Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 23, 2026.

Clostridium difficile – From Colonization to Infection

Holger Schäffler, Anne Breitrück

Frontiers in Microbiology · 2018 · Review

doi:10.3389/fmicb.2018.00646

Abstract

Clostridium difficile (C. difficile) is the most frequent cause of nosocomial antibiotic-associated diarrhea. The incidence of C. difficile infection (CDI) has been rising worldwide with subsequent increases in morbidity, mortality and health care costs. Asymptomatic colonization with C. difficile is common and a high prevalence has been found in specific cohorts, e.g. hospitalized patients, adults in nursing homes and in infants. However, the risk of infection with C. difficile differs significantly between these cohorts. While CDI is a clear indication for therapy, colonization with C. difficile is not believed to be a direct precursor for CDI and therefore does not require treatment. Antibiotic therapy causes alterations of the intestinal microbial composition, enabling C. difficile colonization and consecutive toxin production leading to disruption of the colonic epithelial cells. Clinical symptoms of CDI range from mild diarrhea to potentially life-threatening conditions like pseudomembranous colitis or toxic megacolon. While antibiotics are the still the treatment of choice for CDI, new therapies have emerged in recent years such as antibodies against C. difficile toxin B and fecal microbial transfer (FMT). This specific therapy for CDI underscores the role of the indigenous bacterial composition in the prevention of the disease in healthy individuals and its role in the pathogenesis after alteration by antibiotic treatment. In addition to the pathogenesis of CDI, this review focuses on the colonization of C. difficile in the human gut and factors promoting CDI.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Clostridium difficile was first described as part of the intestinal bacterial composition in newborns in 1935. In the 1970s, C. difficile was identified as the causative agent for pseudomembranous colitis following antibiotic therapy. The pathogenic potential of this strain was proven to fulfill the Koch’s postulates underscoring its role in the development of CDI. Recently, a dramatic increase in the incidence as well as in the mortality of CDI could be observed worldwide.

The clinical spectrum of C. difficile ranges from asymptomatic colonization, mild and self-limiting disease to a severe, life-threatening pseudomembranous colitis, toxic megacolon, sepsis and death. CDI is defined when there is the presence of symptomatic diarrhea defined by three or more unformed stools per 24 h and at least one of the following criteria: a positive laboratory assay for C. difficile toxin A and/or B or toxin-producing C. difficile organism in a stool sample or pseudomembranous colitis or colonic histopathology characteristics of CDI revealed by endoscopy. CDI is associated with an increased abundance of toxin-producing C. difficile strains, leading to high toxin concentrations within the colon resulting in inflammation and damage of the colonocytes. Usually, the indigenous microbial communities provide a colonization resistance to C. difficile, which could also be proven in animal models. However, a disruption of this microbial system can promote the development of CDI.

While the clinical presentation of CDI is distinctive, C. difficile colonization without any symptoms, defined as asymptomatic colonization is common, especially in neonates. This review focuses on the role of C. difficile in asymptomatic colonization and CDI to better understand which factors might contribute to the progression and also prevention of the disease.

Microbiology

C. difficile is a Gram-positive, anaerobic, spore-forming and toxin-producing bacillus, belonging to cluster XI the Clostridium genus and can be isolated from water, vegetables, hospital environment, and the intestines of humans and domesticated animals.

Different virulence factors are associated with the development of CDI. The most important virulence factor is the release of multiple toxins, namely large glycosylating exotoxins A (TcdA) and B (TcdB). These toxins lead to the characteristic clinical symptoms by binding to C. difficile toxin receptors on intestinal epithelial cells. Another toxin can be found in some C. difficile strains, especially the PCR ribotype 027, named binary toxin or C. difficile transferase, which is associated with a higher mortality rate in patients. This ribotype 027 carries a deletion in tcdC, which is discussed to play a major role in its increased production of toxins. There are C. difficile strains which can synthesize C. difficile transferase in the absence of TcdA and TcdB. These toxins, which are encoded on the pathogenicity locus, are multi-domain toxins with glycosyltransferase activities, which transfer glycosyl residues to small Ras homologous GTPases and consecutively lead to a loss of the intestinal membrane integrity and to cell death. As a consequence, inflammation of the colon occurs with massive fluid loss into the large intestine, clinically presenting as acute diarrhea. While initially TcdA was suggested to play a more prominent role in the development of CDI compared to TcdB, this view was challenged by different other studies. Colonization with C. difficile occurs by oral ingestion of spores from infected individuals or the environment. While C. difficile is an anaerobic organism, C. difficile spores can survive in aerobic environments for months or years. C. difficile spores are resistant to the gastric acid and can germinate into vegetative cells in the anaerobic conditions of the colon.

Epidemiology of CDI

The worldwide incidence of CDI has been rising steadily since 2000, however, susceptibility to treatment decreased. C. difficile was first reported to cause severe antibiotic-associated diarrhea and pseudomembranous colitis in the 1970s and has become the most common healthcare-associated infection, leading to about 500,000 cases and 29,000 deaths annually in the United States. Overall, the epidemiology data of CDI in Europe are more variable due to different reporting systems within the European Union. However, by extrapolation of the data from the United Kingdom to Europe, they result in a total number of 172,000 CDI cases annually within the European Union. The epidemic spread of hypervirulent C. difficile strains, e.g., PCR ribotype 027 leads to larger nosocomial outbreaks, which are associated with increased morbidity and mortality. The economic impact of CDI is enormous, leading to additional medical costs of over one billion dollar per year in the United States and three billion euro per year within the European Union. Especially hospitalized patients and adults in long-term care facilities are at a higher risk of developing CDI. Additionally, in infants an increase of CDI was observed in the last decade. This is especially interesting since – as mentioned above – C. difficile is highly prevalent in infants, however, they usually do not show clinical signs of CDI. Nevertheless, the data regarding CDI in pediatric patients are limited.

Asymptomatic Colonization

While many studies have focused on the pathogenesis and the development of CDI, the role of asymptomatic C. difficile colonization and its progression to CDI is still not completely understood. While in the past literature the definition of asymptomatic C. difficile colonization is not uniform, were proposing one as followed: either detectable concentrations of C. difficile or its toxin and the absence of diarrhea without colonoscopic or histopathologic findings consistent with pseudomembranous colitis.

The prevalence of asymptomatic C. difficile colonization in adults varies in different population groups. In healthy adults, several studies have shown that 0–17.5% were colonized by C. difficile strains without clinical signs of CDI. The colonization rate of toxigenic strains ranges from 1 to 5% in the surveyed group. While the prevalence of asymptomatic C. difficile colonization is relatively low in healthy adults, it can rise dramatically in individuals having contact with the health system. Elderly in long-term care facilities or nursing homes have an increased rate of colonization range from 0 to 51%. A high prevalence of asymptomatic C. difficile can also be found in patients or health-care workers. Additionally, patients in rehabilitation centers have an increased rate of asymptomatic C. difficile colonization. Furthermore, a high percentage of asymptomatic C. difficile colonization can be found in adult patients with underlying diseases, e.g., cystic fibrosis.

Risk factors for the development of the last asymptomatic C. difficile colonization are hospitalization within 12 months, use of corticosteroids, a previous history of CDI and antibodies against toxin B.

In contrast to adults, a high prevalence of C. difficile colonization without clinical signs of CDI can be observed in infants and neonates. Especially in the first 4 weeks of life, C. difficile colonization increases from 0% to an average of 37%, followed by a recovery, dropping to an average of 10% during the first year of life. Colonization rates comparable to the rates in healthy adults were observed in infants by the age of 2. Analysis of ribotypes revealed that pediatric patients harbor several toxigenic strains that circulate in adult patients.

Although – according to the definition – asymptomatic colonized individuals show no clinical signs of CDI, they can act as a reservoir of C. difficile and also may serve as potential disease carriers and might therefore transmit C. difficile to others. Furthermore, asymptomatic colonization with C. difficile is a crucial factor in the progression to CDI, as carriers of toxigenic strains are at a higher risk for the development of an infection compared to non-colonized patients.

In contrast to this, asymptomatic colonization could also induce the production of antibodies, which in turn protect their host against CDI with a humoral immune response. It was also proposed that asymptomatic C. difficile colonization might lead to the integration of C. difficile into the indigenous intestinal microbiota, serving as a protective factor for the development of CDI. This theory could also be proven in hamsters, where colonization with a non-toxigenic C. difficile strain before the application of a toxigenic C. difficile strain was able to prevent the development of CDI. However, further prospective studies to better understand the mechanisms how individuals develop asymptomatic C. difficile colonization and if this may act as risk or protective factor in the progression for an infection are needed.

From Colonization to Infection

A schematic overview which factors lead to the development of CDI is given in Figure 1.

The Indigenous Microbiota

The intestinal microbiota is a complex ecosystem consisting of over a thousand bacterial species reaching its highest concentration in the colon. In adults, a healthy intestinal microbiota is dominated by the phyla Bacteroidetes and Firmicutes and shows a high diversity and richness. These commensal bacteria are essential for the host metabolism, nutrition function, maturation of the immune system and protection against pathogens. During human lifetime, different factors, such as the mode of delivery, diet, geography, antibiotic use and the development of gastrointestinal diseases can influence the composition of the intestinal microbiota. A disruption of this ecosystem, a so-called intestinal dysbiosis can have a significant influence on the structure and the function of the resident microbiota. Changes of the indigenous intestinal microbial composition result in a breakdown of the colonization resistance, which favors C. difficile germination, growth and spreading within the intestine.

It is well known that the susceptibility of CDI is strongly associated with a previous exposure to antibiotics. The application of antibiotics, especially broad-spectrum antibiotics, can have profound and long-lasting consequences on the host by altering the intestinal bacterial composition and the metabolome. The first description of CDI in the setting of antibiotic therapy was in 1974 in a patient after the application of clindamycin. Other antibiotics, especially cephalosporins, penicillin and fluoroquinolones have also been reported to be associated with the development of CDI. Moreover, it has been demonstrated that cumulative exposure to any kind of antibiotics increases the risk of developing CDI. The impact of antibiotic administration on the microbial composition in healthy adults has been studied extensively. summarized the effects of different antimicrobial agents on the bacterial diversity and single bacterial phylae, families and classes. The effects of antibiotics on the intestinal microbial composition can also be investigated in murine models, allowing the examination of factors which lead to the resistance of C. difficile colonization and subsequent development of CDI. Different studies described the intestinal microbial composition in patients with CDI and observed similar results regarding a reduced diversity and also reduced species richness. In contrast to healthy controls, patients with CDI showed an increase in Firmicutes and Proteobacteria phyla and a decrease in Bacteroidetes phylum. Furthermore, Ruminococcacea, Lachnospiraceae, Bacteriodaceae, Clostrida cluster IV and XIVa are decreased while an increased abundance of Enterococacea could be observed. Additionally, in a study by, ), co-colonization with potentially protective bacterial taxa, e.g., Clostridiales Family XI Incertae Sedis, Clostridium or Eubacterium may protect the development of CDI from asymptomatic C. difficile colonization. In a recent study by, Veillonella dispar was found as a candidate organism which might be protective for the recurrence of C. difficile.

Bile Acids

Germination of C. difficile spores is supported by changes in the composition of bile acids. A reduced number of bacteria, producing hydrolase enzymes, results in a reduction of secondary bile acids, which normally inhibit vegetative cell growth and a simultaneous increase of primary bile acids like cholate or taurocholic acid stimulates spore germination. While cholate and glycine can promote C. difficile spore formation, chenodeoxycholate was found to act as an inhibitor of spore formation. A depletion of commensals can also result in an oversupply of available nutrients, e.g., monosaccharides, which can further be utilized by C. difficile. In a murine model, administration of antibiotics led to a shift of the bile acid pool and therefore increased C. difficile spore germination.

Bacteriocins

Bacteriocins are ribosomally synthesized antimicrobial peptides with narrow or broad spectrum activity against other bacterial species. The secretion of bacteriocins from Bacillus, Lactococcus, and Enterococcus strains, whose antimicrobial function against C. difficile has been proven in vitro, is decreased in CDI.

C. Difficile Toxin A Receptor

The susceptibility of the host to CDI is also associated with the presence or absence of C. difficile toxin A receptor on the surface of intestinal epithelial cells. This fact was reinforced by the study of which compared the effect of toxin A in newborn compared to adult rabbit ileum. The absence of pathological effects in the newborn ileum may be due to a complete lack or only a low expression of C. difficile toxin A receptor and therefore might prevent neonates from the development a CDI.

Immunological Factors

It is well known that the host recognition of C. difficile and the subsequent innate and adaptive immune responses have a protective effect against the development of CDI. tested prospectively the immune response of the host via measuring IgG antibodies of TcdA and found that an acquired antibody response to C. difficile protected against CDI. However, the antibody response to C. difficile did not affect asymptomatic C. difficile colonization.

The protective effect of high IgA concentrations, which is a potent toxin A neutralizer has also been shown in breastfeed infants. The presence of maternal secretory IgA may prevent them from colonization, as this cohort was found to have lower recovery rates compared to formula-fed infants. However, beneath IgA also other components of breast milk have the potential to bind C. difficile toxin A.

Bacterial Factors

The development of CDI is closely linked to the bacterial virulence factors TcdA and TcdB and the binary toxin, as non-toxigenic C. difficile strains are not known to cause CDI. Colonization with hypervirulent ribotype NAP1 occurred more likely in CDI than in asymptomatic colonized individuals, due to an increased TcdA and TcdB production compared to other toxigenic ribotypes.

Extrinsic Risk Factors

Different studies indicate that – beneath host-mediated and pathogen-related factors – multiple extrinsic risk factors increase the development and also severity of CDI.

Antibiotics

As described above, the use of antibiotics is the most-common risk factor in the development of CDI. Antibiotics have dramatic effects on the bacterial ecosystem of the gut, which can last for a long period of time. Especially fluoroquinolones and particularly cephalosporins and clindamycin are associated with an increased frequency of CDI.

Proton Pump Inhibitors

Another important risk factor for the development of CDI is the use of proton pump inhibitors (PPIs). While the normal gastric acidity provides a protective host defense, an increase of the gastric pH may prevent the gastric content from an elimination of the ingested C. difficile spores. However, the role of PPIs in the development of CDI is still controversial, since other studies could not prove an association between the gastric acid suppression and an increased risk for the development of CDI. Since the use of PPIs is increasing globally, further prospective studies are needed in order to address the possible association with these drugs and the development of asymptomatic C. difficile colonization or CDI.

Health Care Facilities

In hospitals or long-term care facilities, an increased exposure to C. difficile can be found due to high C. difficile contamination on surfaces, medical devices and health care personal or infected roommates. Furthermore, a high rate of polypharmacy like antibiotics and underlying co-morbidities such as malignancy or inflammatory bowel disease are closely associated with patients in health care facilities. To decrease the C. difficile transmission and infection rate in hospitals and long-term care facilities, a screening of new patients could be an option to identify toxigenic strain carriers and isolate them from other patients. These approach was able to significantly decrease the incidence of hospital acquired CDI in a prospective Canadian study cohort.

Age

Clostridium difficile is more common in advanced age, also showing a more severe outcome in this population. There are several possible mechanisms for this phenomenon. First, an inadequate innate or humoral immune response might lead to a higher incidence and also severity of CDI. Secondarily, the higher prevalence of CDI in the elderly could also be associated with the change of the intestinal microbial composition, e.g., loss of bacterial diversity during aging, which might promote C. difficile colonization. Additionally, the presence of chronic disorders and an increase in the infection rate, requiring polypharmacy, including antibiotics, is generally much higher in this age cohort.

C. difficile in Food

While the transmission of C. difficile from humans to humans is well-established, C. difficile as a foodborne disease still remains a matter of debate. In different studies, C. difficile was found in retail meat. Additionally, C. difficile was also detected in water, vegetables, pets and also piglets. Regular exposure to C. difficile in the food might lead to asymptomatic C. difficile colonization. However, since community-acquired C. difficile is relatively uncommon, it is not clear if the ingestion of C. difficile via the oral route also leads to consecutive CDI. Further studies will be needed in order to address this issue.

Conventional

The mainstay in the treatment of CDI is – beneath the withdrawal of antibiotics fostering CDI – the initiation of an antibiotic therapy, e.g., vancomycin or metronidazole. Recent advances in the therapy of C. difficile and the role of antibiotic resistance in CDI are summarized elsewhere. However, therapy of recurrent CDI can be challenging with conventional antibiotic therapy. Recurrence of CDI is found in 20–30% of the patients with a high mortality rate in this cohort. Fidaxomicin, approved by the United States Food and Drug Administration for CDI treatment, shows reduced recurrence rates in patients with C. difficile, however, not in the highly virulent strains B1/NAP1/027. In a recent study, the use of bezlotoxumab, a human monoclonal antibody against TcdB, was associated with a lower rate of C. difficile recurrent infection compared to placebo. The addition of an antibody against TcdA (actoxumab) had no effect on the disease recurrence alone or in combination with bezlotoxumab, which is also underscoring the crucial role of toxin B in the pathogenesis of CDI. A matter of debate for this new approach is the potential combination with fecal microbial transplantation (FMT). Further studies will be needed in order to redefine the treatment algorithm of CDI with bezlotoxumab.

Microbiota-Targeted Therapy

The intestinal microbial communities of patients with CDI differ from patients with asymptomatic C. difficile colonization. In different studies, the administration of single strain probiotics showed only limited success in the treatment of CDI. The role of probiotics in the prevention of CDI is still discussed controversial. In contrast to this, the probiotic treatment with three strains from Lactobacillus parallel to antibiotic application in hospitalized adults showed a significantly decreased CDI rate from 18.0 to 2.3 cases per 10,000 patients-days during the 10-year observation period. The most direct and effective way in changing the patient’s intestinal bacterial composition is via FMT. FMT is highly effective in the treatment of antibiotic-refractory CDI and recently was also shown to be cost effective. FMT involves installation of stool from a healthy donor into a patient, leading to a shift of the intestinal microbial communities. Despite the high effectiveness of FMT in the treatment of recurrent CDI, the long-term effects of this therapeutic approach are still not known and might lead to an increased risk of other diseases. Furthermore, FMT is still a highly diverse biological product with several challenges in the standardization of protocols. Another therapeutic approach is the administration of non-toxigenic C. difficile strains or a mixture of spore-forming commensals. In two phase II clinical trials testing both treatments, a significant decrease of CDI recurrence was observed. However, in another study it was observed that non-toxigenic strains had the capacity to change their phenotype to toxigenic C. difficile strains. Therefore, non-toxigenic strains can also be a predisposition in the development of CDI and have to be used with caution in the setting of C. difficile prevention.

Conclusion

The incidence of CDI increased dramatically in the last years. While asymptomatic C. difficile colonization is common especially in newborns, the progression from asymptomatic colonization to infection is not completely understood and large, prospective studies are lacking. While many studies in adults and infants showed high C. difficile colonization rates with toxigenic as well as non-toxigenic strains, the detection of C. difficile or its toxins in feces of individuals does not immediately implicate an infection with this pathogen and therefore treatment is only indicated when there are clinical signs of CDI. Although persons with asymptomatic C. difficile colonization are potential disease carriers and therefore predispose a risk factor for themselves and other people, based on current information an eradication of C. difficile is not indicated. CDI is strongly associated with host-mediated factors, including the indigenous microbiota, bacteriocins, toxin A receptor and immunological factors as well as pathogen-related factors, including TcdA, TcdB, and binary toxin. However, host-mediated factors are discussed to have a more pronounced role in the development of CDI. Especially a disruption of the indigenous intestinal microbial composition within the host can promote the development of CDI via germination and proliferation of toxigenic C. difficile strains. Furthermore, several external factors like age, polypharmacy or underlying medical conditions increase the risk and severity of CDI. Due to the strong association between CDI and antibiotic exposure, therapeutic approaches that target the modulation of the intestinal bacterial composition like FMT are crucial in this clinical setting. Treatment strategies with non-toxigenic C. difficile strains are on their way, however, a change of non-toxigenic to toxigenic C. difficile strains can occur, making this therapeutic approach challenging.

The role of asymptomatic C. difficile colonization in the development of CDI is still a controversial matter of debate. Further studies elucidating the clinical consequences of asymptomatic C. difficile colonization are needed to further investigate if the presence of C. difficile without any signs of CDI is beneficial or might potentially be harmful. We conclude that mechanisms that enable the progression from asymptomatic C. difficile colonization to CDI are closely associated with host-mediated as well as pathogen-related factors and a combination of both might be of outstanding interest in the pathogenesis and also prevention of CDI.

Author’s Note

Due to a limitation of words no citation of all primary literature was possible, the authors kindly ask to excuse this circumstance.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 208

  1. 1.

    Akhtar A. J. Shaheen M. (2007 ). Increasing incidence of Clostridium difficile-associated diarrhea in African-American and Hispanic patients: association with the use of proton pump inhibitor therapy. J. Natl. Med. Assoc. 99 500–504.

    Not in our library

  2. 2.

    al Saif N. Brazier J. S. (1996 ). The distribution of Clostridium difficile in the environment of South Wales. J. Med. Microbiol. 45 133–137.

    Not in our library10.1099/00222615-45-2-133

  3. 3.

    Alasmari F. Seiler S. M. Hink T. Burnham C.-A. D. Dubberke E. R. (2014 ). Prevalence and risk factors for asymptomatic Clostridium difficile carriage. Clin. Infect. Dis. 59 216–222.

    Not in our library10.1093/cid/ciu258

  4. 4.

    Ananthakrishnan A. N. (2011 ). Clostridium difficile infection: epidemiology, risk factors and management. Nat. Rev. Gastroenterol. Hepatol. 8 17–26.

    Not in our library10.1038/nrgastro.2010.190

  5. 5.

    Antharam V. C. Li E. C. Ishmael A. Sharma A. Mai V. Rand K. H. (2013 ). Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J. Clin. Microbiol. 51 2884–2892.

    Not in our library10.1128/jcm.00845-13

  6. 6.

    Antonopoulos D. A. Huse S. M. Morrison H. G. Schmidt T. M. Sogin M. L. Young V. B. (2009 ). Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect. Immun. 77 2367–2375.

    Not in our library10.1128/iai.01520-08

  7. 7.

    Antunes L. C. M. Finlay B. B. (2011 ). A comparative analysis of the effect of antibiotic treatment and enteric infection on intestinal homeostasis. Gut Microbes 2 105–108.

    Not in our library10.4161/gmic.2.2.15610

  8. 8.

    Arbel L. T. Hsu E. McNally K. (2017 ). Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: a literature review. Cureus 9:e1599.

    Not in our library10.7759/cureus.1599

  9. 9.

    Aronsson B. Möllby R. Nord C. E. (1985 ). Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiological data from Sweden, 1980-1982. J. Infect. Dis. 151 476–481.

    Not in our library10.1093/infdis/151.3.476

  10. 10.

    Arvand M. Moser V. Schwehn C. Bettge-Weller G. Hensgens M. P. Kuijper E. J. (2012 ). High prevalence of Clostridium difficile colonization among nursing home residents in Hesse, Germany. PLoS One 7:e30183.

    Not in our library10.1371/journal.pone.0030183

  11. 11.
    Binary Toxin and Death after Clostridium difficile Infection · 2011
    No notice
  12. 12.

    Bacon A. E. Fekety R. Schaberg D. R. Faix R. G. (1988 ). Epidemiology of Clostridium difficile colonization in newborns: results using a bacteriophage and bacteriocin typing system. J. Infect. Dis. 158 349–354.

    Not in our library10.1093/infdis/158.2.349

  13. 13.

    Bagdasarian N. Rao K. Malani P. N. (2015 ). Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 313 398–408.

    Not in our library10.1001/jama.2014.17103

  14. 14.

    Bakri M. M. Brown D. J. Butcher J. P. Sutherland A. D. (2009 ). Clostridium difficile in ready-to-eat salads, Scotland. Emerg. Infect. Dis. 15 817–818.

    Not in our library10.3201/eid1505.081186

  15. 15.

    Barbut F. Cornely O. A. Fitzpatrick F. Kuijper E. J. Nagy E. Rupnik M. (2013 ). Clostridium difficile Infection in Europe: A CDI Europe Report. Available at: http://www.multivu.com/assets/60637/documents/60637-CDI-HCP-Report-original.pdf [accessed March 05 2018].

    Not in our library

  16. 16.

    Bartlett J. G. (2006 ). Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann. Intern. Med. 145 758–764.

    Not in our library10.7326/0003-4819-145-10-200611210-00008

  17. 17.

    Bartlett J. G. (2010 ). Clostridium difficile: progress and challenges. Ann. N. Y. Acad. Sci. 1213 62–69.

    Not in our library10.1111/j.1749-6632.2010.05863.x

  18. 18.

    Bartlett J. G. Chang T. W. Onderdonk A. B. (1978 ). Comparison of five regimens for treatment of experimental clindamycin-associated colitis. J. Infect. Dis. 138 81–86.

    Not in our library10.1093/infdis/138.1.81

  19. 19.

    Bartlett J. G. Onderdonk A. B. Cisneros R. L. Kasper D. L. (1977 ). Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J. Infect. Dis. 136 701–705.

    Not in our library10.1093/infdis/136.5.701

  20. 20.

    Bartoloni A. Mantella A. Goldstein B. P. Dei R. Benedetti M. Sbaragli S. (2004 ). In-vitro activity of nisin against clinical isolates of Clostridium difficile. J. Chemother. 16 119–121.

    Not in our library10.1179/joc.2004.16.2.119

  21. 21.

    Bauer M. P. Farid A. Bakker M. Hoek R. A. S. Kuijper E. J. van Dissel J. T. (2014 ). Patients with cystic fibrosis have a high carriage rate of non-toxigenic Clostridium difficile. Clin. Microbiol. Infect. 20 O446–O449.

    Not in our library10.1111/1469-0691.12439

  22. 22.

    Bauer M. P. Notermans D. W. van Benthem B. H. B. Brazier J. S. Wilcox M. H. Rupnik M. (2011 ). Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377 63–73.

    Not in our library10.1016/s0140-6736(10)61266-4

  23. 23.

    Bavishi C. Dupont H. L. (2011 ). Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment. Pharmacol. Ther. 34 1269–1281.

    Not in our library10.1111/j.1365-2036.2011.04874.x

  24. 24.

    Begley M. Hill C. Gahan C. G. M. (2006 ). Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 72 1729–1738.

    Not in our library10.1128/aem.72.3.1729-1738.2006

  25. 25.

    Blaser M. J. (2014 ). The microbiome revolution. J. Clin. Invest. 124 4162–4165.

    Not in our library10.1172/jci78366

  26. 26.

    Bolton R. P. Tait S. K. Dear P. R. Losowsky M. S. (1984 ). Asymptomatic neonatal colonisation by Clostridium difficile. Arch. Dis. Child. 59 466–472.

    Not in our library10.1136/adc.59.5.466

  27. 27.

    Borriello S. P. Honour P. Turner T. Barclay F. (1983 ). Household pets as a potential reservoir for Clostridium difficile infection. J. Clin. Pathol. 36 84–87.

    Not in our library10.1136/jcp.36.1.84

  28. 28.
    Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers · 2013
    No notice
  29. 29.

    Buffie C. G. Bucci V. Stein R. R. McKenney P. T. Ling L. Gobourne A. (2015 ). Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517 205–208.

    Not in our library10.1038/nature13828

  30. 30.

    Buffie C. G. Jarchum I. Equinda M. Lipuma L. Gobourne A. Viale A. (2012 ). Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect. Immun. 80 62–73.

    Not in our library10.1128/iai.05496-11

  31. 31.

    Buonomo E. L. Petri W. A. (2016 ). The microbiota and immune response during Clostridium difficile infection. Anaerobe 41 79–84.

    Not in our library10.1016/j.anaerobe.2016.05.009

  32. 32.

    Campbell R. R. Beere D. Wilcock G. K. Brown E. M. (1988 ). Clostridium difficile in acute and long-stay elderly patients. Age Ageing 17 333–336.

    Not in our library10.1093/ageing/17.5.333

  33. 33.

    Carroll K. C. Bartlett J. G. (2011 ). Biology of Clostridium difficile: implications for epidemiology and diagnosis. Annu. Rev. Microbiol. 65 501–521.

    Not in our library10.1146/annurev-micro-090110-102824

  34. 34.

    Chang J. Y. Antonopoulos D. A. Kalra A. Tonelli A. Khalife W. T. Schmidt T. M. (2008 ). Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197 435–438.

    Not in our library10.1086/525047

  35. 35.

    Chang V. T. Nelson K. (2000 ). The role of physical proximity in nosocomial diarrhea. Clin. Infect. Dis. 31 717–722.

    Not in our library10.1086/314030

  36. 36.

    Chen X. Katchar K. Goldsmith J. D. Nanthakumar N. Cheknis A. Gerding D. N. (2008 ). A mouse model of Clostridium difficile-associated disease. Gastroenterology 135 1984–1992.

    Not in our library10.1053/j.gastro.2008.09.002

  37. 37.

    Cheng S. H. Lu J. J. Young T. G. Perng C. L. Chi W. M. (1997 ). Clostridium difficile–associated diseases: comparison of symptomatic infection versus carriage on the basis of risk factors, toxin production, and genotyping results. Clin. Infect. Dis. 25 157–158.

    Not in our library10.1086/516891

  38. 38.

    Clooten J. Kruth S. Arroyo L. Weese J. S. (2008 ). Prevalence and risk factors for Clostridium difficile colonization in dogs and cats hospitalized in an intensive care unit. Vet. Microbiol. 129 209–214.

    Not in our library10.1016/j.vetmic.2007.11.013

  39. 39.

    Cohen S. H. Gerding D. N. Johnson S. Kelly C. P. Loo V. G. McDonald L. C. (2010 ). Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect. Control Hosp. Epidemiol. 31 431–455.

    Not in our library10.1086/651706

  40. 40.

    Cornely O. A. Crook D. W. Esposito R. Poirier A. Somero M. S. Weiss K. (2012 ). Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect. Dis. 12 281–289.

    Not in our library10.1016/s1473-3099(11)70374-7

  41. 41.

    Cotter P. D. Hill C. Ross R. P. (2005 ). Bacteriocins: developing innate immunity for food. Nat. Rev. Microbiol. 3 777–788.

    Not in our library10.1038/nrmicro1273

  42. 42.

    Cowardin C. A. Petri W. A. (2014 ). Host recognition of Clostridium difficile and the innate immune response. Anaerobe 30 205–209.

    Not in our library10.1016/j.anaerobe.2014.08.014

  43. 43.

    Curry S. R. Marsh J. W. Muto C. A. O’Leary M. M. Pasculle A. W. Harrison L. H. (2007 ). tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile. J. Clin. Microbiol. 45 215–221.

    Not in our library10.1128/jcm.01599-06

  44. 44.

    Curry S. R. Muto C. A. Schlackman J. L. Pasculle A. W. Shutt K. A. Marsh J. W. (2013 ). Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin. Infect. Dis. 57 1094–1102.

    Not in our library10.1093/cid/cit475

  45. 45.

    De Filippo C. Cavalieri D. Di Paola M. Ramazzotti M. Poullet J. B. Massart S. (2010 ). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. U.S.A. 107 14691–14696.

    Not in our library10.1073/pnas.1005963107

  46. 46.

    Debast S. B. Bauer M. P. Kuijper E. J. (2014 ). European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin. Microbiol. Infect. 20(Suppl. 2), 1–26.

    Not in our library10.1111/1469-0691.12418

  47. 47.

    Deshpande A. Pant C. Pasupuleti V. Rolston D. D. K. Jain A. Deshpande N. (2012 ). Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin. Gastroenterol. Hepatol. 10 225–233.

    Not in our library10.1016/j.cgh.2011.09.030

  48. 48.
    The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing · 2008
    No notice
  49. 49.

    Dethlefsen L. Relman D. A. (2011 ). Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl. Acad. Sci. U.S.A. 108(Suppl. 1), 4554–4561.

    Not in our library10.1073/pnas.1000087107

  50. 50.

    Dial S. Alrasadi K. Manoukian C. Huang A. Menzies D. (2004 ). Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 171 33–38.

    Not in our library10.1503/cmaj.1040876

  51. 51.

    Dominguez-Bello M. G. Costello E. K. Contreras M. Magris M. Hidalgo G. Fierer N. (2010 ). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. U.S.A. 107 11971–11975.

    Not in our library10.1073/pnas.1002601107

  52. 52.

    Drudy D. Fanning S. Kyne L. (2007 ). Toxin A-negative, toxin B-positive Clostridium difficile. Int. J. Infect. Dis. 11 5–10.

    Not in our library10.1016/j.ijid.2006.04.003

  53. 53.

    Dubberke E. R. Olsen M. A. (2012 ). Burden of Clostridium difficile on the healthcare system. Clin. Infect. Dis. 55(Suppl. 2), S88–S92.

    Not in our library10.1093/cid/cis335

  54. 54.

    Dupuy B. Govind R. Antunes A. Matamouros S. (2008 ). Clostridium difficile toxin synthesis is negatively regulated by TcdC. J. Med. Microbiol. 57 685–689.

    Not in our library10.1099/jmm.0.47775-0

  55. 55.

    Eglow R. Pothoulakis C. Itzkowitz S. Israel E. J. O’Keane C. J. Gong D. (1992 ). Diminished Clostridium difficile toxin A sensitivity in newborn rabbit ileum is associated with decreased toxin A receptor. J. Clin. Invest. 90 822–829.

    Not in our library10.1172/jci115957

  56. 56.

    Eyre D. W. Griffiths D. Vaughan A. Golubchik T. Acharya M. O’Connor L. (2013 ). Asymptomatic Clostridium difficile colonisation and onward transmission. PLoS One 8:e78445.

    Not in our library10.1371/journal.pone.0078445

  57. 57.

    Fekety R. Shah A. B. (1993 ). Diagnosis and treatment of Clostridium difficile colitis. JAMA 269 71–75.

    Not in our library10.1001/jama.1993.03500010081036

  58. 58.
    Asymptomatic Clostridium difficile colonization: epidemiology and clinical implications · 2015
    No notice
  59. 59.

    Gao L. Maidment I. Matthews F. E. Robinson L. Brayne C. (2018 ). Medication usage change in older people (65+) in England over 20 years: findings from CFAS I and CFAS II. Age Ageing 47 220–225.

    Not in our library10.1093/ageing/afx158

  60. 60.

    Garibaldi R. A. Nurse B. A. (1986 ). Infections in the elderly. Am. J. Med. 81 53–58.

    Not in our library10.1016/0002-9343(86)90514-0

  61. 61.

    Gerding D. N. Johnson S. Peterson L. R. Mulligan M. E. Silva J. (1995 ). Clostridium difficile-associated diarrhea and colitis. Infect. Control Hosp. Epidemiol. 16 459–477.

    Not in our library10.2307/30141083

  62. 62.

    Gerding D. N. Johnson S. Rupnik M. Aktories K. (2014 ). Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance. Gut Microbes 5 15–27.

    Not in our library10.4161/gmic.26854

  63. 63.

    Gerding D. N. Meyer T. Lee C. Cohen S. H. Murthy U. K. Poirier A. (2015 ). Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 313 1719–1727.

    Not in our library10.1001/jama.2015.3725

  64. 64.

    Gerding D. N. Muto C. A. Owens R. C. (2008 ). Measures to control and prevent Clostridium difficile infection. Clin. Infect. Dis. 46(Suppl. 1), S43–S49.

    Not in our library10.1086/521861

  65. 65.

    Geric B. Carman R. J. Rupnik M. Genheimer C. W. Sambol S. P. Lyerly D. M. (2006 ). Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J. Infect. Dis. 193 1143–1150.

    Not in our library10.1086/501368

  66. 66.
    Metabolism of Bile Salts in Mice Influences Spore Germination in Clostridium difficile · 2010
    No notice
  67. 67.

    Gil F. Lagos-Moraga S. Calderón-Romero P. Pizarro-Guajardo M. Paredes-Sabja D. (2017 ). Updates on Clostridium difficile spore biology. Anaerobe 45 3–9.

    Not in our library10.1016/j.anaerobe.2017.02.018

  68. 68.

    Guerrero D. M. Becker J. C. Eckstein E. C. Kundrapu S. Deshpande A. Sethi A. K. (2013 ). Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients. J. Hosp. Infect. 85 155–158.

    Not in our library10.1016/j.jhin.2013.07.002

  69. 69.

    Hafiz S. Oakley C. L. (1976 ). Clostridium difficile: isolation and characteristics. J. Med. Microbiol. 9 129–136.

    Not in our library10.1099/00222615-9-2-129

  70. 70.

    Hagel S. Epple H.-J. Feurle G. E. Kern W. V. Lynen Jansen P. Malfertheiner P. (2015 ). S2k-Leitlinie Gastrointestinale Infektionen und Morbus Whipple. Z. Gastroenterol. 53 418–459.

    Not in our library10.1055/s-0034-1399337

  71. 71.

    Hall I. C. and O′Toole E. (1935 ). Intestinal flora in new-born infants: with a description of a new pathogenic anaerobe, Bacillus difficilis. Am. J. Dis. Child. 2 390–402.

    Not in our library10.1001/archpedi.1935.01970020105010

  72. 72.

    Hamilton M. J. Weingarden A. R. Unno T. Khoruts A. Sadowsky M. J. (2013 ). High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes 4 125–135.

    Not in our library10.4161/gmic.23571

  73. 73.

    Hell M. Sickau K. Chmelizek G. Kern J. M. Maass M. Huhulescu S. (2012 ). Absence of Clostridium difficile in asymptomatic hospital staff. Am. J. Infect. Control 40 1023–1024.

    Not in our library10.1016/j.ajic.2012.01.018

  74. 74.
    Clinical Risk Factors for Severe Clostridium difficile –associated Disease · 2009
    No notice
  75. 75.

    Hopkins M. J. Sharp R. Macfarlane G. T. (2001 ). Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 48 198–205.

    Not in our library10.1136/gut.48.2.198

  76. 76.

    Howerton A. Ramirez N. Abel-Santos E. (2011 ). Mapping interactions between germinants and Clostridium difficile spores. J. Bacteriol. 193 274–282.

    Not in our library10.1128/jb.00980-10

  77. 77.

    Huurre A. Kalliomäki M. Rautava S. Rinne M. Salminen S. Isolauri E. (2008 ). Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology 93 236–240.

    Not in our library10.1159/000111102

  78. 78.

    Ishida Y. Maegawa T. Kondo T. Kimura A. Iwakura Y. Nakamura S. (2004 ). Essential involvement of IFN-gamma in Clostridium difficile toxin A-induced enteritis. J. Immunol. 172 3018–3025.

    Not in our library10.4049/jimmunol.172.5.3018

  79. 79.
    Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome · 2010
    No notice
  80. 80.

    Jangi S. Lamont J. T. (2010 ). Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. J. Pediatr. Gastroenterol. Nutr. 51 2–7.

    Not in our library10.1097/mpg.0b013e3181d29767

  81. 81.

    Jump R. L. P. Pultz M. J. Donskey C. J. (2007 ). Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea? Antimicrob. Agents Chemother. 51 2883–2887.

    Not in our library10.1128/aac.01443-06

  82. 82.

    Kallen A. J. Thompson A. Ristaino P. Chapman L. Nicholson A. Sim B.-T. (2009 ). Complete restriction of fluoroquinolone use to control an outbreak of Clostridium difficile infection at a community hospital. Infect. Control Hosp. Epidemiol. 30 264–272.

    Not in our library10.1086/595694

  83. 83.

    Kassam Z. Lee C. H. Yuan Y. Hunt R. H. (2013 ). Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am. J. Gastroenterol. 108 500–508.

    Not in our library10.1038/ajg.2013.59

  84. 84.

    Kato H. Kita H. Karasawa T. Maegawa T. Koino Y. Takakuwa H. (2001 ). Colonisation and transmission of Clostridium difficile in healthy individuals examined by PCR ribotyping and pulsed-field gel electrophoresis. J. Med. Microbiol. 50 720–727.

    Not in our library10.1099/0022-1317-50-8-720

  85. 85.

    Keel K. Brazier J. S. Post K. W. Weese S. Songer J. G. (2007 ). Prevalence of PCR ribotypes among Clostridium difficile isolates from pigs, calves, and other species. J. Clin. Microbiol. 45 1963–1964.

    Not in our library10.1128/jcm.00224-07

  86. 86.

    Kelly C. P. (1996 ). Immune response to Clostridium difficile infection. Eur. J. Gastroenterol. Hepatol. 8 1048–1053.

    Not in our library10.1097/00042737-199611000-00004

  87. 87.

    Kelly C. P. LaMont J. T. (1998 ). Clostridium difficile infection. Annu. Rev. Med. 49 375–390.

    Not in our library10.1146/annurev.med.49.1.375

  88. 88.

    Khanafer N. Vanhems P. Barbut F. Luxemburger C. (2017 ). Factors associated with Clostridium difficile infection: a nested case-control study in a three year prospective cohort. Anaerobe 44 117–123.

    Not in our library10.1016/j.anaerobe.2017.03.003

  89. 89.

    Khanna S. Baddour L. M. Huskins W. C. Kammer P. P. Faubion W. A. Zinsmeister A. R. (2013 ). The epidemiology of Clostridium difficile infection in children: a population-based study. Clin. Infect. Dis. 56 1401–1406.

    Not in our library10.1093/cid/cit075

  90. 90.

    Khanna S. Pardi D. S. Kelly C. R. Kraft C. S. Dhere T. Henn M. R. (2016 ). A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J. Infect. Dis. 214 173–181.

    Not in our library10.1093/infdis/jiv766

  91. 91.

    Kim J. H. Toy D. Muder R. R. (2011 ). Clostridium difficile infection in a long-term care facility: hospital-associated illness compared with long-term care-associated illness. Infect. Control Hosp. Epidemiol. 32 656–660.

    Not in our library10.1086/660767

  92. 92.

    Kobayashi T. (1983 ). Studies on Clostridium difficile and antimicrobial associated diarrhea or colitis. Jpn. J. Antibiot. 36 464–476.

    Not in our library

  93. 93.

    Komatsu M. Kato H. Aihara M. Shimakawa K. Iwasaki M. Nagasaka Y. (2003 ). High frequency of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive Clostridium difficile in a hospital in Japan and risk factors for infection. Eur. J. Clin. Microbiol. Infect. Dis. 22 525–529.

    Not in our library10.1007/s10096-003-0992-5

  94. 94.

    Kong L. Y. Dendukuri N. Schiller I. Bourgault A.-M. Brassard P. Poirier L. (2015 ). Predictors of asymptomatic Clostridium difficile colonization on hospital admission. Am. J. Infect. Control 43 248–253.

    Not in our library10.1016/j.ajic.2014.11.024

  95. 95.

    Kuijper E. J. Coignard B. Tüll P. (2006 ). Emergence of Clostridium difficile-associated disease in North America and Europe. Clin. Microbiol. Infect. 12(Suppl. 6), 2–18.

    Not in our library10.1111/j.1469-0691.2006.01580.x

  96. 96.

    Kyne L. Warny M. Qamar A. Kelly C. P. (2000 ). Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N. Engl. J. Med. 342 390–397.

    Not in our library10.1056/nejm200002103420604

  97. 97.

    Kyne L. Warny M. Qamar A. Kelly C. P. (2001 ). Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357 189–193.

    Not in our library10.1016/s0140-6736(00)03592-3

  98. 98.

    Larson H. E. Barclay F. E. Honour P. Hill I. D. (1982 ). Epidemiology of Clostridium difficile in infants. J. Infect. Dis. 146 727–733.

    Not in our library10.1093/infdis/146.6.727

  99. 99.
    Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice · 2012
    No notice
  100. 100.

    Leekha S. Aronhalt K. C. Sloan L. M. Patel R. Orenstein R. (2013 ). Asymptomatic Clostridium difficile colonization in a tertiary care hospital: admission prevalence and risk factors. Am. J. Infect. Control 41 390–393.

    Not in our library10.1016/j.ajic.2012.09.023

  101. 101.

    Lessa F. C. Winston L. G. McDonald L. C. (2015 ). Burden of Clostridium difficile infection in the United States. N. Engl. J. Med. 372 2369–2370.

    Not in our library10.1056/nejmc1505190

  102. 102.

    Ley R. E. Peterson D. A. Gordon J. I. (2006 ). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124 837–848.

    Not in our library10.1016/j.cell.2006.02.017

  103. 103.

    Lo Vecchio A. Zacur G. M. (2012 ). Clostridium difficile infection: an update on epidemiology, risk factors, and therapeutic options. Curr. Opin. Gastroenterol. 28 1–9.

    Not in our library10.1097/mog.0b013e32834bc9a9

  104. 104.

    Longtin Y. Paquet-Bolduc B. Gilca R. Garenc C. Fortin E. Longtin J. (2016 ). Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C. difficile infections: a quasi-experimental controlled study. JAMA Intern. Med. 176 796–804.

    Not in our library10.1001/jamainternmed.2016.0177

  105. 105.

    Loo V. G. Bourgault A.-M. Poirier L. Lamothe F. Michaud S. Turgeon N. (2011 ). Host and pathogen factors for Clostridium difficile infection and colonization. N. Engl. J. Med. 365 1693–1703.

    Not in our library10.1056/nejmoa1012413

  106. 106.

    Loo V. G. Poirier L. Miller M. A. Oughton M. Libman M. D. Michaud S. (2005 ). A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N. Engl. J. Med. 353 2442–2449.

    Not in our library10.1056/nejmoa051639

  107. 107.

    Louie T. J. Miller M. A. Mullane K. M. Weiss K. Lentnek A. Golan Y. (2011 ). Fidaxomicin versus vancomycin for Clostridium difficile infection. N. Engl. J. Med. 364 422–431.

    Not in our library10.1056/nejmoa0910812

  108. 108.

    Lyerly D. M. Saum K. E. MacDonald D. K. Wilkins T. D. (1985 ). Effects of Clostridium difficile toxins given intragastrically to animals. Infect. Immun. 47 349–352.

    Not in our library10.1128/iai.47.2.349-352.1985

  109. 109.

    Lyras D. O’Connor J. R. Howarth P. M. Sambol S. P. Carter G. P. Phumoonna T. (2009 ). Toxin B is essential for virulence of Clostridium difficile. Nature 458 1176–1179.

    Not in our library10.1038/nature07822

  110. 110.

    Manges A. R. Labbe A. Loo V. G. Atherton J. K. Behr M. A. Masson L. (2010 ). Comparative metagenomic study of alterations to the intestinal microbiota and risk of nosocomial Clostridium difficile-associated disease. J. Infect. Dis. 202 1877–1884.

    Not in our library10.1086/657319

  111. 111.

    Marciniak C. Chen D. Stein A. C. Semik P. E. (2006 ). Prevalence of Clostridium difficile colonization at admission to rehabilitation. Arch. Phys. Med. Rehabil. 87 1086–1090.

    Not in our library10.1016/j.apmr.2006.03.020

  112. 112.
    The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age · 2009
    No notice
  113. 113.

    Matamoros S. Gras-Leguen C. Le Vacon F. Potel G. de La Cochetiere M.-F. (2013 ). Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 21 167–173.

    Not in our library10.1016/j.tim.2012.12.001

  114. 114.

    Maziade P.-J. Pereira P. Goldstein E. J. C. (2015 ). A decade of experience in primary prevention of Clostridium difficile infection at a community hospital using the probiotic combination Lactobacillus acidophilus CL1285 Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+). Clin. Infect. Dis. 60(Suppl. 2), S144–S147.

    Not in our library10.1093/cid/civ178

  115. 115.
    Fluoroquinolone Use and Clostridium difficile –associated Diarrhea · 2003
    No notice
  116. 116.
    Clostridium difficile Infection in Patients Discharged from US Short-stay Hospitals, 1996–20031 · 2006
    No notice
  117. 117.

    McFarland L. V. Beneda H. W. Clarridge J. E. Raugi G. J. (2007a ). Implications of the changing face of Clostridium difficile disease for health care practitioners. Am. J. Infect. Control 35 237–253.

    Not in our library10.1016/j.ajic.2006.06.004

  118. 118.

    McFarland L. V. Clarridge J. E. Beneda H. W. Raugi G. J. (2007b ). Fluoroquinolone use and risk factors for Clostridium difficile-associated disease within a Veterans Administration health care system. Clin. Infect. Dis. 45 1141–1151.

    Not in our library10.1086/522187

  119. 119.

    McFarland L. V. Elmer G. W. Stamm W. E. Mulligan M. E. (1991 ). Correlation of immunoblot type, enterotoxin production, and cytotoxin production with clinical manifestations of Clostridium difficile infection in a cohort of hospitalized patients. Infect. Immun. 59 2456–2462.

    Not in our library10.1128/iai.59.7.2456-2462.1991

  120. 120.

    McFarland L. V. Mulligan M. E. Kwok R. Y. Stamm W. E. (1989 ). Nosocomial acquisition of Clostridium difficile infection. N. Engl. J. Med. 320 204–210.

    Not in our library10.1056/nejm198901263200402

  121. 121.

    McFarland L. V. Ozen M. Dinleyici E. C. Goh S. (2016 ). Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. World J. Gastroenterol. 22 3078–3104.

    Not in our library10.3748/wjg.v22.i11.3078

  122. 122.

    Merrigan M. M. Sambol S. P. Johnson S. Gerding D. N. (2003 ). Prevention of fatal Clostridium difficile-associated disease during continuous administration of clindamycin in hamsters. J. Infect. Dis. 188 1922–1927.

    Not in our library10.1086/379836

  123. 123.

    Merrigan M. M. Sambol S. P. Johnson S. Gerding D. N. (2009 ). New approach to the management of Clostridium difficile infection: colonisation with non-toxigenic C. difficile during daily ampicillin or ceftriaxone administration. Int. J. Antimicrob. Agents 33(Suppl. 1), S46–S50.

    Not in our library10.1016/s0924-8579(09)70017-2

  124. 124.

    Meyer G. K. A. Neetz A. Brandes G. Tsikas D. Butterfield J. H. Just I. (2007 ). Clostridium difficile toxins A and B directly stimulate human mast cells. Infect. Immun. 75 3868–3876.

    Not in our library10.1128/iai.00195-07

  125. 125.

    Miller M. Gravel D. Mulvey M. Taylor G. Boyd D. Simor A. (2010 ). Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin. Infect. Dis. 50 194–201.

    Not in our library10.1086/649213

  126. 126.

    Moore P. Kyne L. Martin A. Solomon K. (2013 ). Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure. J. Med. Microbiol. 62 1405–1413.

    Not in our library10.1099/jmm.0.056614-0

  127. 127.

    Morris J. G. Jarvis W. R. Nunez-Montiel O. L. Towns M. L. Thompson F. S. Dowell V. R. (1984 ). Clostridium difficile. Colonization and toxin production in a cohort of patients with malignant hematologic disorders. Arch. Intern. Med. 144 967–969.

    Not in our library10.1001/archinte.1984.00350170109020

  128. 128.

    Muegge B. D. Kuczynski J. Knights D. Clemente J. C. González A. Fontana L. (2011 ). Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332 970–974.

    Not in our library10.1126/science.1198719

  129. 129.

    Muto C. A. Pokrywka M. Shutt K. Mendelsohn A. B. Nouri K. Posey K. (2005 ). A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect. Control Hosp. Epidemiol. 26 273–280.

    Not in our library10.1086/502539

  130. 130.

    Naaber P. Lehto E. Salminen S. Mikelsaar M. (1996 ). Inhibition of adhesion of Clostridium difficile to Caco-2 cells. FEMS Immunol. Med. Microbiol. 14 205–209.

    Not in our library10.1111/j.1574-695x.1996.tb00288.x

  131. 131.

    Nakamura S. Mikawa M. Nakashio S. Takabatake M. Okado I. Yamakawa K. (1981 ). Isolation of Clostridium difficile from the feces and the antibody in sera of young and elderly adults. Microbiol. Immunol. 25 345–351.

    Not in our library10.1111/j.1348-0421.1981.tb00036.x

  132. 132.

    Nelson D. E. Auerbach S. B. Baltch A. L. Desjardin E. Beck-Sague C. Rheal C. (1994 ). Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins. Infect. Control Hosp. Epidemiol. 15 88–94.

    Not in our library10.2307/30145537

  133. 133.
    Acid suppression therapy does not predispose to Clostridium difficile infection: the case of the potential bias. · 2014
    Not checked
  134. 134.

    Nylund C. M. Goudie A. Garza J. M. Fairbrother G. Cohen M. B. (2011 ). Clostridium difficile infection in hospitalized children in the United States. Arch. Pediatr. Adolesc. Med. 165 451–457.

    Not in our library10.1001/archpediatrics.2010.282

  135. 135.

    Ogra P. L. (2010 ). Ageing and its possible impact on mucosal immune responses. Ageing Res. Rev. 9 101–106.

    Not in our library10.1016/j.arr.2009.07.007

  136. 136.

    Ozaki E. Kato H. Kita H. Karasawa T. Maegawa T. Koino Y. (2004 ). Clostridium difficile colonization in healthy adults: transient colonization and correlation with enterococcal colonization. J. Med. Microbiol. 53 167–172.

    Not in our library10.1099/jmm.0.05376-0

  137. 137.

    Pakpour S. Bhanvadia A. Zhu R. Amarnani A. Gibbons S. M. Gurry T. (2017 ). Identifying predictive features of Clostridium difficile infection recurrence before, during, and after primary antibiotic treatment. Microbiome 5:148.

    Not in our library10.1186/s40168-017-0368-1

  138. 138.

    Peach S. L. Borriello S. P. Gaya H. Barclay F. E. Welch A. R. (1986 ). Asymptomatic carriage of Clostridium difficile in patients with cystic fibrosis. J. Clin. Pathol. 39 1013–1018.

    Not in our library10.1136/jcp.39.9.1013

  139. 139.

    Pépin J. Valiquette L. Cossette B. (2005 ). Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 173 1037–1042.

    Not in our library10.1503/cmaj.050978

  140. 140.
    Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile. · 2012
    Not checked
  141. 141.

    Pirs T. Ocepek M. Rupnik M. (2008 ). Isolation of Clostridium difficile from food animals in Slovenia. J. Med. Microbiol. 57 790–792.

    Not in our library10.1099/jmm.0.47669-0

  142. 142.

    Pochapin M. (2000 ). The effect of probiotics on Clostridium difficile diarrhea. Am. J. Gastroenterol. 95 S11–S13.

    Not in our library10.1016/s0002-9270(99)00809-6

  143. 143.

    Pruitt R. N. Lacy D. B. (2012 ). Toward a structural understanding of Clostridium difficile toxins A and B. Front. Cell. Infect. Microbiol. 2:28.

    Not in our library10.3389/fcimb.2012.00028

  144. 144.
    Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults · 2009
    No notice
  145. 145.

    Rea M. C. Clayton E. O’Connor P. M. Shanahan F. Kiely B. Ross R. P. (2007 ). Antimicrobial activity of lacticin 3147 against clinical Clostridium difficile strains. J. Med. Microbiol. 56 940–946.

    Not in our library10.1099/jmm.0.47085-0

  146. 146.

    Rea M. C. O’Sullivan O. Shanahan F. O’Toole P. W. Stanton C. Ross R. P. (2012 ). Clostridium difficile carriage in elderly subjects and associated changes in the intestinal microbiota. J. Clin. Microbiol. 50 867–875.

    Not in our library10.1128/jcm.05176-11

  147. 147.

    Reeves A. E. Koenigsknecht M. J. Bergin I. L. Young V. B. (2012 ). Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect. Immun. 80 3786–3794.

    Not in our library10.1128/iai.00647-12

  148. 148.

    Reeves A. E. Theriot C. M. Bergin I. L. Huffnagle G. B. Schloss P. D. Young V. B. (2011 ). The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile infection. Gut Microbes 2 145–158.

    Not in our library10.4161/gmic.2.3.16333

  149. 149.

    Reichardt C. Chaberny I. F. Kola A. Mattner F. Vonberg R. P. Gastmeier P. (2007 ). Dramatischer Anstieg von Clostridium-difficile-assoziierter Diarrhoe in Deutschland: Ist der neue Stamm PCR-Ribotyp 027 bereits angekommen? Dtsch. Med. Wochenschr. 132 223–228.

    Not in our library10.1055/s-2007-959314

  150. 150.

    Richardson S. A. Alcock P. A. Gray J. (1983 ). Clostridium difficile and its toxin in healthy neonates. Br. Med. J. (Clin. Res. Ed) 287:878.

    Not in our library10.1136/bmj.287.6396.878

  151. 151.

    Riggs M. M. Sethi A. K. Zabarsky T. F. Eckstein E. C. Jump R. L. P. Donskey C. J. (2007 ). Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin. Infect. Dis. 45 992–998.

    Not in our library10.1086/521854

  152. 152.

    Ringel Y. Maharshak N. (2013 ). Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome. Am. J. Physiol. Gastrointest. Liver Physiol. 305 G529–G541.

    Not in our library10.1152/ajpgi.00207.2012

  153. 153.

    Robinson C. J. Young V. B. (2010 ). Antibiotic administration alters the community structure of the gastrointestinal micobiota. Gut Microbes 1 279–284.

    Not in our library10.4161/gmic.1.4.12614

  154. 154.

    Rodriguez-Palacios A. Reid-Smith R. J. Staempfli H. R. Daignault D. Janecko N. Avery B. P. (2009 ). Possible seasonality of Clostridium difficile in retail meat, Canada. Emerg. Infect. Dis. 15 802–805.

    Not in our library10.3201/eid1505.081084

  155. 155.
    Clostridium difficile in Retail Ground Meat, Canada · 2007
    No notice
  156. 156.

    Rolfe R. D. Song W. (1995 ). Immunoglobulin and non-immunoglobulin components of human milk inhibit Clostridium difficile toxin A-receptor binding. J. Med. Microbiol. 42 10–19.

    Not in our library10.1099/00222615-42-1-10

  157. 157.

    Rousseau C. Poilane I. Pontual L. de Maherault A.-C. Le Monnier A. Collignon A. (2012 ). Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin. Infect. Dis. 55 1209–1215.

    Not in our library10.1093/cid/cis637

  158. 158.

    Rupnik M. Wilcox M. H. Gerding D. N. (2009 ). Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7 526–536.

    Not in our library10.1038/nrmicro2164

  159. 159.

    Sambol S. P. Merrigan M. M. Tang J. K. Johnson S. Gerding D. N. (2002 ). Colonization for the prevention of Clostridium difficile disease in hamsters. J. Infect. Dis. 186 1781–1789.

    Not in our library10.1086/345676

  160. 160.

    Samore M. H. DeGirolami P. C. Tlucko A. Lichtenberg D. A. Melvin Z. A. Karchmer A. W. (1994 ). Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin. Infect. Dis. 18 181–187.

    Not in our library10.1093/clinids/18.2.181

  161. 161.

    Sarker M. R. Paredes-Sabja D. (2012 ). Molecular basis of early stages of Clostridium difficile infection: germination and colonization. Future Microbiol. 7 933–943.

    Not in our library10.2217/fmb.12.64

  162. 162.

    Schirmer J. Aktories K. (2004 ). Large clostridial cytotoxins: cellular biology of Rho/Ras-glucosylating toxins. Biochim. Biophys. Acta 1673 66–74.

    Not in our library10.1016/j.bbagen.2004.03.014

  163. 163.

    Schultsz C. van den Berg F. M. Kate F. W. ten Tytgat G. N. Dankert J. (1999 ). The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology 117 1089–1097.

    Not in our library10.1016/s0016-5085(99)70393-8

  164. 164.

    Schwartz K. L. Darwish I. Richardson S. E. Mulvey M. R. Thampi N. (2014 ). Severe clinical outcome is uncommon in Clostridium difficile infection in children: a retrospective cohort study. BMC Pediatr. 14:28.

    Not in our library10.1186/1471-2431-14-28

  165. 165.

    Sekirov I. Russell S. L. Antunes L. C. M. Finlay B. B. (2010 ). Gut microbiota in health and disease. Physiol. Rev. 90 859–904.

    Not in our library10.1152/physrev.00045.2009

  166. 166.

    Shen A. (2012 ). Clostridium difficile toxins: mediators of inflammation. J. Innate Immun. 4 149–158.

    Not in our library10.1159/000332946

  167. 167.

    Shen N. T. Maw A. Tmanova L. L. Pino A. Ancy K. Crawford C. V. (2017 ). Timely use of probiotics in hospitalized adults prevents Clostridium difficile infection: a systematic review with meta-regression analysis. Gastroenterology 152 1889.e9–1900.e9.

    Not in our library10.1053/j.gastro.2017.02.003

  168. 168.

    Shim J. K. Johnson S. Samore M. H. Bliss D. Z. Gerding D. N. (1998 ). Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 351 633–636.

    Not in our library10.1016/s0140-6736(97)08062-8

  169. 169.

    Simor A. E. Bradley S. F. Strausbaugh L. J. Crossley K. Nicolle L. E. (2002 ). Clostridium difficile in long-term-care facilities for the elderly. Infect. Control Hosp. Epidemiol. 23 696–703.

    Not in our library10.1086/501997

  170. 170.

    Songer J. G. Jones R. Anderson M. A. Barbara A. J. Post K. W. Trinh H. T. (2007 ). Prevention of porcine Clostridium difficile-associated disease by competitive exclusion with nontoxigenic organisms. Vet. Microbiol. 124 358–361.

    Not in our library10.1016/j.vetmic.2007.04.019

  171. 171.

    Sorg J. A. Sonenshein A. L. (2008 ). Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190 2505–2512.

    Not in our library10.1128/jb.01765-07

  172. 172.

    Spigaglia P. (2016 ). Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection. Ther. Adv. Infect. Dis. 3 23–42.

    Not in our library10.1177/2049936115622891

  173. 173.

    Stark P. L. Lee A. (1982 ). Clostridia isolated from the feces of infants during the first year of life. J. Pediatr. 100 362–365.

    Not in our library10.1016/s0022-3476(82)80430-7

  174. 174.

    Steele J. Mukherjee J. Parry N. Tzipori S. (2013 ). Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease. J. Infect. Dis. 207 323–330.

    Not in our library10.1093/infdis/jis669

  175. 175.

    Stevens V. Dumyati G. Fine L. S. Fisher S. G. van Wijngaarden E. (2011 ). Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin. Infect. Dis. 53 42–48.

    Not in our library10.1093/cid/cir301

  176. 176.

    Sullivan A. Edlund C. Nord C. E. (2001 ). Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect. Dis. 1 101–114.

    Not in our library10.1016/s1473-3099(01)00066-4

  177. 177.

    Tattevin P. Buffet-Bataillon S. Donnio P.-Y. Revest M. Michelet C. (2013 ). Clostridium difficile infections: do we know the real dimensions of the problem? Int. J. Antimicrob. Agents 42(Suppl.) S36–S40.

    Not in our library10.1016/j.ijantimicag.2013.04.009

  178. 178.

    Tedesco F. J. Barton R. W. Alpers D. H. (1974 ). Clindamycin-associated colitis. A prospective study. Ann. Intern. Med. 81 429–433.

    Not in our library10.7326/0003-4819-81-4-429

  179. 179.

    Terveer E. M. Crobach M. J. T. Sanders I. M. J. G. Vos M. C. Verduin C. M. Kuijper E. J. (2017 ). Detection of Clostridium difficile in feces of asymptomatic patients admitted to the hospital. J. Clin. Microbiol. 55 403–411.

    Not in our library10.1128/jcm.01858-16

  180. 180.

    Theriot C. M. Koenigsknecht M. J. Carlson P. E. Hatton G. E. Nelson A. M. Li B. (2014 ). Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5:3114.

    Not in our library10.1038/ncomms4114

  181. 181.

    Thompson C. M. Gilligan P. H. Fisher M. C. Long S. S. (1983 ). Clostridium difficile cytotoxin in a pediatric population. Am. J. Dis. Child. 137 271–274.

    Not in our library10.1001/archpedi.1983.02140290057015

  182. 182.

    Trzasko A. Leeds J. A. Praestgaard J. Lamarche M. J. McKenney D. (2012 ). Efficacy of LFF571 in a hamster model of Clostridium difficile infection. Antimicrob. Agents Chemother. 56 4459–4462.

    Not in our library10.1128/aac.06355-11

  183. 183.

    van Dorp S. M. Smajlovic E. Knetsch C. W. Notermans D. W. de Greeff S. C. Kuijper E. J. (2017 ). Clinical and microbiological characteristics of Clostridium difficile infection among hospitalized children in the Netherlands. Clin. Infect. Dis. 64 192–198.

    Not in our library10.1093/cid/ciw699

  184. 184.

    van Nood E. Vrieze A. Nieuwdorp M. Fuentes S. Zoetendal E. G. de Vos W. M. (2013 ). Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368 407–415.

    Not in our library10.1056/nejmoa1205037

  185. 185.

    Vardakas K. Z. Polyzos K. A. Patouni K. Rafailidis P. I. Samonis G. Falagas M. E. (2012 ). Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence. Int. J. Antimicrob. Agents 40 1–8.

    Not in our library10.1016/j.ijantimicag.2012.01.004

  186. 186.

    Vernaya M. McAdam J. Hampton M. D. (2017 ). Effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients: a systematic review. JBI Database System. Rev. Implement. Rep. 15 140–164.

    Not in our library10.11124/jbisrir-2016-003234

  187. 187.

    Vincent C. Miller M. A. Edens T. J. Mehrotra S. Dewar K. Manges A. R. (2016 ). Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection. Microbiome 4:12.

    Not in our library10.1186/s40168-016-0156-3

  188. 188.

    Vincent C. Stephens D. A. Loo V. G. Edens T. J. Behr M. A. Dewar K. (2013 ). Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiome 1:18.

    Not in our library10.1186/2049-2618-1-18

  189. 189.

    Viscidi R. Willey S. Bartlett J. G. (1981 ). Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 81 5–9.

    Not in our library

  190. 190.

    Voth D. E. Ballard J. D. (2005 ). Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18 247–263.

    Not in our library10.1128/cmr.18.2.247-263.2005

  191. 191.

    Warny M. Pepin J. Fang A. Killgore G. Thompson A. Brazier J. (2005 ). Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366 1079–1084.

    Not in our library10.1016/s0140-6736(05)67420-x

  192. 192.

    Weese J. S. (2010 ). Clostridium difficile in food–innocent bystander or serious threat? Clin. Microbiol. Infect. 16 3–10.

    Not in our library10.1111/j.1469-0691.2009.03108.x

  193. 193.

    Welkon C. J. Long S. S. Thompson C. M. Gilligan P. H. (1985 ). Clostridium difficile in patients with cystic fibrosis. Am. J. Dis. Child. 139 805–808.

    Not in our library10.1001/archpedi.1985.02140100067032

  194. 194.

    Werner H. Kuntsche J. (2000 ). Infektionen im Alter–was ist anders? Z. Gerontol. Geriatr. 33 350–356.

    Not in our library10.1007/s003910070031

  195. 195.

    Wilcox M. H. Gerding D. N. Poxton I. R. Kelly C. Nathan R. Birch T. (2017 ). Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N. Engl. J. Med. 376 305–317.

    Not in our library10.1056/nejmoa1602615

  196. 196.

    Wilson K. H. (1983 ). Efficiency of various bile salt preparations for stimulation of Clostridium difficile spore germination. J. Clin. Microbiol. 18 1017–1019.

    Not in our library10.1128/jcm.18.4.1017-1019.1983

  197. 197.

    Wilson K. H. Perini F. (1988 ). Role of competition for nutrients in suppression of Clostridium difficile by the colonic microflora. Infect. Immun. 56 2610–2614.

    Not in our library10.1128/iai.56.10.2610-2614.1988

  198. 198.

    Wilson K. H. Silva J. Fekety F. R. (1981 ). Suppression of Clostridium difficile by normal hamster cecal flora and prevention of antibiotic-associated cecitis. Infect. Immun. 34 626–628.

    Not in our library10.1128/iai.34.2.626-628.1981

  199. 199.

    Winston J. A. Thanissery R. Montgomery S. A. Theriot C. M. (2016 ). Cefoperazone-treated mouse model of clinically-relevant Clostridium difficile strain R20291. J. Vis. Exp. 118:e54850.

    Not in our library10.3791/54850

  200. 200.

    Wongwanich S. Pongpech P. Dhiraputra C. Huttayananont S. Sawanpanyalert P. (2001 ). Characteristics of Clostridium difficile strains isolated from asymptomatic individuals and from diarrheal patients. Clin. Microbiol. Infect. 7 438–441.

    Not in our library10.1046/j.1198-743x.2001.00308.x

  201. 201.

    Woodmansey E. J. (2007 ). Intestinal bacteria and ageing. J. Appl. Microbiol. 102 1178–1186.

    Not in our library10.1111/j.1365-2672.2007.03400.x

  202. 202.

    Wu G. D. Chen J. Hoffmann C. Bittinger K. Chen Y.-Y. Keilbaugh S. A. (2011 ). Linking long-term dietary patterns with gut microbial enterotypes. Science 334 105–108.

    Not in our library10.1126/science.1208344

  203. 203.

    Wullt M. Hagslätt M.-L. J. Odenholt I. (2003 ). Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scand. J. Infect. Dis. 35 365–367.

    Not in our library10.1080/00365540310010985

  204. 204.

    Yaeger M. J. Kinyon J. M. Glenn Songer J. (2007 ). A prospective, case control study evaluating the association between Clostridium difficile toxins in the colon of neonatal swine and gross and microscopic lesions. J. Vet. Diagn. Invest. 19 52–59.

    Not in our library10.1177/104063870701900108

  205. 205.

    Yatsunenko T. Rey F. E. Manary M. J. Trehan I. Dominguez-Bello M. G. Contreras M. (2012 ). Human gut microbiome viewed across age and geography. Nature 486 222–227.

    Not in our library10.1038/nature11053

  206. 206.

    Zacharioudakis I. M. Zervou F. N. Pliakos E. E. Ziakas P. D. Mylonakis E. (2015 ). Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am. J. Gastroenterol. 110 381–390; quiz 391.

    Not in our library10.1038/ajg.2015.22

  207. 207.

    Zilberberg M. D. Shorr A. F. Kollef M. H. (2008 ). Increase in Clostridium difficile-related hospitalizations among infants in the United States, 2000-2005. Pediatr. Infect. Dis. J. 27 1111–1113.

    Not in our library10.1097/inf.0b013e31817eef13

  208. 208.
    Analysis of the Gut Microbiota in the Old Order Amish and Its Relation to the Metabolic Syndrome · 2012
    No notice

Cited by papers we hold 4

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.