Updated: 1/19/2019

Neisseria meningitidis

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  • An 18-year-old man presents to the emergency department for an intractable headache and generalized malaise. His symptoms began 3 days ago and have progressively worsened. Physical examination is significant for nuchal rigidity, diffuse petechia, and an inability to extend at the knee while the hips are flexed at 90°. A lumbar puncture is performed and cerebral spinal fluid studies demonstrate an elevated opening pressure, elevated protein, decreased glucose, and a leukocytosis. Gram stain of the cerebral spinal fluid demonstrates gram-negative diplococci.
Introduction
  • Classification
    • a gram-negative diplococcus
  • Epidemiology
    • risk factors 
      • college students
      • military
      • infants and the elderly
      • no meningococcus vaccine
  • Transmission
    • respiratory and oral secretions
  • Microbiology
    • properties
      • metabolizes glucose
      • produces IgA proteases
      • contains lipooligosaccharides (has strong endotoxin activity)
      • aerobic or facultatively anaerobic
      • maltose fermenter 
    • reservoir
      • nasopharynx
        • penetrates mucosal epithelium and enters circulation
          • pharynx → hematogenous spread (blood) → choroid plexus → meninges 
    • molecular biology
      • virulence factors
        • polysaccharide capsule 
          • an important virulence factor
            • provides resistance against phagocytosis
        • IgA protease
          • allows oropharynx colonization
        • endotoxin (lipooligosaccharide)
          • analogous to LPS from other gram-negative bacteria
          • causes hemorrhage and sepsis
          • responsible for petechial rash
            • small red dots of hemorrhage
        • pili
          • enables attachment to the nasopharynx 
          • antigenic variation avoids the immune system attack
  • Pathogenesis
    • begins as asymptomatic colonization in the nasopharynx in healthy patients
      • in rare cases, the bacteria invade through the mucosa, resulting in bacteremia, which can allow seeding of the microbe to the meninges
      • an inflammatory response against the microbe (due to its endotoxin) ensues, leading to tissue injury
        • procoagulant pathways can also be activated, causing intravascular thrombosis (e.g., purpura and petechiae)
  • Prevention
    • meningococcal vaccine
      • indication
        • all patients 11-18 years of age
        • ≤ 10 years of age and ≥ 19 years of age who are high risk for invasive meningococcal disease
  • Associated conditions
    • meningitis
    • meningococcemia
    • purpural fulminans
    • Waterhouse-Friderichsen syndrome  
      • adrenal infarction leading to adrenal insufficiency 
  • Prognosis
    • poor prognosis include shock, young and old age, coma, purpura fulminans, and disseminated intravascular coagulation
Presentation
  • Symptoms
    • headache
    • fever
    • neck stiffness
    • nausea and vomiting
    • myalgias
  • Physical
    • petechial rash 
    • nuchal rigidity
    • Brudzinki sign
      • spontaneous flexion of the hips during passive neck flexion
    • Kernig sign
      • inability to extend the knees while the hips are flexed at 90°
Studies
  • Culture
    • perform a Gram stain of the cerebral spinal fluid or blood
      • gold standard for the diagnosis
Differential
  • Meningitis caused by other organisms
    • Streptococcus pneumoniae
    • Listeria monocytogenes
    • differentiating factors
      • different organisms are isolated with microbiologic testing
Treatment
  • Medical
    • empiric antibiotic therapy
      • indication
        • preferably given after cerebral spinal fluid cultures and blood cultures are obtained
          • given antibiotics first will impair diagnostic testing
      • regimen
        • third-generation cephalosporin
          • e.g., ceftriaxone or cefotaxime 
    • antimicrobial chemoprophylaxis
      • indication
        • ideally given within 24 hours
          • household members
          • roommates or intimate contacts
          • direct exposure to oral or respiratory secretions (e.g., kissing and endotracheal intubation)
          • sitting next to the infectious person for ≥ 8 hours
          • patients who work in a childcare center
      • medication
        • rifampin
        • ciprofloxacin
        • ceftriaxone
Complications
  • Sepsis
  • Hypovolemic shock
  • Cerebral edema and hydrocephalus
  • Cognitive impairment
 

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Questions (8)
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.4798) A 22-year-old female is brought to the emergency department by her roommate with a one day history of fever and malaise. She did not feel well after class the previous night and has been in her room since then. She has not been eating or drinking due to severe nausea. Her roommate checked on her one hour ago and was alarmed to find a fever of 102°F (38.9°C). On physical exam temperature is 103°F (40°C), blood pressure is 110/66 mmHg, pulse is 110/min, respirations are 23/min, and pulse oximetry is 98% on room air. She refuses to move her neck and has a rash on her trunk. You perform a lumbar puncture and the CSF analysis is shown below.

Appearance: Cloudy
Opening pressure: 180 mm H2O
WBC count: 150 cells/µL (93% PMN)
Glucose level: < 40 mg/dL
Protein level: 50 mg/dL
Gram stain: gram-negative diplococci

Based on this patient's clinical presentation, which of the following should most likely be administered? Review Topic

QID: 109200
1

Ceftriaxone

85%

(90/106)

2

Rifampin

3%

(3/106)

3

Erythromycin

8%

(8/106)

4

Acyclovir

2%

(2/106)

5

Dexamethasone

2%

(2/106)

M1

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PREFERRED RESPONSE 1

(M1.MC.75) A 19-year-old college student is brought to the emergency department by her roommate. Her roommate reports that the patient was complaining of a headache this morning. A few hours later, the patient seemed lethargic and confused. In the emergency department, the patient's vital signs are as follows: HR 98, BP 110/70, T 38.7 degrees Celsius. Her neurological exam is notable for flexion at the hips when her neck is passively flexed. A lumbar puncture is performed, and Gram stain results are shown in Figure A. Which of the following bacterial structures does the involved organism use to adhere to the nasopharynx? Review Topic

QID: 106716
FIGURES:
1

Lipooligosaccharide

7%

(1/15)

2

Pilus

60%

(9/15)

3

Capsule

13%

(2/15)

4

Spore

7%

(1/15)

5

Glycocalyx

13%

(2/15)

M1

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PREFERRED RESPONSE 2

(M1.MC.1) An 18-year-old male in his first year of college presents to the emergency room with a fever and a severe headache. He reports having unprotected sex with several partners over the past few weeks. Upon examination, the male demonstrates nuchal rigidity and photophobia. His past medical history is notable for a lack of vaccinations beginning from infancy due to his parents' belief that vaccinations may cause autism. The bacteria causing these symptoms would most likely demonstrate which of the following? Review Topic

QID: 106341
1

Positive quellung reaction

60%

(6/10)

2

Negative quellung reaction

0%

(0/10)

3

Lactose fermentation

0%

(0/10)

4

Urease positive

10%

(1/10)

5

Negative catalase test

30%

(3/10)

M1

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PREFERRED RESPONSE 1

(M1.MC.21) A 15-year-old female is brought to the emergency room with high fever and confusion. She complains of chills and myalgias, and physical examination reveals a petechial rash. Petechial biopsy reveals a Gram-negative diplococcus. The patient is at greatest risk for which of the following? Review Topic

QID: 101480
1

Bilateral adrenal destruction

57%

(12/21)

2

Pelvic inflammatory disease

5%

(1/21)

3

Septic arthritis

19%

(4/21)

4

Osteomyelitis

10%

(2/21)

5

Acute endocarditis

10%

(2/21)

M1

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PREFERRED RESPONSE 1
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(M1.MC.173) A 19-year-old man is admitted to the medical intensive care unit with suspected sepsis. Blood cultures grow Gram-negative cocci containing lipooligosaccharide in their cell wall. Which of the following would you expect to find on a detailed history and physical examination of this patient? Review Topic

QID: 101632
1

History of consuming undercooked beef

16%

(3/19)

2

Petechial rash

68%

(13/19)

3

Ascending paralysis

11%

(2/19)

4

History of exposure to rabbit hides

5%

(1/19)

5

Rice water stools

0%

(0/19)

M1

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PREFERRED RESPONSE 2
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