Emergence of high-level trimethoprim resistance in fecal Escherichia coli during oral administration of trimethoprim or trimethoprim--sulfamethoxazole

N Engl J Med. 1982 Jan 21;306(3):130-5. doi: 10.1056/NEJM198201213060302.


The effect of daily administration of trimethoprim (TMP), trimethoprim--sulfamethoxazole (TMP--SMX), or placebo on aerobically grown fecal gram-negative bacteria was monitored in 136 students from the United States during a two-week diarrhea-prevention study in Mexico. Unlike patients in other studies with these agents, who had urinary-tract infection or granulocytopenia, most persons in this study had no change in total fecal Enterobacteriaceae and had high-level TMP and SMX resistance in virtually all these strains. Escherichia coli was the predominant TMP-resistant organism isolated; 96 per cent of 165 TMP-resistant Esch. coli isolates were resistant to at least four antimicrobial agents, and 25 per cent were resistant to seven. TMP resistance was transferable in 40 ot 100 strains tested. Despite the lack of TMP resistance in other studies of prophylaxis, our results clearly demonstrate the remarkable capacity for emergence and dissemination of resistance to this agent.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Diarrhea / prevention & control
  • Drug Combinations
  • Drug Resistance, Microbial
  • Escherichia coli / drug effects*
  • Feces / microbiology
  • Humans
  • Sulfamethoxazole / pharmacology*
  • Travel
  • Trimethoprim / pharmacology*


  • Anti-Bacterial Agents
  • Drug Combinations
  • Trimethoprim
  • Sulfamethoxazole