Topic
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Evidence
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Snapshot
  • A 36-year-old man presents to the emergency department with an altered level of consciousness and fever. He is accompanied by a friend, who says that prior to being altered, he experienced a productive cough, chills, and night sweats. His temperature is 103°F (39.4°C), blood pressure is 70/60 mmHg, pulse is 130/min, and respirations are 14/min. He is immediately started on intravenous fluids, blood cultures are drawn, is started on vancomycin and piperacillin/tazobactam, and is admitted to the medical intensive care unit. In the unit, the patient is stabilized but is still febrile. KOH and calcofluor white are added to fresh wet preparations of the patient's sputum, which demonstrate refractile cell wall, and single, broad-based buds. He is then started on intravenous amphotericin B. (Blastomycosis)
Introduction
  • Mechanism of action
    • binds to ergosterol, which leads to the formation of pores in fungal membranes leaking its internal cellular contents  
  • Mechanism of resistance
    • alterations in ergosterol
  • Clinical use
    • serious (potentially life-threatening) systemic mycoses 
      • aspergillosis
      • cryptococcosis
      • blastomycosis 
      • systemic candidiasis
      • coccidioidomycosis
      • histoplasmosis
      • zygomycosis
      • fungal meningitis
        • medication must be administered intrathecally to target the central nervous system
  • Adverse effects
    • nephrotoxicity
      • hydration decreases the risk
    • intravenous phlebitis
    • anemia
    • cardiac arrhythmia
    • fevers and chills
    • hypokalemia and hypomagnesemia 
      • should supplement these electrolytes in patients in treatment
 

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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 15-year-old year male with a prior history of a kidney transplant presents to his pediatrician complaining of cough, fatigue, and fever after returning from visiting his father for two months in Wisconsin for the spring. He is treated empirically with antibiotics for a possible lower respiratory tract infection. Three weeks goes by and his symptoms do not resolve; he is now experiencing lower back pain and returns to the pediatrician. A spinal tap is performed, and a methenamine silver stained is performed showing a specimen with broad-base budding (Figure A). Which of the following treatments would eliminate the causative agent by binding to ergosterol in the membrane altering the permeability of the membrane? Review Topic

QID: 106423
FIGURES:
1

Clotrimazole

0%

(0/21)

2

Flutocytosine

0%

(0/21)

3

Caspofungin

5%

(1/21)

4

Amphotericin B

90%

(19/21)

5

Fluconazole

5%

(1/21)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M1.MC.5) A 35-year-old African American male is admitted to the hospital following a recent diagnosis of systemic histoplasmosis and subsequently treated with an intravenous anti-fungal agent. During the course of his hospital stay, he complains of headaches. Work-up reveals hypotension, anemia, and elevated BUN and creatinine. His medication is known to cause these side-effects through its binding of cell membrane ergosterol. With which anti-fungal is he most likely being treated? Review Topic

QID: 100808
1

Fluconazole

16%

(45/275)

2

Flucytosine

0%

(1/275)

3

Amphotericin B

78%

(214/275)

4

Terbinafine

1%

(4/275)

5

Griseofulvin

3%

(7/275)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.MC.75) A 45-year-old male seismologist with a 10-year history of AIDS returns from a two-month long stay in Los Angeles three weeks ago and is hospitalized for concurrent pneumonia, meningitis, and vertebral osteomyelitis. A sputum sample was taken and shown to have spherules containing spores (Figure A). Treatment was initiated with a systemic medication that causes fever and chills upon infusion. Which of the following is the mechanism of action of this medication? Review Topic

QID: 106851
FIGURES:
1

Inhibits ergosterol synthesis

14%

(27/187)

2

Binds to ergosterol, forming destructive pores in cell membrane

75%

(140/187)

3

Inhibits squalene epoxidase

6%

(12/187)

4

Inhibits formation of beta glucan

2%

(3/187)

5

Inhibits pyrimidine synthesis

2%

(3/187)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2
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