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Published on: March 17, 2014
Oral administration of beta-lactamase preserves colonization resistance of piperacillin-treated mice
Usha Stiefel1, Nicole J Pultz, Jaana Harmoinen
1Division of Infectious Diseases, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA. curtisd123@yahoo.com
Abstract:
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.
Insights
Oral beta-lactamase protected mice from nosocomial pathogens by inactivating piperacillin in the gut. This preserves gut microflora and prevents pathogen overgrowth during antibiotic treatment.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Antibiotic therapy, like piperacillin, can disrupt the gut microbiota, leading to a loss of colonization resistance.
- This disruption can allow opportunistic pathogens to overgrow, increasing the risk of nosocomial infections.
- Piperacillin is excreted into the intestinal tract, where it can exert antimicrobial effects on the gut flora.
Purpose of the Study:
- To investigate if orally administered beta-lactamase could protect the gut microbiota from the effects of parenteral piperacillin.
- To determine if this intervention could preserve colonization resistance against nosocomial pathogens in a mouse model.
Main Methods:
- Mice were treated with subcutaneous piperacillin, or piperacillin plus oral beta-lactamase.
- Treatment was administered 24 and 12 hours prior to orogastric inoculation with piperacillin-resistant pathogens.
- Changes in indigenous microflora and pathogen overgrowth were assessed.
Main Results:
- Oral beta-lactamase significantly reduced piperacillin-induced alterations to the indigenous gut microflora.
- The co-administration of beta-lactamase prevented the overgrowth of inoculated piperacillin-resistant pathogens.
- Colonization resistance was preserved in mice receiving both piperacillin and oral beta-lactamase.
Conclusions:
- Orally administered recombinant class A beta-lactamase effectively neutralizes intraluminal piperacillin.
- This strategy preserves gut microbiota integrity and colonization resistance during antibiotic treatment.
- Beta-lactamase offers a potential adjunctive therapy to mitigate antibiotic-associated dysbiosis and pathogen colonization.
