Objective: To evaluate the clinical and microbiologic efficacy and safety of norfloxacin for acute diarrhea.
Design: Double-blind, placebo-controlled, randomized clinical multicenter trial.
Setting: Six departments of infectious disease.
Participants: Patients 12 years of age or older with a history of acute diarrhea lasting 5 or fewer days. Eighty-five percent of patients (511/598) were evaluable for efficacy. Of these evaluable patients, 70% had traveled abroad within the previous 6 weeks.
Interventions: Patients received either norfloxacin, 400 mg, or placebo twice daily for 5 days.
Measurements: Enteric pathogens were isolated in 51% of the evaluable patients: Campylobacter species in 29%, Salmonella species in 16%, Shigella species in 3.5%, and other pathogens in 2.6%.
Results: Norfloxacin had a favorable overall effect compared with placebo (cure rate, 63% compared with 51%; P = 0.003). There were statistically favorable effects in culture-positive patients, patients with salmonellosis, and severely ill patients but not in culture-negative patients or patients with campylobacteriosis or shigellosis. A significant difference was noted between norfloxacin and placebo in median time to cure among all evaluable patients (3 compared with 4 days, P = 0.02) and in patients with campylobacteriosis (3 compared with 5 days, P = 0.05) but not in patients. Culture-positive, but not culture-negative patients, in the norfloxacin group had significantly fewer loose stools per day compared with patients in the placebo group from day 2 onward (P less than or equal to 0.01). Norfloxacin was significantly less effective than placebo in eliminating Salmonella species on days 12 to 17 (18% compared with 49%, P = 0.006), whereas the opposite was true for Campylobacter species (70% compared with 50%, P = 0.03). In six of nine patients tested, norfloxacin-resistant Campylobacter species (MIC, greater than or equal to 32 micrograms/mL) appeared after norfloxacin treatment.
Conclusion: Empiric treatment reduced the intensity and, to some extent, the duration of symptoms of acute diarrhea. The effect was restricted to patients who had bacterial enteropathogens or who were severely ill. The clinical usefulness of this treatment is limited by the fact that norfloxacin seems to delay the elimination of salmonella and to induce resistance in campylobacter.