Oral administration of β-lactamase preserves colonization resistance of piperacillin-treated mice

We hypothesized that orally administered, recombinant class A beta- lactamase would inactivate the portion of parenteral piperacillin excreted into the intestinal tract, preserving colonization resistance of mice against nosocomial pathogens. Subcutaneous piperacillin or piperacillin plus oral beta- lactamase were administered 24 and 12 h before orogastric inoculation of piperacillin- resistant pathogens. Oral administration of beta-lactamase reduced piperacillin- associated alteration of the indigenous microflora and prevented overgrowth of pathogens.