Updated: 6/1/2018

Corynebacterium diphtheriae

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Snapshot
  • A 4-year-old girl presents to the emergency room for a fever and sore throat. She recently visited Thailand for 2 months with her parents and had just flown back a couple of days ago. Her parents report that she has not had any of her recommended immunizations, as they have traveled all over the world. On physical exam, there is a grayish-white membrane covering her soft palate. When irritated by a tongue depressor, the membrane oozes with blood. She also has marked cervical lymphadenopathy and edema of the neck. She is immediately admitted for monitoring, antibiotics, and antitoxin.
Introduction
  • Classification
    • Corynebacterium diphtheriae
      • aerobic gram-positive rod
      • produces diphtheria toxin
    • transmission
      • respiratory droplets
  • Epidemiology
    • demographics
      • rare in the US
      • more common in developing countries
  • Pathogenesis
    • diphtheria exotoxin inactivates elongation factor (EF-2) via ADP-ribosylation
      • inhibits protein synthesis, causing necrosis in respiratory, cardiac and central nervous system tissue
      • affects mucous membranes, especially the respiratory tract
    • exotoxin is encoded by β-prophage
  • Associated conditions
    • diphtheria
    • cutaneous diphtheria
      • ulcerative lesions or cellulitis can occur independently of respiratory diphtheria
  • Prevention
    • DTap vaccine
      • vaccine against diphtheria, tetanus, and pertussis
      • 5 doses before school-age, completed by 4-6 years of age
    • Tdap vaccine
      • booster vaccine at 11-12 years of age
      • should also be given to pregnant mothers and those around them
    • Td vaccine
      • tetanus and diphtheria toxoid vaccine at 10-year intervals
  • Prognosis
    • symptoms are insidious
    • mortality is higher in young children, but generally good with prompt treatment
Presentation
  • Symptoms
    • fever
    • sore throat
    • malaise
    • may have a croup-like cough
  • Physical exam
    • pseudomembranous pharyngitis
      • gray or bluish white membrane seen on soft palate, tonsils, or back of the throat
      • bleeds easily if irritated
      • develops 2-3 days after symptoms
    • severe cervical lymphadenopathy
      • “bull neck”
    • myocarditis
    • arrhythmias
Studies
  • Bacterial culture
    • gram-positive rods with blue and red granules (metachromically) seen on culture
      • cysteine-tellurite agar (appears as black colonies)
      • Löffler medium
    • positive Elek test for diphtheria toxin
  • Making the diagnosis
    • most cases are clinically diagnosed and confirmed with a culture
Differential
  • Streptococcal pharyngitis
    • distinguishing factor
      • no pseudomembrane on mucous membranes
Treatment
  • Medical
    • diphtheria antitoxin
      • indication
        • all patients
    • antibiotics
      • indications
        • all patients
      • drugs
        • erythromycin
        • penicillin G
Complications
  • Airway compromise from soft tissue swelling
  • Heart failure from myocarditis
  • Secondary bacterial infection (e.g., pneumonia)
 

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Questions (5)
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.1) A 12-year-old male whose family recently emigrated from eastern Europe presents to the emergency room with a fever of 103.5F, a swollen neck (Figure A), difficulty breathing, and grayish-white membranes in the oropharynx (Figure B). Cultures were taken from the pharynx and the bacteria were found to be Gram-positive rods with metachromatic granules (Figure C). The toxin produced by this bacterium has which of the following mechanism of action? Review Topic

QID: 106293
FIGURES:
1

Pertussis toxin inhibits the G-protein Gi alpha subunit via ADP ribosylation

5%

(1/20)

2

Overactivates guanylate cyclase

5%

(1/20)

3

Inactivates the 60S ribosomal subunit

0%

(0/20)

4

Inactivates elongation factor 2

75%

(15/20)

5

Cleaves SNARE proteins

10%

(2/20)

M1

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SUBMIT RESPONSE 4

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(M1.MC.71) A 6-year-old male who recently immigrated to the United States from Asia is admitted to the hospital with dyspnea. Physical exam reveals a gray pseudomembrane in the patient's oropharynx along with lymphadenopathy. The patient develops myocarditis and expires on hospital day 5. Which of the following would have prevented this patient's presentation and decline? Review Topic

QID: 101530
1

Increased CD4+ T cell count

0%

(0/19)

2

Secretory IgA against viral proteins

11%

(2/19)

3

Increased IgM preventing bacterial invasion

11%

(2/19)

4

Circulating IgG against AB exotoxin

79%

(15/19)

5

Improved IgE release from mast cells

0%

(0/19)

M1

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SUBMIT RESPONSE 4

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(M1.MC.175) A 3-year-old male is brought to the ER with a sore throat and fever. Examination of the pharynx reveals a dark, inflammatory exudate. Cysteine-tellurite agar culture produces black, iridescent colonies. Microscopic features of the causal organism most likely include which of the following? Review Topic

QID: 101634
1

Serpentine growth patterns

11%

(16/142)

2

Metachromic granules

24%

(34/142)

3

Lancet-shape

19%

(27/142)

4

Long, branching filaments

20%

(29/142)

5

Kidney-bean shaped rod

11%

(16/142)

M1

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SUBMIT RESPONSE 2
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