ABSTRACT. Edema disease (ED) of pigs is an enterotoxaemic disease caused by enterotoxaemic Escherichia coli (ETEEC) infection. Antimicrobial therapy for pigs with ED is controversial because it may induce death of sickish piglets. In this study, we investigated the effects in vitro of 7 antimicrobial agents, ampicillin, gentamicin, colistin, bicozamycin, fosfomycin, sulfamethoxazole-trimethoprim and enrofloxacin, on the release and production of shiga toxin (Stx) 2e by ETEEC strains. We found that more Stx 2e accumulated in the bacterial cells than was released into supernatant. Associated with inhibition of cell wall synthesis, the exposure to ampicillin or fosfomycin increased the release of Stx 2e. The production levels of Stx 2e in all antimicrobial-treated cultures were equal to the level in the control or less than in the control. These results suggest that cell wall synthesis inhibitors, such as ampicillin and fosfomycin, may change for the worse in the signs in ETEEC infectious pigs. On the other hand, gentamicin, colistin, bicozamycin and enrofloxac in may be useful for the treatment of pigs with ED. KEY WORDS: antimicrobia, edema disease, enterotoxaemic Escherichia coli, shiga toxin 2e, swine.J. Vet. Med. Sci. 66(8): 899-903, 2004 Edema disease (ED) of the pig has been found throughout the world since ED was first reported in Ireland in 1938 [17]. ED has been a sporadically occurring disease found mainly in post-weaned piglets that causes systemic vascular damage as a result of intestinal infection with shiga toxinproducing Escherichia coli (STEC) [1,2,5]. The STEC is also called enterotoxaemic Escherichia coli (ETEEC) [14]. After ETEEC colonizes in the intestines, shiga toxin (Stx) 2e produced by the ETEEC is absorbed into the capillary vessels and then damages the endothelial cells [1,2,5]. The manifestations of ED include palpebral edema, neurological impairment, lateral recumbence and sudden death [1,2]. The speed of onset and severity of clinical signs and gross pathological lesions are related to the dose of the toxin. Intervals between injection and onset of the disease vary from 7 to 28 hr, the mean time to death being from 24 to 42 hr [2]. Classical ED has been seen to occur sporadically and subside spontaneously [1,2,8,11]. Recently, ED has tended to persist and spread, causing great economic damage to pig farmers [20,21,24].Antimicrobial administration has been used as one of the most common treatments for the eradication of STEC from the intestines of humans and animals [12,14,16,22]. Nevertheless, some antimicrobial agents have been reported to increase the release of Stxs from enterohemorrhagic Escherichia coli (EHEC) associated with enterohemorrhagic colitis and hemolytic uremic syndrome of humans in vitro [4,10,13,22,23]. In ED affected farms, deaths of piglets associated with antimicrobial treatment have increased in number [7,24]. Until now, however, there has been no investigation to determine the effect of antimicrobial agents on the production and release of Stx 2e by ETEEC.In ...