman, 1950). As more microorganisms which are resistant to certain antibiotics are encoun-tered in medical practice, there is an increased temptation to employ more than one antimicrobial drug routinely. Such indiscriminate use of two drugs is probably inadvisable inasmuch as antagonism between certain antibiotics has been dem-onstrated both in vitro and in experimental animals (Jawetz, Gunnison, Speck, and Coleman, 1951; Speck, Jawetz, and Gunnison, 1951; Jawetz, Gunnison, and Speck, 1951). To obtain a rational basis for the selection of antibiotics for com-bined therapy it is essential that the relationships among these drugs be studied. This report deals with some quantitative relationships in several synergistic combinations of antibiotics active against a number of different bacteria. The results may contribute clues to the mechanism of combined antibiotic action. An attempt has been made to answer some of the questions which arise as to the combined effect of two antibiotics in vitro