Clostridium difficile infection medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Clostridium difficile}}
{{Clostridium difficile}}
{{CMG}}
{{CMG}}; {{AE}} {{GRN}}


==Overview==
==Overview==
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Patients should be treated as soon as possible when the diagnosis of ''Clostridium difficile'' colitis (CDC) is made to avoid frank [[sepsis]] or bowel perforation.
Patients should be treated as soon as possible when the diagnosis of ''Clostridium difficile'' colitis (CDC) is made to avoid frank [[sepsis]] or bowel perforation.
==Principles of Therapy for ''Clostridium difficile'' infection==
#If a patient has a strong pre-test probability for CDI, empiric therapy should be considered regardless of the laboratory testing result<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 |pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>. CDI accounts for about 20% of antibiotic-associated diarrhoea cases in the USA<ref name="Planche2013">{{cite journal|last1=Planche|first1=Tim|title=Clostridium difficile|journal=Medicine|volume=41|issue=11|year=2013|pages=654–657|issn=13573039|doi=10.1016/j.mpmed.2013.08.003}}</ref>.The main risk factors for CDI are:
##Antibiotic exposure and the first three months after cessation of antibiotics<ref name="pmid22146873">{{cite journal| author=Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ| title=Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. | journal=J Antimicrob Chemother | year= 2012 | volume= 67 | issue= 3 | pages= 742-8 | pmid=22146873 | doi=10.1093/jac/dkr508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22146873  }} </ref>. Commonly [[clindamycin]], [[penicillins]], [[cephalosporins]], [[fluoroquinolones]],and multiple antibiotics<ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref>.
##Exposure to '''''Clostridium difficile''''': up to 25% of hospitalized patients and residents of lonf term facilities are colonized<ref name="Planche2013">{{cite journal|last1=Planche|first1=Tim|title=Clostridium difficile|journal=Medicine|volume=41|issue=11|year=2013|pages=654–657|issn=13573039|doi=10.1016/j.mpmed.2013.08.003}}</ref>.
##Age >65<ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref>.
##History of [[inflammatory bowel disease]]<ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref>.
#Any antimicrobial agent should be discontinued<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. |journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.
#Current guidelines recommend to choose the treatment regimen based on the severity of the disease<ref name="pmid20307191">{{cite journal|author=Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al.| title=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). |journal=Infect Control Hosp Epidemiol | year= 2010 | volume= 31 | issue= 5 | pages= 431-55 | pmid=20307191 | doi=10.1086/651706 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20307191  }} </ref> <ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 |pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref><ref name="Planche2013">{{cite journal|last1=Planche|first1=Tim|title=Clostridium difficile|journal=Medicine|volume=41|issue=11|year=2013|pages=654–657|issn=13573039|doi=10.1016/j.mpmed.2013.08.003}}</ref><ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref>:
##Mild: diarrhea as the only symptom.
##Moderate:  raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline.
##Severe: leucocytosis >15,000 cells/mL OR serum creatinene level >1.5 times baseline or  abdominal tenderness and serum albumin < 3 g/dL.
##Severe complicated: hypotension or shock, ileus, megacolon, leucocytosis >20,000 cells/mL OR leucopenia <2,000, lactate >2.2 mmol/L, delirium, fever ≥ 38.5 °C, organ failure.
#Duration: recommendations stablish a 10-14 days treatment. If clinical response in 5-7 days, complete 10 days<ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref>.
#Do not use metronidazole beyond the first recurrence episode of CDI or for long-term therapy because of the risk of neurotoxicity<ref name="pmid20307191">{{cite journal|author=Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al.| title=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). |journal=Infect Control Hosp Epidemiol | year= 2010 | volume= 31 | issue= 5 | pages= 431-55 | pmid=20307191 | doi=10.1086/651706 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20307191  }} </ref>.
#For mild-to-moderate patients who are intolerant/allergic to metronidazole and for pregnant/breastfeeding women, vancomycin should be used at standard dosing<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 |volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.
#The use of anti-peristaltic agents to control diarrhea from confirmed or suspected CDI should be limited or avoided<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.
#Supportive care should be delivered to all patients with severe or severe complicated CDI<ref name="pmid23439232">{{cite journal|author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 |pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.
#CT scanning of the abdomen and pelvis is recommended in patients with severe complicated CDI<ref name="pmid23439232">{{cite journal|author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 |pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.
#Surgical consult should be obtained in all patients with complicated CDI<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 |pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }}</ref>.
#If there is a third recurrence after a pulsed vancomycin regimen, fecal microbiota transplant should be considered<ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 | pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref>.


==Medical Therapy==
==Medical Therapy==
Three antibiotics are effective against ''C. difficile''.  
<font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font><ref name="pmid23439232">{{cite journal| author=Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH et al.| title=Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. | journal=Am J Gastroenterol | year= 2013 | volume= 108 | issue= 4 |pages= 478-98; quiz 499 | pmid=23439232 | doi=10.1038/ajg.2013.4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439232  }} </ref><ref name="pmid20307191">{{cite journal|author=Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al.| title=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). |journal=Infect Control Hosp Epidemiol | year= 2010 | volume= 31 | issue= 5 | pages= 431-55 | pmid=20307191 | doi=10.1086/651706 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20307191  }} </ref><ref name="Planche2013">{{cite journal|last1=Planche|first1=Tim|title=Clostridium difficile|journal=Medicine|volume=41|issue=11|year=2013|pages=654–657|issn=13573039|doi=10.1016/j.mpmed.2013.08.003}}</ref><ref name="KnightSurawicz2013">{{cite journal|last1=Knight|first1=Christopher L.|last2=Surawicz|first2=Christina M.|title=Clostridium difficile Infection|journal=Medical Clinics of North America|volume=97|issue=4|year=2013|pages=523–536|issn=00257125|doi=10.1016/j.mcna.2013.02.003}}</ref><ref name="pmid18971494">{{cite journal| author=Kelly CP, LaMont JT| title=Clostridium difficile--more difficult than ever. | journal=N Engl J Med |year= 2008 | volume= 359 | issue= 18 | pages= 1932-40 | pmid=18971494 | doi=10.1056/NEJMra0707500 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18971494  }} </ref>
*[[Metronidazole]] 500mg orally three times daily is the drug of choice, because of superior tolerability, lower price and comparable efficacy<ref name="pmid6138597">Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov 5;2(8358):1043-6. PMID 6138597</ref>. Metronidazole is taken up by the GI tract, unlike vancomycin. Some therefore recommend prescriptions of severe cases with vancomycin, to insure adequate levels. IV metronidazole 500 mg TID is also effective.
{|
*Oral [[vancomycin]] 125 mg four times daily is second-line therapy, but is avoided due to theoretical concerns of converting intestinal flora into vancomycin resistant organisms. However, it is used in the following cases: severe ''C. difficile'' diarrhea<ref name="pmid17599306">{{cite journal |author=Zar FA, Bakkanagari SR, Moorthi KM, Davis MB |title=A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity |journal=Clin. Infect. Dis. |volume=45 |issue=3 |pages=302–7 |year=2007 |pmid=17599306 |doi=10.1086/519265}}</ref> (the duration of diarrhea is reduced to 3 versus 4.6 days with metronidazole; no response to oral metronidazole; the organism is resistant to metronidazole; the patient is allergic to metronidazole; the patient is either pregnant or younger than 10 years of age. Vancomycin must be administered orally because IV administration does not achieve gut lumen minimum therapeutic concentration.  
 
*The use of [[linezolid]] may be considered too.
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'''Initial episode'''
 
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&nbsp;&nbsp;▸&nbsp;&nbsp;'''Mild to moderate'''
 
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&nbsp;&nbsp;▸&nbsp;&nbsp;'''Severe'''
 
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&nbsp;&nbsp;▸&nbsp;&nbsp;'''Severe complicated'''
 
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'''Recurrence'''
 
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&nbsp;&nbsp;▸&nbsp;&nbsp;'''First recurrence'''
 
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&nbsp;&nbsp;▸&nbsp;&nbsp;'''Second recurrence'''
 
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! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center| {{fontcolor|#FFF|Mild to moderate}}
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Recommended treatment'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Metronidazole]] 500 mg orally q8h'''''
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''If no improvement in 5-7 days'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Vancomycin]] 125 mg orally q6h'''''
 
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! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center| {{fontcolor|#FFF|Severe}}
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Recommended treatment'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Vancomycin]] 125 mg orally q6h'''''
 
|-
 
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| valign=top |
 
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
 
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center| {{fontcolor|#FFF|Severe complicated}}
 
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| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Recommended treatment'''''<sup>†</sup>
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Vancomycin]] 500 mg orally q6h'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | PLUS
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Metronidazole]] 500 mg IV q8h'''''
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=left | <SMALL><sup>†</sup> If '''''[[ileus]]''''' present, add'''''[[Vancomycin]] 500 mg in 100 mL NS per rectum q6h as retention enema'''''.</SMALL>
 
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
 
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center| {{fontcolor|#FFF|First recurrence}}
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | Recommended treatment'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''Same as first episode but stratified by severity'''''
 
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
 
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center| {{fontcolor|#FFF|Second recurrence}}
 
|-
 
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Recommended treatment'''''
 
|-
 
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''''[[Vancomycin]] in tapered and pulsed doses'''''
 
      125 mg 4 times daily for 14 days
 
      125 mg 2 times daily for 7 days
 
      125 mg once daily for 7 days
 
      125 mg once every 2 days for 8 days (4 doses)


It has been known that drugs traditionally used to stop diarrhea worsen the course of ''C. difficile''-related pseudomembranous colitis. [[Loperamide]], [[diphenoxylate]] and [[bismuth]] compounds are indeed contraindicated, because slowing of fecal transit time is thought to result in extended toxin-associated damage. [[Cholestyramine]], a powder drink occasionally used to lower cholesterol, is effective in binding both Toxin A and B, and slows bowel motility and helps prevent dehydration.<ref name=Stroehlein_2004>{{cite journal |author=Stroehlein J |title=Treatment of ''Clostridium difficile'' Infection |journal=Curr Treat Options Gastroenterol |volume=7 |issue=3 |pages=235-239 |year=2004 |pmid=15149585}}</ref> The dosage can be 4 grams daily, to up to four doses a day: caution should be exercised to prevent constipation, or drug interactions, most notably the binding of drugs by cholestyramine, preventing their absorption. A last-resort treatment in [[immunosuppression|immunosuppressed]] patients is [[intravenous immunoglobulin]] (IVIG).<ref name=Stroehlein_2004 />
      125 mg once every 3 days for 15 days (5 doses)


[[Pseudomembranous colitis]] caused by ''C. difficile'' is treated with antibiotics, for example, [[vancomycin]], [[metronidazole]], bacitracin or fusidic acid.
|-


Patients should be treated for 10-14 days, unless the inciting antibiotics can’t be discontinued, in which case metronidazole or vancomycin should be continued for a week or so after discontinuation of the inciting antibiotics.
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Failure to initially respond is typically not due to resistance, but may be due to misdiagnosis, noncompliance or other GI disease.


Up to 15-20% of patients will [[relapse]] after treatment, not typically due to resistant organisms. The exact mechanism has not been clarified; these patients often do not develop as prominent an antibody response, so immune mediated defects may be contributory.  Relapse usually is within a few days of discontinued prescription, though may be as long as 30 days afterward. For relapse, patients should receive a second course of metronidazole for 14 days. For a second relapse, a ''C. diff'' titer should be checked to confirm the diagnosis, and then a third course of antibiotics should be with vancomycin. For patients with multiple relapses, some recommend a schedule of tapering vancomycin, from full dose down to 125 mg q3 days over the course of 6 weeks. Other potential prescriptions that are not commonly used include prescriptions with [[cholestyramine]], which binds the toxin (but will also bind vancomycin), and attempts to repopulate the gut with organisms.
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===Fecal Bacteriotherapy===
===Fecal Bacteriotherapy===
[[Fecal bacteriotherapy]], a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.<ref name=Schwan_1983>{{cite journal | author = Schwan A, Sjölin S, Trottestam U, Aronsson B | title = Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. | journal = Lancet | volume = 2 | issue = 8354 | pages = 845 | year = 1983 | id = PMID 6137662}}</ref><ref name=Schwan_1994>{{cite journal | author = Paterson D, Iredell J, Whitby M | title = Putting back the bugs: bacterial treatment relieves chronic diarrhoea. | journal = Med J Aust | volume = 160 | issue = 4 | pages = 232-3 | year = 1994 | id = PMID 8309401}}</ref><ref name=Borody_2000>{{cite journal | author = Borody T | title = "Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea. | journal = Am J Gastroenterol | volume = 95 | issue = 11 | pages = 3028-9 | year = 2000 | url = http://www.cdd.com.au/pdf/paper32.pdf | id = PMID 11095314}}</ref>
[[Fecal bacteriotherapy]], a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.<ref name=Schwan_1983>{{cite journal | author = Schwan A, Sjölin S, Trottestam U, Aronsson B | title = Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. | journal = Lancet | volume = 2 | issue = 8354 | pages = 845 | year = 1983 | id = PMID 6137662}}</ref><ref name=Schwan_1994>{{cite journal | author = Paterson D, Iredell J, Whitby M | title = Putting back the bugs: bacterial treatment relieves chronic diarrhoea. | journal = Med J Aust | volume = 160 | issue = 4 | pages = 232-3 | year = 1994 | id = PMID 8309401}}</ref><ref name=Borody_2000>{{cite journal | author = Borody T | title = "Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea. | journal = Am J Gastroenterol | volume = 95 | issue = 11 | pages = 3028-9 | year = 2000 | url = http://www.cdd.com.au/pdf/paper32.pdf | id = PMID 11095314}}</ref>

Revision as of 13:34, 11 June 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Guillermo Rodriguez Nava, M.D. [2]

Overview

Many persons will also be asymptomatic and colonized with Clostridium difficile. Treatment in asymptomatic patients is controversial, also leading into the debate of clinical surveillance and how it intersects with public health policy.

It is possible that mild cases do not need treatment.[1]

Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis (CDC) is made to avoid frank sepsis or bowel perforation.

Principles of Therapy for Clostridium difficile infection

  1. If a patient has a strong pre-test probability for CDI, empiric therapy should be considered regardless of the laboratory testing result[2]. CDI accounts for about 20% of antibiotic-associated diarrhoea cases in the USA[3].The main risk factors for CDI are:
    1. Antibiotic exposure and the first three months after cessation of antibiotics[4]. Commonly clindamycin, penicillins, cephalosporins, fluoroquinolones,and multiple antibiotics[5].
    2. Exposure to Clostridium difficile: up to 25% of hospitalized patients and residents of lonf term facilities are colonized[3].
    3. Age >65[5].
    4. History of inflammatory bowel disease[5].
  2. Any antimicrobial agent should be discontinued[2].
  3. Current guidelines recommend to choose the treatment regimen based on the severity of the disease[6] [2][3][5]:
    1. Mild: diarrhea as the only symptom.
    2. Moderate: raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline.
    3. Severe: leucocytosis >15,000 cells/mL OR serum creatinene level >1.5 times baseline or abdominal tenderness and serum albumin < 3 g/dL.
    4. Severe complicated: hypotension or shock, ileus, megacolon, leucocytosis >20,000 cells/mL OR leucopenia <2,000, lactate >2.2 mmol/L, delirium, fever ≥ 38.5 °C, organ failure.
  4. Duration: recommendations stablish a 10-14 days treatment. If clinical response in 5-7 days, complete 10 days[5].
  5. Do not use metronidazole beyond the first recurrence episode of CDI or for long-term therapy because of the risk of neurotoxicity[6].
  6. For mild-to-moderate patients who are intolerant/allergic to metronidazole and for pregnant/breastfeeding women, vancomycin should be used at standard dosing[2].
  7. The use of anti-peristaltic agents to control diarrhea from confirmed or suspected CDI should be limited or avoided[2].
  8. Supportive care should be delivered to all patients with severe or severe complicated CDI[2].
  9. CT scanning of the abdomen and pelvis is recommended in patients with severe complicated CDI[2].
  10. Surgical consult should be obtained in all patients with complicated CDI[2].
  11. If there is a third recurrence after a pulsed vancomycin regimen, fecal microbiota transplant should be considered[2].

Medical Therapy

▸ Click on the following categories to expand treatment regimens.[2][6][3][5][7]

Initial episode

  ▸  Mild to moderate

  ▸  Severe

  ▸  Severe complicated

Recurrence

  ▸  First recurrence

  ▸  Second recurrence

Mild to moderate
Recommended treatment
▸ Metronidazole 500 mg orally q8h
If no improvement in 5-7 days
▸ Vancomycin 125 mg orally q6h
Severe
Recommended treatment
▸ Vancomycin 125 mg orally q6h
Severe complicated
Recommended treatment†
▸ Vancomycin 500 mg orally q6h
PLUS
▸ Metronidazole 500 mg IV q8h
† If ileus present, addVancomycin 500 mg in 100 mL NS per rectum q6h as retention enema.
First recurrence
Recommended treatment
▸ Same as first episode but stratified by severity
Second recurrence
Recommended treatment
▸ Vancomycin in tapered and pulsed doses 
     125 mg 4 times daily for 14 days

     125 mg 2 times daily for 7 days

     125 mg once daily for 7 days

     125 mg once every 2 days for 8 days (4 doses)

     125 mg once every 3 days for 15 days (5 doses)

Fecal Bacteriotherapy

Fecal bacteriotherapy, a procedure related to probiotic research, has been suggested as a potential cure for the disease. It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. It has a success rate of nearly 95% according to some sources.[8][9][10]

References

  1. ↑ Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004610. PMID 17636768
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH; et al. (2013). "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections". Am J Gastroenterol. 108 (4): 478–98, quiz 499. doi:10.1038/ajg.2013.4. PMID 23439232.
  3. ↑ 3.0 3.1 3.2 3.3 Planche, Tim (2013). "Clostridium difficile". Medicine. 41 (11): 654–657. doi:10.1016/j.mpmed.2013.08.003. ISSN 1357-3039.
  4. ↑ Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ (2012). "Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics". J Antimicrob Chemother. 67 (3): 742–8. doi:10.1093/jac/dkr508. PMID 22146873.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Knight, Christopher L.; Surawicz, Christina M. (2013). "Clostridium difficile Infection". Medical Clinics of North America. 97 (4): 523–536. doi:10.1016/j.mcna.2013.02.003. ISSN 0025-7125.
  6. ↑ 6.0 6.1 6.2 Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC; et al. (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 (5): 431–55. doi:10.1086/651706. PMID 20307191.
  7. ↑ Kelly CP, LaMont JT (2008). "Clostridium difficile--more difficult than ever". N Engl J Med. 359 (18): 1932–40. doi:10.1056/NEJMra0707500. PMID 18971494.
  8. ↑ Schwan A, Sjölin S, Trottestam U, Aronsson B (1983). "Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces". Lancet. 2 (8354): 845. PMID 6137662.
  9. ↑ Paterson D, Iredell J, Whitby M (1994). "Putting back the bugs: bacterial treatment relieves chronic diarrhoea". Med J Aust. 160 (4): 232–3. PMID 8309401.
  10. ↑ Borody T (2000). ""Flora Power"-- fecal bacteria cure chronic C. difficile diarrhea" (PDF). Am J Gastroenterol. 95 (11): 3028–9. PMID 11095314.

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