Meningococcemia, Emergency Medicine

Basics

Description

Bacterial illness caused by Neisseria meningitidis
Several forms of illness may occur
Mild meningococcemia
Overwhelming meningococcal sepsis
Meningococcal meningitis
Chronic/occult meningococcemia
Septic arthritis
Acquired from close contact with an infected individual or an asymptomatic carrier
Intimate kissing and cigarette smoking are independent risk factors.

Etiology

N. meningitidis:
- Serotypes A, B, C, D, H, I, K, L, X, Y, Z, 29E, and W135
- Serotype B is most common in US
- Majority of infections caused by A, B, C, X, Y, and W135
Bacteria attach to and enter nasopharyngeal epithelial cells.
Bacteria spread from the nasopharynx through the bloodstream via entry of vascular endothelium.
Most circulating meningococci are eliminated by the spleen.
Meningococci produce an endotoxin (lipooligosaccharide):
- Involved in pathogenesis of the skin, adrenal manifestations, and vascular collapse
Human oropharynx/nasopharynx is the only reservoir.
Carrier usually has developed immunity to serotype-specific antibody (not immune to all serotypes):
- Age <5 yr: 1% carrier rate
- Age 20 " 40 yr: 30 " 40% carrier rate
- Lower rate of immunity in children, which is reflected by the higher rates of infection
Most common in fall and spring
Increased incidence in military recruits and close living conditions
Epidemics " ages 5 " 9 yr most/earliest affected

Diagnosis

Signs and Symptoms

"Mild " meningococcemia:
- Most common
- Preceded by upper respiratory infection
- Fever, chills, myalgias/arthralgias, malaise
- Often self-limited, resolving in several days
- Can progress to meningitis (mortality rate 2 " 10%) or overwhelming sepsis without meningitis
Overwhelming meningococcal sepsis:
- 10% of overall meningococcemia cases
- High mortality rate (20 " 60%)
- Most deaths occur in 1st 48 hr
- Sudden onset of illness and rapid progression of clinical course
- Initial presentation may be mild:
  - Mild tachycardia
  - Mild tachypnea/respiratory symptoms
  - Mild hypotension
- Fever, chills, vomiting, headache, rash, muscle tenderness
- Toxic appearing
- Infants: Lethargy, poor feeding, bulging fontanel
- Rash:
  - Combination of purpura/ecchymosis
  - May later exhibit coalescence, necrosis/sloughing of the involved skin (purpura fulminans)
  - Petechiae (over skin, mucous membranes, conjunctivae) seen in 50 " 60%
  - Macules
  - Papules (scrapings of papules demonstrate the organism on Gram stain)
- Deteriorate quickly over several hours:
  - Hypotension/shock
  - Acidosis
  - Acute respiratory distress syndrome (ARDS)
  - Disseminated intravascular coagulation (DIC)
- Meningitis may or may not be present.
- Waterhouse " Friderichsen syndrome:
  - Bilateral hemorrhagic destruction of adrenal glands
  - Vasomotor collapse
- Acute renal failure:
  - From prolonged hypotension (low renal perfusion causing acute tubular necrosis)
Chronic meningococcemia:
- Uncommon
- Well appearing
- Recurrent fevers, chills, arthralgias over weeks to months
- Intermittent rash " painful on the extremities
- Migratory polyarthritis
- Splenomegaly (20%)
- Meningococcal meningitis:
- Headache
- Fever
- Neck stiffness
- Confusion
- Lethargy
- Obtundation
Septic arthritis:
- Occurs during active meningococcemia
- Multiple joints involved
- Joint pain, redness, swelling, effusion, fever, chills
- Extremely limited or no range of motion
Other meningococcal infections:
- Occur with meningococcal infection elsewhere
- Conjunctivitis " may occur alone
- Sinusitis
- Panophthalmitis
- Urethritis
- Salpingitis
- Prostatitis
- Pneumonia
- Myocarditis/pericarditis:
  - Occurs late in onset
  - Usually associated with serogroup C

History
Progression of illness is variable and classifies illness into mild, overwhelming, and chronic.
Physical Exam

Tachycardia
Hypotension, which may be mild initially
Progressive, rapid deterioration
Respiratory failure with ARDS picture
Petechial rash 50 " 80%:
- Involves axillae, flanks, wrists, ankles

Essential Workup

Do not allow workup (including delay in lumbar puncture) to postpone resuscitation and administration of antibiotics in suspected cases of meningococcemia.
Suspect diagnosis in setting of dramatic clinical presentation.
Gram stain and culture of:
- Peripheral blood, CSF, sputum, urine, joint aspirate, or petechial/papular scrapings
- Gram stain: Intracellular or extracellular gram-negative diplococci

Diagnosis Tests & Interpretation

Lab

CBC:
- Elevated WBCs initially; later may be suppressed in severe disease
- Decreased platelet count when large areas of purpura/petechiae or DIC
Electrolytes, BUN, creatinine, glucose
CSF:
- Gram stain, culture, protein and glucose, cell count with differential
- Consistent with bacterial infection in meningococcal meningitis
Arterial blood gases for acidosis, hypoxia
Fibrinogen levels, fibrin degradation products, prothrombin time, partial thromboplastin time if DIC suspected
Throat/nasopharyngeal swab:
- Positive swab does not establish the diagnosis of meningococcemia.
Analysis of buffy-coat layer of peripheral blood for bacteria if sepsis is suspected
Blood culture:
- Often negative with chronic meningococcemia
- Positive in mild and overwhelming meningococcemia
Immunoassays (beware false negatives)
Polymerase chain reaction, especially useful when antibiotics given before specimen collection

Imaging
CXR: For ARDS/pneumonia
Diagnostic Procedures/Surgery
Amputations and debridement of necrotic tissue and/or extremities may be necessary.

Differential Diagnosis

Viral exanthem
Vasculitis
Mycoplasma
Rocky Mountain spotted fever
Toxic shock syndrome
Henoch " Sch Άnlein purpura
Idiopathic thrombocytopenic purpura
Dengue fever
Disseminated gonococcal infection
Influenza
Streptococcus group A and B
Thrombotic thrombocytopenic purpura

Treatment

Pre-Hospital

Postexposure prophylaxis needed for pre-hospital personnel in close contact with patient

Initial Stabilization/Therapy

Wear mask and gloves, observe droplet precautions.
Notify department of health.
ABCs
Immediate endotracheal intubation for severe acidosis, hypoxia, or decreased mental status:
- Hyperventilate to treat acidosis (target PCO2 about 25 mm Hg)
Treat hypotension:
- 0.9% normal saline bolus of 20 mL/kg; cautious rehydration with ARDS, CHF
- Begin dopamine or norepinephrine (epinephrine if no response) if hypotensive after 2 L of IV fluids.
Naloxone, thiamine, dextrose (Accu-Chek) for altered mental status
Initiate IV antibiotics:
- 1st line: High-dose penicillin (proven meningococcemia) or 3rd-generation cephalosporin (broader coverage pending definitive diagnosis)
- 2nd line: Ampicillin
- 3rd line: Chloramphenicol (penicillin-allergic patients)

Ed Treatment/Procedures

Overwhelming meningococcal sepsis
Severe acidosis (pH <7 " 7.1 or serum HCO3 <8 " 10):
- Administer IV NaHCO3 along with hyperventilation.
Insert Foley catheter to monitor urine output.
Place in respiratory isolation.
High-dose steroids:
- To protect against cranial nerve injury in the setting of ongoing infection (controversial)
- Administer with adrenal gland injury.
DIC treatment:
- Administer fresh-frozen plasma and platelet transfusions.
- Heparin is not indicated unless significant thrombotic complications are evident clinically (e.g., cyanosis or cold digits, low urine output despite adequate volume status, and blood pressure).
Prophylaxis options for close contacts:
- Ideally, prophylaxis should be given within 1st 24 hr.
- 10-day window of observation
- Serogroup-specific vaccine as adjunct only
Vaccine:
- Vaccine recommended in military recruits, travelers to endemic areas, complement-deficient or asplenic patients, 1st-year college dormitory residents
- Vaccine recommended routinely for ages 11 " 18 yr

The safety of meningococcal vaccine is unclear in pregnancy.

Medication

First Line

Cefotaxime: 2 g (peds: 50 mg/kg) IV q6h
Ceftriaxone: 2 g (peds: 50 mg/kg) IV q12h
Penicillin G: 4 MU (peds: 250,000 U/kg/24 h) IV q4h

Second Line

Ampicillin: 2 " 3 g (peds: 200 " 400 mg/kg/24 h) IV q6h
Chloramphenicol: 50 " 100 mg/kg/24 h IV q6h (max. 4 g/d)
Prophylaxis:
- Single-dose ceftriaxone:
  - 125 mg IM for age <15 yr
  - 250 mg IM for age >15 yr
- Ciprofloxacin: 500 mg PO (adults)
- Rifampin: 600 mg (peds: 5 " 10 mg/kg) PO BID for 2 days
- Azithromycin 500 mg PO single dose (not routinely used)
Dexamethasone: 0.15 mg/kg IV for pediatric meningitis
Dopamine: 5 " 20 ug/kg/min IV titrate to blood pressure (BP)
Epinephrine: 2 " 10 ug/min IV titrate to BP
Heparin: 3,000 " 5,000 U (peds: 80 U/kg) IV bolus followed by 600 " 1,000 U/h (peds: 18 U/kg/h) IV drip
Hydrocortisone (Solu-Cortef): 100 mg (peds: 2 mg/kg) bolus IV for adrenal insufficiency q8h
Meningococcal polysaccharide 0.5 mL IM 1
Meningococcal vaccine 0.5 mL SC 1
Norepinephrine: 0.5 " 30 ug/min IV titrate to BP
Sodium bicarbonate: 2 " 5 mEq/kg (peds: 0.5 " 1 mEq/kg) IV over 30 min to 4 hr

Follow-Up

Disposition

Admission Criteria

ICU admission for overwhelming sepsis with respiratory isolation
Respiratory isolation admission for mild meningococcemia

Discharge Criteria
Prophylaxis for close patient contacts
Issues for Referral

Consider transfer to tertiary care center, as multisystem organ failure is common.
Late neurologic, cardiovascular, and orthopedic complications may necessitate follow-up with specialists.

Follow-Up Recommendations

Complete antibiotic course.
Respiratory precautions may be discontinued after 24 hr.
All close contacts need prophylaxis.

Pearls and Pitfalls

Notify department of health in any suspected case.
Watch for late development of pericardial tamponade.
Do not wait to give antibiotics.

Additional Reading

Apicella M. Neisseria meningitidis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease. 7th ed. Philadelphia, PA: Churchill Livingston Elsevier; 2010:2737 " 2752.
Cramer JP, Wilder-Smith A. Meningococcal disease in travelers: Update on vaccine options. Curr Opin Infect Dis. 2012;25(5):507 " 517.
Pace D, Pollard AJ. Meningococcal disease: Clinical presentation and sequelae. Vaccine. 2012;30(suppl 2):B3 " B9.
Rosenstein R, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med. 2001;344(18):1378 " 1388.

Codes

ICD9

036.2 Meningococcemia

ICD10

A39.2 Acute meningococcemia
A39.3 Chronic meningococcemia
A39.4 Meningococcemia, unspecified

SNOMED

4089001 Meningococcemia (disorder)
186365005 Acute meningococcemia
240426001 chronic meningococcemia (disorder)

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