title: Gastrointestinal colonization with a cephalosporinase-producing bacteroides species preserves colonization resistance against vancomycin-resistant enterococcus and Clostridium difficile in cephalosporin-treated mice.
abstract: Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. β-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the microbiota. Many bacteria are capable, however, of producing β-lactamase enzymes that inactivate β-lactam antibiotics. We hypothesized that prior establishment of intestinal colonization with a β-lactamase-producing anaerobe might prevent these adverse effects of β-lactam antibiotics, by inactivating the portion of antibiotic that is excreted into the intestinal tract. Here, mice with a previously abolished microbiota received either oral normal saline or an oral cephalosporinase-producing strain of Bacteroides thetaiotaomicron for 3 days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either oral administration of vancomycin-resistant Enterococcus (VRE) or sacrifice and assessment of in vitro growth of epidemic and nonepidemic strains of Clostridium difficile in murine cecal contents. Stool concentrations of VRE and ceftriaxone were measured, cecal levels of C. difficile 24 h after incubation were quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The results demonstrated that establishment of prior colonization with a β-lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone during treatment with this antibiotic, allowed recovery of the normal microbiota despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and nonepidemic strains of C. difficile in mice. These findings describe a novel probiotic strategy to potentially prevent pathogen colonization in hospitalized patients.
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA usha.stiefel@case.edu.
authors.forename: Usha
authors.initials: U
authors.lastname: Stiefel
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Nerandzic
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pultz
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D001439:Bacteroides / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D002443:Ceftriaxone / Q000378:metabolism / Q000494:pharmacology*; D002510:Cephalosporinase / Q000378:metabolism*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D015169:Colony Count, Microbial; D016983:Enterococcus / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D020459:Genes, rRNA; D051379:Mice; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D014640:Vancomycin; D002443:Ceftriaxone; D002510:Cephalosporinase