Clostridium difficile (peds): Difference between revisions

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''This page is for <u>pediatric</u> patients; for adult patients see [[clostridium difficile]].''
''This page is for <u>pediatric</u> patients; for adult patients see [[clostridium difficile]].''
==Background==
[[File:Pseudomembranous colitis 1.jpg|thumb|Pseudomembranous colitis with yellow pseudomembranes seen on the wall of the sigmoid colon.]]
*[[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 do not reduce spores, but good hand washing does<ref>Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.</ref>
===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
**~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==
===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]]
==Differential Diagnosis==
{{Diarrhea DDX}}
==Evaluation==
[[File:MPX1834 synpic40781.png|thumb|Pseudomembranous colitis from ''C. difficile'' on abdominal CT demonstratin diffuse colonic wall thickening and a shaggy endoluminal contour.]]
[[File:PMC5137169 gr1.png|thumb|Pseudomembranous colitis with (A) Accordion sign in transverse colon (thin arrows). (B) Colonic wall thickness, target sign (thick arrow), peritoneal fluid (thin arrow) and pericolonic fat stranding (arrowhead).]]
===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)
*'''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
===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<ref>Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.</ref>
===Mild===
*Either discontinue offending antibiotics (if possible) or give [[metronidazole]] 500mg PO q6hr x10-14d
===Moderate===
{{Moderate Cdiff Antibiotics}}
===Severe===
'''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
*[[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====
{{Severe Cdiff Antibiotics}}
*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 <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>===
{| class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Category'''
| align="center" style="background:#f0f0f0;"|'''Antibiotic'''
| align="center" style="background:#f0f0f0;"|'''Sensitivity'''
|-
| [[Penicillins]]||[[Penicillin G]]||X2
|-
| ||[[Penicillin V]]||X1
|-
| Anti-Staphylocccal [[Penicillins]]||[[Methicillin]]||X1
|-
| ||[[Nafcillin]]/[[Oxacillin]]||X1
|-
| ||[[Cloxacillin]]/[[Diclox.]]||X1
|-
| Amino-[[Penicillins]]||[[AMP]]/[[Amox]]||X1
|-
| ||[[Amox-Clav]]||X1
|-
| ||[[AMP-Sulb]]||X2
|-
| Anti-Pseudomonal [[Penicillins]]||[[Ticarcillin]]||X1
|-
| ||[[Ticar-Clav]]||X1
|-
| ||[[Pip-Tazo]]||X1
|-
| ||[[Piperacillin]]||X2
|-
| [[Carbapenems]]||[[Doripenem]]||X2
|-
| ||[[Ertapenem]]||X2
|-
| ||[[Imipenem]]||X2
|-
| ||[[Meropenem]]||X2
|-
| ||[[Aztreonam]]||R
|-
| [[Fluroquinolones]]||[[Ciprofloxacin]]||R
|-
| ||[[Ofloxacin]]||X1
|-
| ||[[Pefloxacin]]||X1
|-
| ||[[Levofloxacin]]||R
|-
| ||[[Moxifloxacin]]||R
|-
| ||[[Gemifloxacin]]||X1
|-
| ||[[Gatifloxacin]]||R
|-
| 1st G [[Cephalo]]||[[Cefazolin]]||X1
|-
| 2nd G. [[Cephalo]]||[[Cefotetan]]||X1
|-
| ||[[Cefoxitin]]||R
|-
| ||[[Cefuroxime]]||X1
|-
| 3rd/4th G. [[Cephalo]]||[[Cefotaxime]]||R
|-
| ||[[Cefizoxime]]||R
|-
| ||[[CefTRIAXone]]||X1
|-
| ||[[Ceftaroline]]||X1
|-
| ||[[CefTAZidime]]||X1
|-
| ||[[Cefepime]]||R
|-
| Oral 1st G. [[Cephalo]]||[[Cefadroxil]]||X1
|-
| ||[[Cephalexin]]||X1
|-
| Oral 2nd G. [[Cephalo]]||[[Cefaclor]]/[[Loracarbef]]||X1
|-
| ||[[Cefproxil]]||X1
|-
| ||[[Cefuroxime axetil]]||X1
|-
| Oral 3rd G. [[Cephalo]]||[[Cefixime]]||X1
|-
| ||[[Ceftibuten]]||X1
|-
| ||[[Cefpodox]]/[[Cefdinir]]/[[Cefditoren]]||X1
|-
| [[Aminoglycosides]]||[[Gentamicin]]||R
|-
| ||[[Tobramycin]]||R
|-
| ||[[Amikacin]]||R
|-
| ||[[Chloramphenicol]]||I
|-
| ||[[Clindamycin]]||X1
|-
| [[Macrolides]]||[[Erythromycin]]||X1
|-
| ||[[Azithromycin]]||X1
|-
| ||[[Clarithromycin]]||X1
|-
| Ketolide||[[Telithromycin]]||X1
|-
| Tetracyclines||[[Doxycycline]]||X1
|-
| ||[[Minocycline]]||X1
|-
| Glycylcycline||[[Tigecycline]]||X1
|-
| ||[[Daptomycin]]||X1
|-
| Glyco/Lipoclycopeptides||[[Vancomycin]]||'''S'''
|-
| ||[[Teicoplanin]]||'''S'''
|-
| ||[[Telavancin]]||'''S'''
|-
| ||[[Fusidic Acid]]||X1
|-
| ||[[Trimethoprim]]||X1
|-
| ||[[TMP-SMX]]||X1
|-
| Urinary Agents||[[Nitrofurantoin]]||X1
|-
| ||[[Fosfomycin]]||X1
|-
| Other||[[Rifampin]]||X1
|-
| ||[[Metronidazole]]||'''S'''
|-
| ||[[Quinupristin dalfoppristin]]||I
|-
| ||[[Linezolid]]||I
|-
| ||[[Colistimethate]]||X1
|}
==Disposition==
*Admit:
**Severe diarrhea
**Outpatient antibiotic failure
**Systemic response (fever, leukocytosis, severe abdominal pain)
==See Also==
*[[Diarrhea]]
*[[Clostridium]]
==References==
<references/>
[[Category:ID]]
[[Category:GI]]

Revision as of 03:08, 4 July 2019

This page is for pediatric patients; for adult patients see clostridium difficile.

Background

Pseudomembranous colitis with yellow pseudomembranes seen on the wall of the sigmoid colon.
  • 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 do not reduce spores, but good hand washing does[1]

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
    • ~40% of infants < 1 month are colonized and asymptomatic[2]
    • ~15% in infants 6-12 months
    • By 2 years of age, normal flora is established, similar to adults[3]
  • 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

Differential Diagnosis

Acute diarrhea

Infectious

Noninfectious

Watery Diarrhea

Traveler's Diarrhea

Evaluation

Pseudomembranous colitis from C. difficile on abdominal CT demonstratin diffuse colonic wall thickening and a shaggy endoluminal contour.
Pseudomembranous colitis with (A) Accordion sign in transverse colon (thin arrows). (B) Colonic wall thickness, target sign (thick arrow), peritoneal fluid (thin arrow) and pericolonic fat stranding (arrowhead).

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)
  • 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

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[5]

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 three times daily for 10 days (third line therapy)

Severe

Criteria:[6][7]

  • 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 [8]
  • 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%) [9]

Pediatrics

  • Stop offending antimicrobial agents, if possible
  • Initial occurrence and first recurrence of mild-moderate disease:[10]
    • 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[11]

Category Antibiotic Sensitivity
Penicillins Penicillin G X2
Penicillin V X1
Anti-Staphylocccal Penicillins Methicillin X1
Nafcillin/Oxacillin X1
Cloxacillin/Diclox. X1
Amino-Penicillins AMP/Amox X1
Amox-Clav X1
AMP-Sulb X2
Anti-Pseudomonal Penicillins Ticarcillin X1
Ticar-Clav X1
Pip-Tazo X1
Piperacillin X2
Carbapenems Doripenem X2
Ertapenem X2
Imipenem X2
Meropenem X2
Aztreonam R
Fluroquinolones Ciprofloxacin R
Ofloxacin X1
Pefloxacin X1
Levofloxacin R
Moxifloxacin R
Gemifloxacin X1
Gatifloxacin R
1st G Cephalo Cefazolin X1
2nd G. Cephalo Cefotetan X1
Cefoxitin R
Cefuroxime X1
3rd/4th G. Cephalo Cefotaxime R
Cefizoxime R
CefTRIAXone X1
Ceftaroline X1
CefTAZidime X1
Cefepime R
Oral 1st G. Cephalo Cefadroxil X1
Cephalexin X1
Oral 2nd G. Cephalo Cefaclor/Loracarbef X1
Cefproxil X1
Cefuroxime axetil X1
Oral 3rd G. Cephalo Cefixime X1
Ceftibuten X1
Cefpodox/Cefdinir/Cefditoren X1
Aminoglycosides Gentamicin R
Tobramycin R
Amikacin R
Chloramphenicol I
Clindamycin X1
Macrolides Erythromycin X1
Azithromycin X1
Clarithromycin X1
Ketolide Telithromycin X1
Tetracyclines Doxycycline X1
Minocycline X1
Glycylcycline Tigecycline X1
Daptomycin X1
Glyco/Lipoclycopeptides Vancomycin S
Teicoplanin S
Telavancin S
Fusidic Acid X1
Trimethoprim X1
TMP-SMX X1
Urinary Agents Nitrofurantoin X1
Fosfomycin X1
Other Rifampin X1
Metronidazole S
Quinupristin dalfoppristin I
Linezolid I
Colistimethate X1

Disposition

  • Admit:
    • Severe diarrhea
    • Outpatient antibiotic failure
    • Systemic response (fever, leukocytosis, severe abdominal pain)

See Also

References

  1. ↑ Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
  2. ↑ 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.
  3. ↑ Clostridium difficile Infection in children. Sammons JS, Toltzis P, Zaoutis TE. JAMA Pediatr. 2013 Jun; 167(6):567-73.
  4. ↑ Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
  5. ↑ Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
  6. ↑ IDSA Guidelines PDF
  7. ↑ 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/
  8. ↑ Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157
  9. ↑ Louie TJ et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.
  10. ↑ 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.
  11. ↑ Sanford Guide to Antimicrobial Therapy 2014
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