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      Disruption of the Gut Microbiome: Clostridium difficile Infection and the Threat of Antibiotic Resistance

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          Abstract

          Clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. Central to predisposition to C. difficile infection is disruption of the gut microbiome by antibiotics. Being a Gram-positive anaerobe, C. difficile is intrinsically resistant to a number of antibiotics. Mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. While resistance to antibiotics currently used to treat C. difficile infection has not yet been detected, it may be only a matter of time before this occurs, as has been seen with other bacterial pathogens. This review will discuss C. difficile disease pathogenesis, the impact of antibiotic use on inducing disease susceptibility, and the role of antibiotic resistance and mobile elements in C. difficile epidemiology.

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          Plasmids and the spread of resistance.

          Alessandra Carattoli (2013)
          Plasmids represent one of the most difficult challenge for counteracting the dissemination of antimicrobial resistance. They contribute to the spread of relevant resistance determinants, promoting horizontal gene transfer among unrelated bacteria. Undistinguishable plasmids were identified in unrelated bacterial strains isolated at huge geographically distant area, with no apparent epidemiological links. These plasmids belong to families that are largely prevalent in naturally occurring bacteria, usually carry multiple physically linked genetic determinants, conferring resistance to different classes of antibiotics simultaneously. Plasmids also harbour virulence factors and addiction systems, promoting their stability and maintenance in the bacterial host, in different environmental conditions. The characteristics of the most successful plasmids that were at the origin of the spread of carbapenemase, expanded-spectrum β-lactamase, and plasmid-mediated quinolone resistance genes are discussed in this review. Copyright © 2013 Elsevier GmbH. All rights reserved.
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            Bile salts and glycine as cogerminants for Clostridium difficile spores.

            Joseph Sorg, Abraham Sonenshein (2008)
            Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C. difficile-associated disease. Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C. difficile spores has not been examined in detail. In an effort to understand the germination of C. difficile spores, we characterized the response of C. difficile spores to bile. We found that cholate derivatives and the amino acid glycine act as cogerminants. Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, also induced germination of C. difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C. difficile colonization mediated by the normal bacterial flora is proposed.
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              Role of hospital surfaces in the transmission of emerging health care-associated pathogens: norovirus, Clostridium difficile, and Acinetobacter species.

              David Weber, William Rutala, Melissa B. Miller … (2010)
              Health care-associated infections (HAI) remain a major cause of patient morbidity and mortality. Although the main source of nosocomial pathogens is likely the patient's endogenous flora, an estimated 20% to 40% of HAI have been attributed to cross infection via the hands of health care personnel, who have become contaminated from direct contact with the patient or indirectly by touching contaminated environmental surfaces. Multiple studies strongly suggest that environmental contamination plays an important role in the transmission of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. More recently, evidence suggests that environmental contamination also plays a role in the nosocomial transmission of norovirus, Clostridium difficile, and Acinetobacter spp. All 3 pathogens survive for prolonged periods of time in the environment, and infections have been associated with frequent surface contamination in hospital rooms and health care worker hands. In some cases, the extent of patient-to-patient transmission has been found to be directly proportional to the level of environmental contamination. Improved cleaning/disinfection of environmental surfaces and hand hygiene have been shown to reduce the spread of all of these pathogens. Importantly, norovirus and C difficile are relatively resistant to the most common surface disinfectants and waterless alcohol-based antiseptics. Current hand hygiene guidelines and recommendations for surface cleaning/disinfection should be followed in managing outbreaks because of these emerging pathogens. (c) 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Contributors
                Jonathan Iredell: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Genes (Basel)
                Journal ID (iso-abbrev): Genes (Basel)
                Journal ID (publisher-id): genes
                Title: Genes
                Publisher: MDPI
                ISSN (Electronic): 2073-4425
                Publication date (Electronic): 21 December 2015
                Publication date Collection: December 2015
                Volume: 6
                Issue: 4
                Pages: 1347-1360
                Affiliations
                Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton 3800, Australia; E-Mails: priscilla.johanesen@ 123456monash.edu (P.A.J.); kate.mackin@ 123456monash.edu (K.E.M.); melanie.hutton@ 123456monash.edu (M.L.H.); milena.awad@ 123456monash.edu (M.M.A.); sarah.larcombe@ 123456monash.edu (S.L.); jacob.amy@ 123456monash.edu (J.M.A.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: dena.lyras@ 123456monash.edu ; Tel.: +61-3-9902-9155; Fax: +61-3-9902-9222.
                Article
                Publisher ID: genes-06-01347
                DOI: 10.3390/genes6041347
                PMC ID: 4690045
                PubMed ID: 26703737
                SO-VID: 64da56ed-c32e-4292-8f41-cfd3b508a810
                Copyright © © 2015 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 August 2015
                Date accepted : 10 December 2015
                Categories
                Subject: Review

                Keywords: clostridium difficile,antibiotic-associated diarrhea,microbiome,microbiota,antibiotic resistance,mobile genetic elements
                Data availability:
                Keywords: clostridium difficile, antibiotic-associated diarrhea, microbiome, microbiota, antibiotic resistance, mobile genetic elements

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