Clostridium difficile

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
    • ~40% of infants < 1 month are colonized and asymptomatic[3]
    • ~15% in infants 6-12 months
    • By 2 years of age, normal flora is established, similar to adults[4]
  • 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

Noninfectious

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)
  • 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[6]

Mild

  • Either discontinue offending antibiotics(if possible) or give Metronidazole 500mg PO q6hr x10-14d

Moderate

Severe

Criteria:[7][8]

  • 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 125-250mg PO q6hr x10d (IV form is not effective)
  • Add Metronidazole 500mg IV q6hr if ileus or patient cannot tolerate PO
  • 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:
    • IVIG
    • Fecal transplant
    • Fidamoxicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 wks after treatment (~15% vs 25%) [10]

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]

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