Clostridium difficile: Difference between revisions
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==Background== | ==Background== | ||
*[[Clostridium]] is a genus of [[Gram-positive bacteria]] | *[[Clostridium]] is a genus of [[Gram-positive bacteria]] | ||
*Most common cause of infectious diarrhea in hospitalized | *Most common cause of infectious diarrhea in hospitalized patients | ||
*Use contact isolation if suspect | *Use contact isolation if suspect | ||
*Alcohol-based hand sanitizers does not reduce spore, but good hand washing does<ref>Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.</ref> | *Alcohol-based hand sanitizers does not reduce spore, but good hand washing does<ref>Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.</ref> | ||
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===Risk factors (pseudomembranous colitis)=== | ===Risk factors (pseudomembranous colitis)=== | ||
*Recent | *Recent antibiotic use (any) | ||
*GI surgery | *GI surgery | ||
*Severe underlying medical illness | *Severe underlying medical illness | ||
*Chemo | *Chemo | ||
*Elderly | *Elderly | ||
===Pediatrics=== | |||
*Testing in infants < 1 year of age not recommended due to high rates of colonization | |||
**~40% of infants < 1 month are colonized and asymptomatic<ref>Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. Jangi S, Lamont JT. J Pediatr Gastroenterol Nutr. 2010 Jul; 51(1):2-7.</ref> | |||
**~15% in infants 6-12 months | |||
**By 2 years of age, normal flora is established, similar to adults<ref>Clostridium difficile Infection in children. Sammons JS, Toltzis P, Zaoutis TE. JAMA Pediatr. 2013 Jun; 167(6):567-73.</ref> | |||
*Risk factors for pediatrics | |||
**Antibiotic exposure, particularly penicillins, cephalosporins, clindamycin, fluoroquinolones | |||
**PPIs | |||
**GI feeding tubes | |||
**Comorbidities - cancer, recent surgery, hospitalizations | |||
==Clinical Features== | ==Clinical Features== | ||
===History=== | ===History=== | ||
*[[Diarrhea]] that develops during antibiotic use or | *[[Diarrhea]] that develops during antibiotic use or within 2 weeks of discontinuation | ||
*Usually occurs after 7-10 days of antibiotics, as diarrhea before that time is more often poor tolerance to antibiotic | |||
*Recent discharge from hospital | *Recent discharge from hospital | ||
*Profuse watery diarrhea | *Profuse watery diarrhea | ||
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*[[Fever]] | *[[Fever]] | ||
*Leukocytosis | *Leukocytosis | ||
*+Fecal leukocytes (distinguishes from benign forms of | *+Fecal leukocytes (distinguishes from benign forms of antibiotic-induced diarrhea) | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
{{Diarrhea DDX}} | {{Diarrhea DDX}} | ||
== | ==Evaluation== | ||
===Labs=== | ===Labs=== | ||
*C. diff toxin assay | *C. diff toxin assay | ||
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*'''Low''' suspicion | *'''Low''' suspicion | ||
**Send stool for C. diff toxin assay | **Send stool for C. diff toxin assay | ||
***Positive | ***Positive → treat (no further testing indicated) | ||
***Negative | ***Negative → do not treat (no further testing indicated) | ||
*'''High''' suspicion | *'''High''' suspicion | ||
**Send stool for C. diff toxin assay AND treat empirically | **Send stool for C. diff toxin assay AND treat empirically | ||
***Positive | ***Positive → treat (no further testing indicated) | ||
***Negative | ***Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea | ||
===Repeat testing=== | ===Repeat testing=== | ||
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*NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test) | *NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test) | ||
== | ==Management== | ||
===Asymptomatic=== | ===Asymptomatic=== | ||
*No diagnostic testing or treatment required<ref>Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.</ref> | *No diagnostic testing or treatment required<ref>Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.</ref> | ||
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'''Criteria:'''<ref name="IDSA">IDSA Guidelines [http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf PDF]</ref><ref>ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/</ref> | '''Criteria:'''<ref name="IDSA">IDSA Guidelines [http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf PDF]</ref><ref>ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/</ref> | ||
*Serum lactate levels >2.2 mmol/l | *Serum lactate levels >2.2 mmol/l | ||
*Hypotension with or without required use of vasopressors | *[[Hypotension]] with or without required use of vasopressors | ||
*Ileus or significant abdominal distention | *[[Ileus]] or significant abdominal distention | ||
*Mental status changes | *Mental status changes | ||
*WBC ≥35,000 cells/mm3 or <2,000 cells/mm3 | *WBC ≥35,000 cells/mm3 or <2,000 cells/mm3 | ||
*Patient requiring ICU admission | *Patient requiring ICU admission | ||
*End organ failure (mechanical ventilation, renal failure, etc.) | *End organ failure (mechanical ventilation, renal failure, etc.) | ||
==== | ====Management==== | ||
{{Severe Cdiff Antibiotics}} | {{Severe Cdiff Antibiotics}} | ||
*Emergency colectomy should be considered if: | *Emergency colectomy should be considered if: | ||
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**Otherwise consider other (more common) causes | **Otherwise consider other (more common) causes | ||
*Antimicrobial resistance is not clinically problematic, first recurrence treated with the same agent used to treat the initial episode | *Antimicrobial resistance is not clinically problematic, first recurrence treated with the same agent used to treat the initial episode | ||
*2nd recurrence - tapered vancomycin with pulse doses | |||
*3rd recurrence - PO vancomycin 10-14 days followed immediately by rifaximin "chaser" 400mg TID x20 days <ref>Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157</ref> | |||
*Other options: | |||
**[[IVIG]] | |||
**Fecal transplant | |||
**Fidamoxicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 weeks after treatment (~15% vs 25%) <ref>Louie TJ et al. Fidaxomicin versus [[Vancomycin]] for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.</ref> | |||
===Pediatrics=== | |||
*Stop offending antimicrobial agents, if possible | |||
*Initial occurrence and first recurrence of mild-moderate disease:<ref>D'Ostroph AR and So TY. Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value. Infect Drug Resist. 2017; 10: 365–375.</ref> | |||
**PO metronidazole 30 mg/kg/d in four divided doses, max 2 g/day | |||
*Severe infection or second recurrence: | |||
**PO vancomycin 40 mg/kg/d in four divided doses, max 500 mg/day | |||
**If no improvement after 24-48 hours, oral vancomycin max dose may be increased to 2 g/d | |||
**Q6hr IV metronidazole, 30 mg/kg/d, may be added to intracolonic/enema vancomycin for ileus, inability to tolerate PO antibiotics | |||
***1-3 year old -- 250 mg vancomycin in 50 mL NS | |||
***4-9 year old -- 375 mg vancomycin in 75 mL NS | |||
***> 9 year old -- 500 mg vancomycin in 100 mL NS | |||
*Multiple recurrences, other strategies, in consult with pediatric GI: | |||
**May benefit from tapering and pulse oral vancomycin over 1.5-2 months, as done in adults | |||
**Consider PO fidaxomicin in ≥ 6 year old patients at 200 mg twice daily for 10 dats | |||
===[[Antibiotic Sensitivities]]<ref>Sanford Guide to Antimicrobial Therapy 2014</ref>=== | ===[[Antibiotic Sensitivities]]<ref>Sanford Guide to Antimicrobial Therapy 2014</ref>=== |
Revision as of 13:28, 30 March 2019
Background
- Clostridium is a genus of Gram-positive bacteria
- Most common cause of infectious diarrhea in hospitalized patients
- Use contact isolation if suspect
- Alcohol-based hand sanitizers does not reduce spore, but good hand washing does[1]
- 60-70% of infants are asymptomatic carriers of c diff[2]
Risk factors (pseudomembranous colitis)
- Recent antibiotic use (any)
- GI surgery
- Severe underlying medical illness
- Chemo
- Elderly
Pediatrics
- Testing in infants < 1 year of age not recommended due to high rates of colonization
- Risk factors for pediatrics
- Antibiotic exposure, particularly penicillins, cephalosporins, clindamycin, fluoroquinolones
- PPIs
- GI feeding tubes
- Comorbidities - cancer, recent surgery, hospitalizations
Clinical Features
History
- Diarrhea that develops during antibiotic use or within 2 weeks of discontinuation
- Usually occurs after 7-10 days of antibiotics, as diarrhea before that time is more often poor tolerance to antibiotic
- Recent discharge from hospital
- Profuse watery diarrhea
Exam
- Abdominal pain
- Fever
- Leukocytosis
- +Fecal leukocytes (distinguishes from benign forms of antibiotic-induced diarrhea)
Differential Diagnosis
Acute diarrhea
Infectious
- Viral (e.g. rotavirus)
- Bacterial
- Campylobacter
- Shigella
- Salmonella (non-typhi)
- Escherichia coli
- E. coli 0157:H7
- Yersinia enterocolitica
- Vibrio cholerae
- Clostridium difficile
- Parasitic
- Toxin
Noninfectious
- GI Bleed
- Appendicitis
- Mesenteric Ischemia
- Diverticulitis
- Adrenal Crisis
- Thyroid Storm
- Toxicologic exposures
- Antibiotic or drug-associated
Watery Diarrhea
- Enterotoxigenic E. coli (most common cause of watery diarrhea)[5]
- Norovirus (often has prominent vomiting)
- Campylobacter
- Non-typhoidal Salmonella
- Enteroaggregative E. coli (EAEC)
- Enterotoxigenic Bacteroides fragilis
Traveler's Diarrhea
Evaluation
Labs
- C. diff toxin assay
- Sn 63-94%, Sp 75-100%
- Culture
- Positive culture only means C. diff present, not necessarily that it is causing disease
Testing Algorithm
For patients with suspected Clostridium difficile associated diarrhea (CDAD)
- Low suspicion
- Send stool for C. diff toxin assay
- Positive → treat (no further testing indicated)
- Negative → do not treat (no further testing indicated)
- Send stool for C. diff toxin assay
- High suspicion
- Send stool for C. diff toxin assay AND treat empirically
- Positive → treat (no further testing indicated)
- Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea
- Send stool for C. diff toxin assay AND treat empirically
Repeat testing
- Never a need for repeat testing within 7 days of a previous test
- NO NEED to repeat positive tests as symptoms resolve as a “test of cure”
- NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test)
Management
Asymptomatic
- No diagnostic testing or treatment required[6]
Mild
- Either discontinue offending antibiotics(if possible) or give Metronidazole 500mg PO q6hr x10-14d
Moderate
- Vancomycin 125 mg PO four times daily for 10 days
- Fidaxomicin 200 mg PO two times daily for 10 days
- Metronidazole 500mg PO or IV four times daily for 10 days (third line therapy)
Severe
- Serum lactate levels >2.2 mmol/l
- Hypotension with or without required use of vasopressors
- Ileus or significant abdominal distention
- Mental status changes
- WBC ≥35,000 cells/mm3 or <2,000 cells/mm3
- Patient requiring ICU admission
- End organ failure (mechanical ventilation, renal failure, etc.)
Management
- Vancomycin 125 mg PO four times daily for 10 days
- Fidaxomicin 200 mg PO two times daily for 10 days
- Emergency colectomy should be considered if:
- WBC >20K
- Lactate >5
- Age >75
- Immunosuppression
- Toxic megacolon
- Colonic perforation
- Multi-organ system failure
Recurrent Infection
- Relapse occurs in 10-25% of patients
- Occurs <=4 weeks after the completion of therapy
- Otherwise consider other (more common) causes
- Antimicrobial resistance is not clinically problematic, first recurrence treated with the same agent used to treat the initial episode
- 2nd recurrence - tapered vancomycin with pulse doses
- 3rd recurrence - PO vancomycin 10-14 days followed immediately by rifaximin "chaser" 400mg TID x20 days [9]
- Other options:
Pediatrics
- Stop offending antimicrobial agents, if possible
- Initial occurrence and first recurrence of mild-moderate disease:[11]
- PO metronidazole 30 mg/kg/d in four divided doses, max 2 g/day
- Severe infection or second recurrence:
- PO vancomycin 40 mg/kg/d in four divided doses, max 500 mg/day
- If no improvement after 24-48 hours, oral vancomycin max dose may be increased to 2 g/d
- Q6hr IV metronidazole, 30 mg/kg/d, may be added to intracolonic/enema vancomycin for ileus, inability to tolerate PO antibiotics
- 1-3 year old -- 250 mg vancomycin in 50 mL NS
- 4-9 year old -- 375 mg vancomycin in 75 mL NS
- > 9 year old -- 500 mg vancomycin in 100 mL NS
- Multiple recurrences, other strategies, in consult with pediatric GI:
- May benefit from tapering and pulse oral vancomycin over 1.5-2 months, as done in adults
- Consider PO fidaxomicin in ≥ 6 year old patients at 200 mg twice daily for 10 dats
Antibiotic Sensitivities[12]
Disposition
- Admit:
- Severe diarrhea
- Outpatient antibiotic failure
- Systemic response (fever, leukocytosis, severe abdominal pain)
See Also
References
- ↑ Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
- ↑ Jangi S and Lamon JT. Asymptomatic colonization by Clostridium difficile: implications for disease in later life. J Pediatr Gastroenterol Nutr. 2010; 51(1):2-7.
- ↑ Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. Jangi S, Lamont JT. J Pediatr Gastroenterol Nutr. 2010 Jul; 51(1):2-7.
- ↑ Clostridium difficile Infection in children. Sammons JS, Toltzis P, Zaoutis TE. JAMA Pediatr. 2013 Jun; 167(6):567-73.
- ↑ Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
- ↑ Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
- ↑ IDSA Guidelines PDF
- ↑ ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/
- ↑ Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157
- ↑ Louie TJ et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.
- ↑ D'Ostroph AR and So TY. Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value. Infect Drug Resist. 2017; 10: 365–375.
- ↑ Sanford Guide to Antimicrobial Therapy 2014