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__NOTOC__
__NOTOC__
{{Clostridium difficile}}
{{Siren|Clostridium difficile infection}}
{{Clostridium difficile infection}}
{{CMG}}
{{CMG}}
==Overview==
The most important risk factor for the development of ''C. difficile'' infection is antibiotic use within the past 12 weeks. Although ''C. difficile'' infection has been described with almost all antibiotics, ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones are most classically and most commonly associated with development of ''C. difficile'' infection. Other important risk factors include recent hospitalization (< 12 weeks), advanced age (>65 years), immunodeficiency (primary or secondary causes), inflammatory bowel disease, and exposure to colonized/infected individuals. The association between gastric acid suppression and ''C. difficile'' infection has not been well established.


==Risk Factors==
==Common Risk Factors==
* Most antibiotics, including metronidazole, can be associated with ''C. diff'' infection, though the most commonly implicated are ampicillin, clindamycin, and the cephalosporins. Antibiotics only rarely associated with infection include parenteral antibiotics, tetracyclines, chloramphenicol, metronidazole and vancomycin.  Onset is usually during or shortly after a course of antibiotics.
===Antibiotic Use===
* Patients who have been staying long-term in a hospital or a nursing home have a higher likelihood of being [[Colony (biology)|colonized]] by this bacterium.  Hospitalized patients are more likely to infected if their roommates are infected.  ''C. diff'' can be cultured from many surfaces in the hospital room, and spores have been identified everywhere, including toilets, floors, mops, scales, furniture, etc.  Health care workers commonly carry the organism on their hands, clothing and stethoscopes, though they are not usually fecal carriers.
'''The most important risk factor is antibiotic use within the past 12 weeks'''.<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507  }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418  }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259  }} </ref> Although ''C. difficile'' infection has been described with almost all antibiotics, the following antibiotics are most classically and most commonly associated with development of ''C. difficile'' infection<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507  }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418  }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259  }} </ref>:
* Hospital outbreaks are common.
*[[Ampicillin]]
* Newborns are often infected, but are asymptomatic.  By 24 months of age, over half of toddlers have immunoglobulins to toxins A and B.
*[[Amoxicillin]]
*[[Cephalosporins]]
*[[Clindamycin]]
*[[Fluoroquinolones]]
===Hospitalization and Long-Term Care Facilities===
*The majority of ''C. difficile'' infections are hospital-acquired.
*The risk associated with hospitalization may persist up to 12 weeks following index hospitalization.<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507 }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418  }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259  }} </ref>
===Advanced Age===
*Elderly patients > 65 years have an approximately 8-fold increased risk of developing ''C. difficile'' infection compared with younger adults.<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507  }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418  }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259 }} </ref>
===Environmental Contamination===
*Exposure to infected or colonized host increases the risk of ''C. difficile infection''.<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507  }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418  }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259 }} </ref>
===Immunodeficiency===
*Immunodeficiency results in inadequate host immune responses that normally prevent the vegetation and growth of ''C. difficile''.<ref name="pmid23780507">{{cite journal| author=Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al.| title=Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. | journal=JAMA Intern Med | year= 2013 | volume= 173 | issue= 14 | pages= 1359-67 | pmid=23780507 | doi=10.1001/jamainternmed.2013.7056 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23780507  }} </ref><ref name="pmid19457418">{{cite journal| author=Leffler DA, Lamont JT| title=Treatment of Clostridium difficile-associated disease. | journal=Gastroenterology | year= 2009 | volume= 136 | issue= 6 | pages= 1899-912 | pmid=19457418 | doi=10.1053/j.gastro.2008.12.070 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19457418 }} </ref><ref name="pmid25875259">{{cite journal| author=Leffler DA, Lamont JT| title=Clostridium difficile infection. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 16 | pages= 1539-48 | pmid=25875259 | doi=10.1056/NEJMra1403772 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25875259  }} </ref>
 
*Immunodeficiency may be primary or secondary. Secondary causes of immunodeficiency include chemotherapy, organ transplant and use of immunosuppressive therapy, or HIV.
 
===Inflammatory Bowel Disease===
* Inflammatory bowel disease (either Crohn's disease or ulcerative colitis) is significantly associated with increased risk of ''C. difficile'' infection.
* Hospitalized patients with IBD flare-up should always undergo diagnostic testing for ''C. difficile'' infection.  
 
===Acid Suppression===
*There are multiple reports of increased risk of ''C. difficile'' infection with gastric acid suppression.<ref name="pmid16414946">{{cite journal| author=Dial S, Delaney JA, Barkun AN, Suissa S| title=Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. | journal=JAMA | year= 2005 | volume= 294 | issue= 23 | pages= 2989-95 | pmid=16414946 | doi=10.1001/jama.294.23.2989 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16414946 }} </ref>
*Nonetheless, the true association between gastric acid suppression and ''C. difficile'' infection is yet to be discovered, since '"C. difficile'' spores are acid-resistant, and any reduction in gastric acidity may not necessarily be associated with increased risk of infection.''
 
==Risk Factors by Organ System==
{| style="width:80%; height:100px" border="1"
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
| style="width:75%" bgcolor="Beige" ; border="1" | No underlying causes
|-
| bgcolor="LightSteelBlue" | '''Chemical/Poisoning'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| bgcolor="Beige" | [[Ampicillin]], [[Amoxicillin]], [[Aztreonam]], [[Bacitracin]], [[Carbapenem]], [[Cefotaxime sodium]], [[Cefprozil]], [[Cefotetan disodium]], [[Cefuroxime]], [[Chloramphenicol]], [[Clindamycin]], [[Daptomycin]], [[Doripenem]], [[Lincomycin Hydrochloride]], [[Meropenem]], [[Metronidazole]], [[Mupirocin]], [[Quinupristin dalfopristin]], [[Rifabutin]], [[Nitrofurantoin]], [[Oritavancin]], [[Pantoprazole]], [[Piperacillin]], [[Rifampin]], [[Streptomycin]], [[Sulfamethoxazole/Trimethoprim (oral)]], [[Sulfamethoxazole]], [[Tedizolid]], [[Teicoplanin]], [[Tetracycline]], [[Tigecycline]], [[Trimethoprim]]
|-
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| bgcolor="Beige" | No underlying causes
|-
|}
 
===Causes in Alphabetical Order===
 
{{col-begin|width=80%}}
{{col-break|width=33%}}
* [[Amoxicillin]]
* [[Cefprozil]]
* [[Cefotetan disodium]]
* [[Doripenem]]
* [[Oritavancin]]
* [[Tigecycline]]
 
{{col-break|width=33%}}
 
 
{{col-break|width=33%}}
 
{{col-end}}


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Needs content]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Needs overview]]
[[Category:Needs causes]]
 
[[Category:Bacterial diseases]]
 
{{WH}}
{{WS}}

Latest revision as of 17:26, 18 September 2017

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Risk calculators and risk factors for Clostridium difficile infection risk factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The most important risk factor for the development of C. difficile infection is antibiotic use within the past 12 weeks. Although C. difficile infection has been described with almost all antibiotics, ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones are most classically and most commonly associated with development of C. difficile infection. Other important risk factors include recent hospitalization (< 12 weeks), advanced age (>65 years), immunodeficiency (primary or secondary causes), inflammatory bowel disease, and exposure to colonized/infected individuals. The association between gastric acid suppression and C. difficile infection has not been well established.

Common Risk Factors

Antibiotic Use

The most important risk factor is antibiotic use within the past 12 weeks.[1][2][3] Although C. difficile infection has been described with almost all antibiotics, the following antibiotics are most classically and most commonly associated with development of C. difficile infection[1][2][3]:

Hospitalization and Long-Term Care Facilities

  • The majority of C. difficile infections are hospital-acquired.
  • The risk associated with hospitalization may persist up to 12 weeks following index hospitalization.[1][2][3]

Advanced Age

  • Elderly patients > 65 years have an approximately 8-fold increased risk of developing C. difficile infection compared with younger adults.[1][2][3]

Environmental Contamination

  • Exposure to infected or colonized host increases the risk of C. difficile infection.[1][2][3]

Immunodeficiency

  • Immunodeficiency results in inadequate host immune responses that normally prevent the vegetation and growth of C. difficile.[1][2][3]
  • Immunodeficiency may be primary or secondary. Secondary causes of immunodeficiency include chemotherapy, organ transplant and use of immunosuppressive therapy, or HIV.

Inflammatory Bowel Disease

  • Inflammatory bowel disease (either Crohn's disease or ulcerative colitis) is significantly associated with increased risk of C. difficile infection.
  • Hospitalized patients with IBD flare-up should always undergo diagnostic testing for C. difficile infection.

Acid Suppression

  • There are multiple reports of increased risk of C. difficile infection with gastric acid suppression.[4]
  • Nonetheless, the true association between gastric acid suppression and C. difficile infection is yet to be discovered, since '"C. difficile spores are acid-resistant, and any reduction in gastric acidity may not necessarily be associated with increased risk of infection.

Risk Factors by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect Ampicillin, Amoxicillin, Aztreonam, Bacitracin, Carbapenem, Cefotaxime sodium, Cefprozil, Cefotetan disodium, Cefuroxime, Chloramphenicol, Clindamycin, Daptomycin, Doripenem, Lincomycin Hydrochloride, Meropenem, Metronidazole, Mupirocin, Quinupristin dalfopristin, Rifabutin, Nitrofurantoin, Oritavancin, Pantoprazole, Piperacillin, Rifampin, Streptomycin, Sulfamethoxazole/Trimethoprim (oral), Sulfamethoxazole, Tedizolid, Teicoplanin, Tetracycline, Tigecycline, Trimethoprim
Ear Nose Throat No underlying causes
Endocrine No underlying causes
Environmental No underlying causes
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease No underlying causes
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C; et al. (2013). "Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011". JAMA Intern Med. 173 (14): 1359–67. doi:10.1001/jamainternmed.2013.7056. PMID 23780507.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Leffler DA, Lamont JT (2009). "Treatment of Clostridium difficile-associated disease". Gastroenterology. 136 (6): 1899–912. doi:10.1053/j.gastro.2008.12.070. PMID 19457418.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Leffler DA, Lamont JT (2015). "Clostridium difficile infection". N Engl J Med. 372 (16): 1539–48. doi:10.1056/NEJMra1403772. PMID 25875259.
  4. ↑ Dial S, Delaney JA, Barkun AN, Suissa S (2005). "Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease". JAMA. 294 (23): 2989–95. doi:10.1001/jama.294.23.2989. PMID 16414946.

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