Using Spatial and Temporal Mapping to Identify Nosocomial Disease Transmission of Clostridium difficile

Abstract Background Clostridium difficile is a major cause of healthcare-associated infections leading to significant morbidity and mortality; however, data-driven interventions to decrease C. difficile infections (CDI) are lacking due to an incomplete understanding of disease transmission and risk factors. Asymptomatic C. difficile carriers may be an important source of nosocomial transmission and disease but few studies have examined colonized patients who later develop CDI. We describe risk factors for the development of CDI in a critical care population screened for C. difficile colonization. Methods All patients admitted to our medical or trauma ICUs were screened for toxigenic C. difficile by PCR via rectal swab. Colonized patients were placed in contact enteric precautions for their entire hospitalization and monitored for signs and symptoms of CDI. Retrospective chart review assessed risk factors associated with development of CDI. Results 868 rectal swabs were collected from 4/01/16 to 10/31/16. 40 patients were colonized with C. difficile on ICU admission and 20 developed symptomatic CDI (Table 1). Risk factors for CDI in colonized patients include enteral feeding and exposure to antibiotics (Table 2). Conclusion 50% of C. difficile colonized ICU patients progressed to symptomatic CDI during their hospitalization. Antibiotic use was a significant risk factor for CDI. C. difficile carriers may be a particularly vulnerable population for CDI, warranting further investigation for early identification of colonized patients and strategies for infection prevention. Disclosures F. C. Fang, BioFire: Collaborator, Consultant and Scientific Advisor, Consulting fee, Research support and Speaker honorarium; Cepheid: Collaborator, Consultant and Scientific Advisor, Consulting fee, Educational grant, Research support and Speaker honorarium

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Role of the hospital environment in disease transmission, with a focus on Clostridium difficile

Healthcare Infection ◽

10.1071/hi12057 ◽

2013 ◽

Vol 18 (1) ◽

pp. 14-22 ◽

Cited By ~ 9

Author(s):

William A. Rutala ◽

David J. Weber

Keyword(s):

Clostridium Difficile ◽

Disease Transmission ◽

Hospital Environment

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Isolation of Environmental Clostridium Difficile from a Veterinary Teaching Hospital

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870001200510 ◽

2000 ◽

Vol 12 (5) ◽

pp. 449-452 ◽

Cited By ~ 40

Author(s):

J. Scott Weese ◽

Henri R. Staempfli ◽

John F. Prescott

Keyword(s):

Clostridium Difficile ◽

Teaching Hospital ◽

Potential Role ◽

Sodium Taurocholate ◽

Fecal Contamination ◽

Small Animal ◽

Large Animal ◽

High Animal ◽

Nosocomial Disease

An environmental survey of a veterinary teaching hospital for the presence of Clostridium difficile was performed using contact plates and cycloserine-cefoxitin-fructose with 0.1% sodium taurocholate agar. Clostridium difficile was isolated from 24 of 381 sites (6.3%). Growth was obtained from 4.5% (9/202) of sites sampled in the Large Animal Clinic, from 8.1% (13/160) of sites within the Small Animal Clinic, and from 20% (2/10) of sites sampled elsewhere. Fourteen of 21 strains tested produced toxins in vitro. A geographic association was found with areas in the large animal clinic where nosocomial C. difficile diarrhea in horses had previously been diagnosed. Several other sites with a potential for nosocomial transmission of the organism were identified. Areas from which C. difficile was isolated tended to be areas with high animal traffic, with increased chance of fecal contamination, and with rough, difficult to clean surfaces. This study documents the prevalence of this organism in the environment and its potential role in nosocomial disease.

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Disease transmission model for community-associated Clostridium difficile infection

Epidemiology and Infection ◽

10.1017/s0950268809991646 ◽

2010 ◽

Vol 138 (6) ◽

pp. 907-914 ◽

Cited By ~ 31

Author(s):

A. M. OTTEN ◽

R. J. REID-SMITH ◽

A. FAZIL ◽

J. S. WEESE

Keyword(s):

Risk Factors ◽

Risk Assessment ◽

Clostridium Difficile ◽

Disease Transmission ◽

Initial Step ◽

Quantitative Risk Assessment ◽

Transmission Model ◽

Research Areas ◽

Canadian Workshop ◽

Disease Transmission Model

SUMMARYParticipating researchers and public health personnel at a Canadian workshop in 2007, noted considerable gaps in current understanding of community-associated Clostridium difficile infection (CA-CDI), specifically infection sources and risk factors. A disease transmission model for CA-CDI was requested as an initial step towards a risk assessment, to analyse infection sources and risk factors, addressing priority research areas. The developed model contains eight infection states (susceptible, gastrointestinal exposure, colonized, diseased, deceased, clinically resolved colonized, relapse diseased, and cleared) and notes directional transfers between the states. Most published research used focused on hospital-associated C. difficile infection (HA-CDI) and further studies are needed to substantiate the use of HA-CDI knowledge in the transmission of CA-CDI. The aim was to provide a consistent framework for researchers, and provide a theoretical basis for future quantitative risk assessment of CA-CDI.

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Proteomic and Genomic Characterization of Highly Infectious Clostridium difficile 630 Spores

Journal of Bacteriology ◽

10.1128/jb.00597-09 ◽

2009 ◽

Vol 191 (17) ◽

pp. 5377-5386 ◽

Cited By ~ 159

Author(s):

Trevor D. Lawley ◽

Nicholas J. Croucher ◽

Lu Yu ◽

Simon Clare ◽

Mohammed Sebaihia ◽

...

Keyword(s):

Clostridium Difficile ◽

Disease Transmission ◽

Significant Proportion ◽

Protein Stabilization ◽

Spectrometric Analysis ◽

Host Interactions ◽

Hospital Environments ◽

Genomic Characterization ◽

Clostridial Species ◽

Definition Of

ABSTRACT Clostridium difficile, a major cause of antibiotic-associated diarrhea, produces highly resistant spores that contaminate hospital environments and facilitate efficient disease transmission. We purified C. difficile spores using a novel method and show that they exhibit significant resistance to harsh physical or chemical treatments and are also highly infectious, with <7 environmental spores per cm2 reproducibly establishing a persistent infection in exposed mice. Mass spectrometric analysis identified ∼336 spore-associated polypeptides, with a significant proportion linked to translation, sporulation/germination, and protein stabilization/degradation. In addition, proteins from several distinct metabolic pathways associated with energy production were identified. Comparison of the C. difficile spore proteome to those of other clostridial species defined 88 proteins as the clostridial spore “core” and 29 proteins as C. difficile spore specific, including proteins that could contribute to spore-host interactions. Thus, our results provide the first molecular definition of C. difficile spores, opening up new opportunities for the development of diagnostic and therapeutic approaches.

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SleC Is Essential for Germination of Clostridium difficile Spores in Nutrient-Rich Medium Supplemented with the Bile Salt Taurocholate

Journal of Bacteriology ◽

10.1128/jb.01209-09 ◽

2009 ◽

Vol 192 (3) ◽

pp. 657-664 ◽

Cited By ~ 80

Author(s):

David A. Burns ◽

John T. Heap ◽

Nigel P. Minton

Keyword(s):

Health Care ◽

Bacillus Subtilis ◽

Clostridium Difficile ◽

Disease Transmission ◽

Health Care Services ◽

Lytic Enzyme ◽

Rich Medium ◽

Infectious Diarrhea ◽

Care Services ◽

Nutrient Rich Medium

ABSTRACT Clostridium difficile is the major cause of infectious diarrhea and a major burden to health care services. The ability of this organism to form endospores plays a pivotal role in infection and disease transmission. Spores are highly resistant to many forms of disinfection and thus are able to persist on hospital surfaces and disseminate infection. In order to cause disease, the spores must germinate and the organism must grow vegetatively. Spore germination in Bacillus is well understood, and genes important for this process have recently been identified in Clostridium perfringens; however, little is known about C. difficile. Apparent homologues of the spore cortex lytic enzyme genes cwlJ and sleB (Bacillus subtilis) and sleC (C. perfringens) are present in the C. difficile genome, and we describe inactivation of these homologues in C. difficile 630Δerm and a B1/NAP1/027 clinical isolate. Spores of a sleC mutant were unable to form colonies when germination was induced with taurocholate, although decoated sleC spores formed the same number of heat-resistant colonies as the parental control, even in the absence of germinants. This suggests that sleC is absolutely required for conversion of spores to vegetative cells, in contrast to CD3563 (a cwlJ/sleB homologue), inactivation of which had no effect on germination and outgrowth of C. difficile spores under the same conditions. The B1/NAP1/027 strain R20291 was found to sporulate more slowly and produce fewer spores than 630Δerm. Furthermore, fewer R20291 spores germinated, indicating that there are differences in both sporulation and germination between these epidemic and nonepidemic C. difficile isolates.

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Crystal structures of the GH18 domain of the bifunctional peroxiredoxin–chitinase CotE from Clostridium difficile

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x20006147 ◽

2020 ◽

Vol 76 (6) ◽

pp. 241-249

Author(s):

Jean L. Whittingham ◽

Shumpei Hanai ◽

James A. Brannigan ◽

William T. Ferreira ◽

Eleanor J. Dodson ◽

...

Keyword(s):

Clostridium Difficile ◽

Disease Transmission ◽

Anaerobic Bacterium ◽

Affinity Purification ◽

Glycosyl Hydrolases ◽

Gut Epithelium ◽

Obligate Anaerobic ◽

Hospital Patients ◽

Β Sheet ◽

Antibiotic Associated Diarrhoea

CotE is a coat protein that is present in the spores of Clostridium difficile, an obligate anaerobic bacterium and a pathogen that is a leading cause of antibiotic-associated diarrhoea in hospital patients. Spores serve as the agents of disease transmission, and CotE has been implicated in their attachment to the gut epithelium and subsequent colonization of the host. CotE consists of an N-terminal peroxiredoxin domain and a C-terminal chitinase domain. Here, a C-terminal fragment of CotE comprising residues 349–712 has been crystallized and its structure has been determined to reveal a core eight-stranded β-barrel fold with a neighbouring subdomain containing a five-stranded β-sheet. A prominent groove running across the top of the barrel is lined by residues that are conserved in family 18 glycosyl hydrolases and which participate in catalysis. Electron density identified in the groove defines the pentapeptide Gly-Pro-Ala-Met-Lys derived from the N-terminus of the protein following proteolytic cleavage to remove an affinity-purification tag. These observations suggest the possibility of designing peptidomimetics to block C. difficile transmission.

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