Faculty Collaboration Database

Ceftriaxone Administration Disrupts Intestinal Homeostasis, Mediating Noninflammatory Proliferation and Dissemination of Commensal Enterococci. Infect Immun 2018 Dec;86(12)

Date

09/19/2018

Pubmed ID

30224553

Pubmed Central ID

PMC6246901

DOI

10.1128/IAI.00674-18

Scopus ID

2-s2.0-85056802367 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Enterococci are Gram-positive commensals of the mammalian intestinal tract and harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of colonization resistance in humans by antibiotics allows enterococci to proliferate in the gut and cause disseminated infections. In this study, we used Enterococcus faecalis (EF)-colonized mice to study the dynamics of enterococci, commensal microbiota, and the host in response to systemic ceftriaxone administration. We found that the mouse model recapitulates intestinal proliferation and dissemination of enterococci seen in humans. Employing a ceftriaxone-sensitive strain of enterococci (E. faecalis JL308), we showed that increased intestinal abundance is critical for the systemic dissemination of enterococci. Investigation of the impact of ceftriaxone on the mucosal barrier defenses and integrity suggested that translocation of enterococci across the intestinal mucosa was not associated with intestinal pathology or increased permeability. Ceftriaxone-induced alteration of intestinal microbial composition was associated with transient increase in the abundance of multiple bacterial operational taxonomic units (OTUs) in addition to enterococci, for example, lactobacilli, which also disseminated to the extraintestinal organs. Collectively, these results emphasize that ceftriaxone-induced disruption of colonization resistance and alteration of mucosal homeostasis facilitate increased intestinal abundance of a limited number of commensals along with enterococci, allowing their translocation and systemic dissemination in a healthy host.

Author List

Chakraborty R, Lam V, Kommineni S, Stromich J, Hayward M, Kristich CJ, Salzman NH

Authors

Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Bacterial Agents
Bacterial Translocation
Ceftriaxone
Enterococcus faecalis
Gastrointestinal Microbiome
Gram-Positive Bacterial Infections
Homeostasis
Intestines
Male
Mice
Mice, Inbred C57BL
Symbiosis