Updated: 11/3/2018

Clostridium difficile

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Snapshot
  • An 89-year-old man with a past medical history of gastritis presents to the hospital for dehydration and watery diarrhea. He started having diarrhea and some weakness about 2 days ago and had not been able to keep up with his fluid intake. He has been taking omeprazole for over 30 years and was recently treated with clindamycin for a soft tissue infection. On laboratory evaluation, he has a marked leukocytosis. He is started on oral vancomycin.  
Introduction
  • Classification
    • Clostridium difficile
      • anaerobic, gram + rod
      • produces 2 toxins that bind to intestinal mucosal cells
      • forms heat-resistant spores
  • Epidemiology
    • incidence
      • common
    • risk factors
      • recent antibiotics use
        • clindamycin
        • ampicillin
        • cephalosporins
        • fluoroquinolones
      • proton-pump inhibitors
      • recent hospitalization
      • advanced age
  • Pathogenesis
    • causes a pseudomembranous colitis and diarrhea  
      • characterized by yellow-white plaques in intestinal mucosa
      • pseudomembranous plaques are made from fibrin
    • toxin A is an enterotoxin that binds to the intestinal brush border
    • toxin B is a cytotoxin and depolymerizes actin, disrupting the cytoskeleton
  • Prognosis
    • relapse occurs in ~20% of patients
Presentation
  • Symptoms
    • crampy abdominal pain
    • anorexia
    • malaise
    • diarrhea
      • typically watery diarrhea
      • occasionally may be bloody but without frank blood
  • Physical exam
    • fever
    • dehydration
    • abdominal tenderness to palpation
    • rebound tenderness in severe cases
Imaging
  • Abdominal radiography
    • indications
      • if toxic megacolon is suspected
      • for quick diagnosis and assess for early intervention
    • findings
      • dilated colon
  • Abdominal computed tomography (CT)
    • indication
      • suspicion for pseudomembranous colitis
    • findings
      • marked thickening of the colonic wall (accordion sign)
      • irregularity of bowel wall
      • pericolonic stranding
Studies
  • Labs
    • ↑ white blood cells
    • ↓ hypoalbuminemia
    • ↑ lactate
    • diagnostic tests of the stool
      • polymerase chain reaction for the organism
      • detection of antigen
      • + fecal leukocytes
  • Making the diagnosis
    • based on clinical presentation and stool studies
Differential
  • Ulcerative colitis
    • distinguishing factors
      • typically presents with bloody diarrhea
      • can also present with dermatologic manifestations such as erythema nodosum
  • Crohn disease
    • distinguishing factors
      • can be bloody or nonbloody
      • can present with fistulas
      • can also present with dermatologic manifestations such as erythema nodosum
Treatment
  • Management approach
    • 10-day course of antibiotics
  • Medical
    • oral vancomycin
      • indications
        • resistant to metronidazole
        • severe cases
    • fidaxomicin
      • indication
        • recurrent cases
    • oral metronidazole
      • indications
        • used as an alternative if vancomycin or fidaxomicin are not available
        • used in addition to vancomycin if patients are refractory to monotherapy
        • contraindicated in the elderly
    • fecal microbiota transplant
      • indication
        • recurrent cases
Complications
  • Colonic perforation
    • occurs in small percentage of patients
  • Toxic megacolon
    • occurs in small percentage of patients
 

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Questions (7)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MC.29) A 68-year-old alcoholic male who is hospitalized for treatment of a pulmonary abscess with clindamycin develops recurrent foul, watery diarrhea on day 6 of his hospitalization. His condition has otherwise improved, with only a low grade fever and mild abdominal pain. A stool toxin study is sent which successfully diagnoses the cause of his diarrhea. Which of the following histologic images best corresponds to this patient's pathology? Review Topic

QID: 103519
FIGURES:
1

Figure A

8%

(16/198)

2

Figure B

6%

(11/198)

3

Figure C

23%

(45/198)

4

Figure D

53%

(104/198)

5

Figure E

9%

(17/198)

M1

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PREFERRED RESPONSE 4
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(M1.MC.91) An 87-year-old male nursing home resident is currently undergoing antibiotic therapy for the treatment of a decubitus ulcer. One week into the treatment course, he experiences several episodes of watery diarrhea. Subsequent sigmoidoscopy demonstrates the presence of diffuse yellow plaques on the mucosa of the sigmoid colon. Which of the following is the best choice of treatment for this patient? Review Topic

QID: 101550
1

Oral morphine

5%

(1/19)

2

Intravenous gentamicin

5%

(1/19)

3

Oral metronidazole

68%

(13/19)

4

Oral trimethoprim/sulfamethoxazole

0%

(0/19)

5

Intravenous vancomycin

16%

(3/19)

M1

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PREFERRED RESPONSE 3

(M1.MC.7) A 58-year-old man is hospitalized and treated with clindamycin for a pulmonary abscess. During his hospital stay he develops abdominal pain and bloody diarrhea, and has a WBC of 14,000; serum creatinine is 0.9 mg/dL. On teaching rounds, you learn that the responsible pathogen produces a multi-unit toxin that binds to the colonic mucosa, causing actin depolymerization that results in cell death and mucosal necrosis. What is the preferred treatment for this condition? Review Topic

QID: 101466
1

Continue Clindamycin

4%

(13/325)

2

Metronidazole

81%

(262/325)

3

Penicillin G

5%

(15/325)

4

Tetracycline

4%

(12/325)

5

Erythromycin

6%

(19/325)

M1

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PREFERRED RESPONSE 2
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