Due to earlier reports of the relative resistance of S. typhi and other members of the salmonella group to penicillin, and to the prevalent preoccupation of most workers with those organisms against which treatment with penicillin was more obviously applicable, little attention was payed to the chemotherapy of enteric fever until Bigger (1946) published his findings on the synergic action of a more reliable guide to the occurrence of synergism than sterilization, might be demonstrated. In conformity with the previous results, however, treated broth was also used to demonstrate synergic killing effect. Results are given in Table 12.

T455, when tested under similar conditions, was inhibited by 6·25 u./ml. penicillin and showed a twofold inhibitory synergism in the presence of sulphathiazole. It will be seen that all the strains tested showed some degree of inhibitory synergism but that, in the majority, the concentration required to inhibit growth was considerably higher than in the case of S. typhi. With the majority of strains the concentration of penicillin required to destroy the inoculum in 24 hr. at 37° C. was greater than 25 u./ml., even in the presence of sulphathiazole, while in one case no bactericidal synergism at all penicillin and sulphathiazole against S. typhi. Although, therefore, much work has been published concerning the synergic action of the sulphonamide group on penicillin activity in general, little information is available on the in vitro behaviour of the salmonellas in this respect despite the present wide, though tentative, application of the principle in the treatment of enteric fever. The experiments presented above were undertaken with the object of confirming those findings hitherto reported and of studying in detail the effects of sulphathiazole and penicillin, and of combinations of the two, on the salmonella group, with special reference to S. typhi.

For purposes of discussion it is convenient to summarize our results under the principal headings used in the text.