Generally, reduction of colonization and infection with potentially pathogenic microorganisms in intensive care units (ICU) is attempted by a combination of antimicrobial agents administered topically in the digestive tract and systematically. We tested the efficacy of topical antimicrobial prophylaxis of the oropharynx and stomach administered in combination with sucralfate without systemic prophylaxis in 25 mechanically ventilated ICU patients. The regimen successfully reduced colonization with potentially pathogenic microorganisms in the oropharynx and trachea without modifying the intestinal flora. However, colonization and infections with gram-positive cocci and gram-negative rods other than Enterobacteriaceae and Pseudomonadaceae and resistant to one or both the antimicrobial agents used were observed.