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In a double-blind clinical study, 109 adult Egyptian patients infected with Shigella spp. and 45 infected with Salmonella spp. were randomly assigned to three treatment groups: 1) norfloxacin in a single 800-mg dose, 2) norfloxacin, 400 mg twice a day for three days, and 3) trimethoprim (160 mg)-sulfamethoxazole (800 mg) (TMP-SMX), twice a day for three days. Among Shigella-infected patients, diarrheal symptoms had resolved in 86–97% and bacteriologic failure (repeat positive stool culture) occurred in only two patients five days after the start of the three treatment regimens. Among Salmonella-infected patients, diarrheal symptoms had resolved in 76–82% of patients and bacteriologic failure was common (18–36%) five days after the start of therapy. These data indicate that short-course therapy with either norfloxacin or TMP-SMX can be effectively used to treat shigellosis in adults in developing countries. However, for uncomplicated Salmonella spp. infection, short-course therapy with norfloxacin and TMP-SMX may not lead to a rapid resolution of symptoms or consistently eliminate this enteropathogen.