Oral administration of penicillin, terramycin, or chloramphenicol to NCS mice rapidly brought about profound changes in their fecal flora. The lactobacilli disappeared completely, whereas the numbers of enterococci and Gram-negative bacilli reached very high levels. In contrast, no effect on the fecal flora could be detected following administration of isoniazid in any amount.
The intensity and duration of the effects on the fecal flora were related to the type of drug and to the amount of it administered. Chloramphenicol produced disturbances which were less profound and of shorter duration than those produced by penicillin or terramycin.
The duration of the disturbances in the fecal flora produced by antibacterial drugs was markedly conditioned by the nutritional regimen. The fecal flora returned to its pretreatment state (large numbers of lactobacilli, few enterococci, and few Gram-negative bacilli) within less than 4 weeks after discontinuing the drug when the mice were fed a complex diet of ill defined composition (commercial pellets). Contrariwise, the fecal flora remained markedly different from that of control mice when the animals were fed semisynthetic diets containing as source of protein either 15 per cent casein or 15 per cent wheat gluten (both supplemented with cystine); or 15 per cent wheat gluten supplemented with lysine, threonine, and cystine.
The fecal flora of mice treated with penicillin contained large numbers of lactose-fermenting Gram-negative bacilli, not found in the untreated animals. These lactose fermenters persisted for several months after discontinuance of the drug in mice fed either the casein or gluten diets, but they disappeared rapidly from mice fed pellets.
Similar results, although less striking, were obtained with Swiss mice from colonies maintained under usual conditions, and therefore having a fecal flora more complex than that of NCS mice.