Prevention of Travelers' Diarrhea with Trimethoprim-Sulfamethoxazole

One hundred forty-seven students from the United States were given trimethoprim-sulfamethoxazole (TMP-SMZ; 160 mg of TMP and 800 mg of SMZ) twice daily for 21 days after their arrival in Mexico. They were watched for the development of diarrhea during the 21 days and for an additional eight days after the termination of TMP-SMZ therapy. Diarrheal illness occurred in 11 (16%) of 67 students taking TMP-SMZ and in 44 (55%) of 80 students receiving a placebo; the differences were significant (P < 0.001). Milder symptoms not quite satisfying the criteria for illness were also less common in the group receiving the active drug: 23% vs. 69% (P < 0.001). The drug appeared to prevent infection by fully virulent enterotoxigenic Escherichia coli (strains producing heat-stable toxin and those producing heat-labile toxin) and perhaps by shigella strains. During the eight days of follow-up after drug administration, 14 students (26%) who had taken TMP-SMZ and two (2.5%) who had taken the placebo experienced diarrhea (P < 0.05). Twelve subjects (14%) in the TMP-SMZ group and one subject (1%) in the placebo group developed a generalized rash that necessitated discontinuance of the drug. The eruption occurred after 9-16 days of drug administration (mean, 10 days). This study shows that TMP-SMZ taken twice daily can prevent travelers' diarrhea for up to three weeks. Diarrhea will develop, however, if the drug is stopped while the risk remains.