Oral Administration of b-Lactamase Preserves Colonization Resistance of Piperacillin-Treated Mice

We hypothesized that orally administered, recombinant class A b-lactamase would inactivate the portion of parenteral pi-peracillin excreted into the intestinal tract, preserving colo-nization resistance of mice against nosocomial pathogens. Sub-cutaneous piperacillin or piperacillin plus oral b-lactamase were administered 24 and 12 h before orogastric inoculation of piperacillin-resistant pathogens. Oral administration of b-lactamase reduced piperacillin-associated alteration of the in-digenous microflora and prevented overgrowth of pathogens. Indigenous intestinal microflora inhibit the growth of poten-tially pathogenic microorganisms [1]. This defense mechanism, termed “colonization resistance, ” can be markedly diminished by antibiotics that are excreted into the intestinal tract [1–3], predisposing individuals to colonization and infection with community-acquired pathogens, such as Salmonella species [4]