are very toxic to gram-positive bacteria (57, 230, 242). In enteric gram-negative bacteria, which live in the intestinal tract of animals, the outer membrane has developed into a very effective barrier, giving protection to cells from the detergent action of bile salts and degradation by digestive enzymes (207). At the same time the outer membrane of enteric and some other gram-negative bacteria acts as a strong permeability barrier to many antibiotics that are effective against other bacteria (e.g., macrolides, novobiocin, rifamycins, lincomycin, clindamycin, and fusidic acid; see reference 207). Even when the diffusion of antibiotic is merely slowed down by the presence of outer membrane, the bacteria can then inactivate the small amount of penetrating antibiotic rather than try to inactivate the almost infinite amount of antibiotic present in the medium, and thus very high levels of resistance are easily established in 1