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  1. Article ; Online: The changing faces of Clostridium difficile: a personal reflection of the past 34 years.

    Poxton, Ian R

    Anaerobe

    2013  Volume 24, Page(s) 124–127

    Abstract: Late in 1978 my boss gave me a folder with "Clostridium difficile (diffikilé)" written on it. Inside were a few recent and now classic papers by Bartlett, Larson and co. It was suggested that this might be an interesting research topic. So began a ... ...

    Abstract Late in 1978 my boss gave me a folder with "Clostridium difficile (diffikilé)" written on it. Inside were a few recent and now classic papers by Bartlett, Larson and co. It was suggested that this might be an interesting research topic. So began a continuing adventure which has resulted in at least 50 publications from my group. Over the years we have made several important contributions to the field. Beginning in 1982 we showed that C. difficile was a common cause of community-acquired infection! During the next few years we did extensive structural studies on the bacterium. This culminated in 1984 with a fingerprinting study (by immunoblotting surface antigens), on Swedish strains supplied by Carl-Erik Nord, which was probably the first study to demonstrate that C. difficile was really an infectious agent. This was later reinforced with strains sent from Amsterdam by Ed Kuijper. Later in the 1980s, in a study of recurrent disease, we showed that ca. 50% of recurrences were due to infection with a different strain. During my term as chair of the European Study Group for C. difficile, we began to define the status of C. difficile infection (CDI) in Europe and develop guidance for diagnosis and treatment. Recently we utilised our extensive culture collection, with isolates from the 1970s to the present, to observe how epidemiology has been driven largely by antibiotic usage. We have now come full circle: in the early years C. difficile infection was caused by many different strains. Then in the period beginning in the 1990s, characterised by often-large outbreaks and poor infection control, disease was caused by a few endemic strains highlighted by the 027/NAP1/BI pandemic. Now in a much-improved local situation, we are seeing again that the majority of cases (largely sporadic) is caused by multiple types. Current studies range from molecular studies on toxin and spore production, immune responses, novel observations on CDI in children, to what is the best way of decontaminating the anaerobe laboratory.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Biomedical Research/history ; Clostridium Infections/epidemiology ; Clostridium Infections/history ; Clostridium Infections/microbiology ; Clostridium difficile/drug effects ; Clostridium difficile/genetics ; Clostridium difficile/isolation & purification ; Europe ; Evolution, Molecular ; Genetic Variation ; History, 20th Century ; History, 21st Century ; Humans ; Microbiology/history ; Molecular Epidemiology
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2013-12
    Publishing country England
    Document type Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1237621-8
    ISSN 1095-8274 ; 1075-9964
    ISSN (online) 1095-8274
    ISSN 1075-9964
    DOI 10.1016/j.anaerobe.2012.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Fidaxomicin: a new macrocyclic, RNA polymerase-inhibiting antibiotic for the treatment of Clostridium difficile infections.

    Poxton, Ian R

    Future microbiology

    2010  Volume 5, Issue 4, Page(s) 539–548

    Abstract: Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these ... ...

    Abstract Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these regions. With the emergence of a hypervirulent, endemic strain, more severe disease is being recognized and is occurring in previously considered unusual patient groups. Vancomycin and metronidazole are the current mainstays for therapy of severe and nonsevere disease, respectively. Relapse is a major concern, with treatment options for these cases often difficult. Any new drug must be better than vancomycin for severe disease with fewer relapses. Fidaxomicin, a macrocyclic RNA polymerase inhibitor, has a narrow spectrum of activity, which is almost C. difficile specific. This drug appears to have a higher clinical cure rate than vancomycin, and fewer patients relapse following initial treatment. From the results of a recent Phase III trial, fidaxomicin appears to be an extremely promising drug for treating C. difficile infection and preventing relapses.
    MeSH term(s) Aged ; Aminoglycosides/pharmacology ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/antagonists & inhibitors ; Clinical Trials as Topic ; Clostridium difficile/drug effects ; Cross Infection/drug therapy ; DNA-Directed RNA Polymerases/antagonists & inhibitors ; Enterocolitis, Pseudomembranous/drug therapy ; Humans ; Secondary Prevention ; Treatment Outcome ; Vancomycin/therapeutic use
    Chemical Substances Aminoglycosides ; Anti-Bacterial Agents ; Bacterial Proteins ; Vancomycin (6Q205EH1VU) ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; lipiarmycin (Z5N076G8YQ)
    Language English
    Publishing date 2010-04
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1746-0921
    ISSN (online) 1746-0921
    DOI 10.2217/fmb.10.20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Clostridium difficile.

    Poxton, Ian R

    Journal of medical microbiology

    2008  Volume 57, Issue Pt 6, Page(s) 683–684

    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Clostridium Infections/epidemiology ; Clostridium Infections/microbiology ; Clostridium difficile/drug effects ; Clostridium difficile/pathogenicity ; Clostridium difficile/physiology ; Drug Resistance, Multiple, Bacterial ; Humans ; Virulence
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2008-06
    Publishing country England
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 218356-0
    ISSN 1473-5644 ; 0022-2615
    ISSN (online) 1473-5644
    ISSN 0022-2615
    DOI 10.1099/jmm.0.2008/002451-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clostridium difficile--special collection.

    Rupnik, Maja / Poxton, Ian R

    Journal of medical microbiology

    2013  Volume 62, Issue Pt 9, Page(s) 1368

    MeSH term(s) Animals ; Clostridium difficile/pathogenicity ; Clostridium difficile/physiology ; Enterocolitis, Pseudomembranous/diagnosis ; Humans ; International Cooperation ; Spores, Fungal/growth & development
    Language English
    Publishing date 2013-08-14
    Publishing country England
    Document type Congress ; Editorial
    ZDB-ID 218356-0
    ISSN 1473-5644 ; 0022-2615
    ISSN (online) 1473-5644
    ISSN 0022-2615
    DOI 10.1099/jmm.0.065425-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Generation of Markerless Deletions in the Nosocomial Pathogen

    Theophilou, Elena-Stella / Vohra, Prerna / Gallagher, Maurice P / Poxton, Ian R / Blakely, Garry W

    Applied and environmental microbiology

    2019  Volume 85, Issue 3

    Abstract: Clostridium ... ...

    Abstract Clostridium difficile
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Clostridioides difficile/genetics ; Clostridioides difficile/metabolism ; Cross Infection/microbiology ; DNA Breaks, Double-Stranded ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Gene Deletion ; Genetic Techniques ; Homologous Recombination ; Humans ; Mutagenesis ; Mutation
    Chemical Substances Bacterial Proteins ; DNA, Bacterial
    Language English
    Publishing date 2019-01-23
    Publishing country United States
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 223011-2
    ISSN 1098-5336 ; 0099-2240
    ISSN (online) 1098-5336
    ISSN 0099-2240
    DOI 10.1128/AEM.02055-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Proceedings from the 3rd International Clostridium difficile Symposium 2010, September 22-24, 2010, Bled, Slovenia.

    Poxton, Ian R / Rupnik, Maja

    Journal of medical microbiology

    2011  Volume 60, Issue Pt 8, Page(s) 1055–1056

    MeSH term(s) Animals ; Clostridium Infections ; Clostridium difficile ; Enterocolitis, Pseudomembranous ; Humans
    Language English
    Publishing date 2011-09-08
    Publishing country England
    Document type Congress ; Overall
    ZDB-ID 218356-0
    ISSN 1473-5644 ; 0022-2615
    ISSN (online) 1473-5644
    ISSN 0022-2615
    DOI 10.1099/jmm.0.033985-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Induction of cytokines in a macrophage cell line by proteins of Clostridium difficile.

    Vohra, Prerna / Poxton, Ian R

    FEMS immunology and medical microbiology

    2012  Volume 65, Issue 1, Page(s) 96–104

    Abstract: Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins produced by C. difficile are responsible for the characteristic pathology observed in C. difficile disease, but several surface-associated proteins of C. difficile are also ... ...

    Abstract Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins produced by C. difficile are responsible for the characteristic pathology observed in C. difficile disease, but several surface-associated proteins of C. difficile are also recognized by the immune system and could modulate the immune response in infection. The aim of this study was to assess the induction of cytokines in a macrophage cell line in response to different antigens prepared from five C. difficile strains: the hypervirulent ribotype 027, ribotypes 001 and 106 and reference strains VPI 10463 and 630 (ribotype 012). PMA-activated THP-1 cells were challenged with surface-layer proteins, flagella, heat-shock proteins induced at 42 and 60 °C and culture supernatants of the five C. difficile strains. The production of the pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8 and IL-12p70 was observed in response to the surface-associated proteins, and high levels of TNF-α, IL-1β and IL-8 were detected in response to challenge with culture supernatants. The immune response triggered by the surface-associated proteins was independent of the strain from which the antigens were derived, suggesting that these proteins might not be related to the varying virulence of the hypervirulent ribotype 027 or ribotypes 001 and 106. There was no interstrain difference observed in response to the culture supernatants of the tested C. difficile strains, but this was perhaps due to toxicity induced in the macrophages by large amounts of toxin A and toxin B.
    MeSH term(s) Antigens, Bacterial/immunology ; Bacterial Proteins/immunology ; Cell Line ; Clostridium difficile/immunology ; Culture Media/chemistry ; Cytokines/secretion ; Humans ; Macrophages/immunology ; Macrophages/microbiology
    Chemical Substances Antigens, Bacterial ; Bacterial Proteins ; Culture Media ; Cytokines
    Language English
    Publishing date 2012-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1143208-1
    ISSN 1574-695X ; 0928-8244
    ISSN (online) 1574-695X
    ISSN 0928-8244
    DOI 10.1111/j.1574-695X.2012.00952.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Molecular techniques in the diagnosis and management of infectious diseases: do they have a role in bacteriology?

    Poxton, Ian R

    Medical principles and practice : international journal of the Kuwait University, Health Science Centre

    2005  Volume 14 Suppl 1, Page(s) 20–26

    Abstract: The diagnosis and management of bacterial diseases has been done by traditional methods for a century or more. With the advent of molecular methods, however, these traditional approaches are being challenged. This review examines the pros and cons of ... ...

    Abstract The diagnosis and management of bacterial diseases has been done by traditional methods for a century or more. With the advent of molecular methods, however, these traditional approaches are being challenged. This review examines the pros and cons of traditional versus modern methods and tries to answer the question: when are molecular methods useful or essential? The following topics are addressed with appropriate examples: diagnosis; identification, typing and fingerprinting; pathogenesis; patient management; susceptibility to disease, and resistance to antimicrobial agents. It was concluded that there is still a place for both traditional and modern molecular methods, and training of staff must include both methodologies. Innovation is encouraged--but new technologies must be thoroughly tested before introduction into the routine lab. Liaison between laboratory scientist and physician is important, but above all experience is paramount.
    MeSH term(s) Bacteriology/trends ; Communicable Diseases/diagnosis ; Communicable Diseases/genetics ; Communicable Diseases/therapy ; Drug Resistance, Microbial/genetics ; Genetic Predisposition to Disease ; Genetics, Microbial/trends ; Humans ; Molecular Diagnostic Techniques/methods ; Molecular Diagnostic Techniques/trends ; Polymerase Chain Reaction ; Polymorphism, Genetic
    Language English
    Publishing date 2005
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 645108-1
    ISSN 1423-0151 ; 1011-7571
    ISSN (online) 1423-0151
    ISSN 1011-7571
    DOI 10.1159/000086181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Comparison of toxin and spore production in clinically relevant strains of Clostridium difficile.

    Vohra, Prerna / Poxton, Ian R

    Microbiology (Reading, England)

    2011  Volume 157, Issue Pt 5, Page(s) 1343–1353

    Abstract: Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins that it produces (TcdA and TcdB) are responsible for the characteristic pathology of C. difficile infection (CDI), while its spores persist in the environment, causing its ... ...

    Abstract Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins that it produces (TcdA and TcdB) are responsible for the characteristic pathology of C. difficile infection (CDI), while its spores persist in the environment, causing its widespread transmission. Many different strains of C. difficile exist worldwide and the epidemiology of the strains is ever-changing: in Scotland, PCR ribotype 012 was once prevalent, but currently ribotypes 106, 001 and 027 are endemic. This study aimed to identify the differences among these ribotypes with respect to their growth, and toxin and spore production in vitro. It was observed that the hypervirulent ribotype 027 produces significantly more toxin than the other ribotypes in the exponential and stationary phases of growth. Further, the endemic strains produce significantly more toxins and spores than ribotype 012. Of note was the observation that tcdC expression did not decrease into the stationary phase of growth, implying that it may have a modulatory rather than repressive effect on toxin production. Further, the increased expression of tcdE in ribotype 027 suggests its importance in the release of the toxins. It can thus be concluded that several genotypic and phenotypic traits might synergistically contribute to the hypervirulence of ribotype 027. These observations might suggest a changing trend towards increased virulence in the strains currently responsible for CDI.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Toxins/biosynthesis ; Clostridium difficile/genetics ; Clostridium difficile/growth & development ; Clostridium difficile/metabolism ; Enterocolitis, Pseudomembranous/microbiology ; Gene Expression Regulation, Bacterial ; Humans ; Spores, Bacterial/genetics ; Spores, Bacterial/growth & development ; Spores, Bacterial/metabolism
    Chemical Substances Bacterial Proteins ; Bacterial Toxins
    Language English
    Publishing date 2011-02-17
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.046243-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Efficacy of decontaminants and disinfectants against Clostridium difficile.

    Vohra, Prerna / Poxton, Ian R

    Journal of medical microbiology

    2011  Volume 60, Issue Pt 8, Page(s) 1218–1224

    Abstract: Clostridium difficile is a common nosocomial pathogen transmitted mainly via its spores. These spores can remain viable on contaminated surfaces for several months and are resistant to most commonly used cleaning agents. Thus, effective decontamination ... ...

    Abstract Clostridium difficile is a common nosocomial pathogen transmitted mainly via its spores. These spores can remain viable on contaminated surfaces for several months and are resistant to most commonly used cleaning agents. Thus, effective decontamination of the environment is essential in preventing the transmission of C. difficile in health-care establishments. However, this emphasis on decontamination must also be extended to laboratories due to risk of exposure of staff to potentially virulent strains. Though few cases of laboratory-acquired infection have been reported, the threat of infection by C. difficile in the laboratory is real. Our aim was to test the efficacy of four disinfectants, Actichlor, MicroSol 3+, TriGene Advance and Virkon, and one laboratory decontaminant, Decon 90, against vegetative cells and spores of C. difficile. Five strains were selected for the study: the three most commonly encountered epidemic strains in Scotland, PCR ribotypes 106, 001 and 027, and control strains 630 and VPI 10463. MICs were determined by agar dilution and broth microdilution. All the agents tested inhibited the growth of vegetative cells of the selected strains at concentrations below the recommended working concentrations. Additionally, their effect on spores was determined by exposing the spores of these strains to different concentrations of the agents for different periods of time. For some of the agents, an exposure of 10 min was required for sporicidal activity. Further, only Actichlor was able to bring about a 3 log(10) reduction in spore numbers under clean and dirty conditions. It was also the only agent that decontaminated different hard, non-porous surfaces artificially contaminated with C. difficile spores. However, this too required an exposure time of more than 2 min and up to 10 min. In conclusion, only the chlorine-releasing agent Actichlor was found to be suitable for the elimination of C. difficile spores from the environment, making it the agent of choice for the decontamination of laboratory surfaces.
    MeSH term(s) Clostridium difficile/drug effects ; Decontamination/methods ; Disinfectants/pharmacology ; Drug Resistance, Bacterial ; Spores, Bacterial/drug effects
    Chemical Substances Disinfectants
    Language English
    Publishing date 2011-04-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218356-0
    ISSN 1473-5644 ; 0022-2615
    ISSN (online) 1473-5644
    ISSN 0022-2615
    DOI 10.1099/jmm.0.030288-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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