Meningococcemia- Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • Caused by Neisseria meningitidis in the blood, which results in a broad spectrum of clinical manifestations
  • Bacteremia without sepsis: Patient has upper respiratory symptoms only and recovers spontaneously without antibiotic.
  • Bacteremia without meningitis: Patient is acutely ill, and may have skin manifestations (rashes, petechiae, and ecchymosis) and hypotension.
  • Bacteremia with meningitis:
    • Predominant clinical picture of meningitis: Headache, decreased sensorium, and neck rigidity
    • Skin manifestations and hypotension may also be present.
  • Bacteremia with acute arthritis dermatitis syndrome: Patient may have tenosynovitis typical of gonococcal etiology.

Epidemiology

Incidence

  • 0.3–1.0/100,000 in the US (2,500–3,500 cases annually)
  • Incidence during epidemics in sub-Saharan Africa can be as high as 2%.

Risk Factors

  • Age: 3 months–1 year
  • Late complement component deficiency (C5, C6, C7, C8, or C9)
  • Household contacts
  • Contacts in nurseries and day care centers
  • Close quarters (e.g., dormitories, campus bars, and military barracks)

Genetics

Late complement component deficiency has an autosomal recessive inheritance.

General Prevention

  • Quadrivalent meningococcal polysaccharide-protein conjugate vaccine (MCV4) is available.
  • Vaccine is recommended for all persons 11–18 and persons 19–55 at increased risk for the disease:
    • Guillain-Barré syndrome has been associated with the MCV4 vaccine, so personal history of Guillain-Barré is a relative contraindication for receiving this vaccine (1)[A],(2)[B].
  • Vaccine is required by the Government of Saudi Arabia for Hajj pilgrims above age 2 and is also recommended by the CDC for this group of travelers.
  • CDC also advises vaccination for travelers to sub-Saharan Africa (meningitis belt) during dry season.

Etiology

  • Neisseria meningitidis, a gram-negative diplococcus with at least 13 serotypes
  • Major serogroups in the US: B, C, Y, and W-135:
    • Serogroup B is predominant cause of meningococcemia in children <1 year of age.
    • Serogroup C is the most common cause in the US.
  • Major serogroups worldwide are B, C, and W-135:
    • W-135 is the major cause of disease in the “meningitis belt” of sub-Saharan Africa.

Neisseria meningitidis, Blood culture, autosomal recessive inheritance, upper respiratory symptoms, skin manifestations, acute arthritis,

Diagnosis

History

  • Symptoms:
    • Fever, headache, chills, rigor, sore throat
    • Changes in mental status, stiff neck, convulsions
    • Arthralgias, arthritis
  • Be sure to ask about possible exposures: Living in barracks, dormitories, and travel to endemic regions, especially sub-Saharan Africa

Physical Exam

  • Look for skin findings: Maculopapular rash, petechiae, ecchymosis, purpura.
  • Stiff neck, focal neurologic signs, coma
  • Hypotension, shock

Diagnostic Tests & Interpretation

Alert

  • When meningococcemia is suspected, treatment should never be delayed for diagnostic tests.
  • Antibiotic administration may render blood and/or CSF culture negative within 2 hours, so begin treatment and then test.

Lab

Initial lab tests

  • Leukocytosis or leukopenia
  • Left shift of leukocytes, toxic granulation
  • Thrombocytopenia
  • Lactic acidosis
  • Prolonged PT/PTT
  • Low fibrinogen
  • Elevated fibrin degradation products
  • Blood culture growing N. meningitidis
  • Cerebrospinal fluid:
    • Cloudy
    • Increased white blood cells with polymorphonuclear cells predominant
    • Gram stain showing gram-negative diplococci
    • Glucose-to-blood glucose ratio <0.4
    • Protein >45 mg/dL
    • Positive for N. meningitidis antigen (MAT or PCR)
    • Culture positive for N. meningitidis

Imaging

Initial approach

CT scan of head if concern for space-occupying lesions

Diagnostic Procedures/Surgery

  • Blood culture
  • Lumbar puncture:
    • After a brief history and physical exam suggest meningitis, initiate antibiotics and then proceed with lumbar puncture within 1 hour.

Pathological Findings

  • Disseminated intravascular coagulation
  • Exudates on meninges
  • Polymorphonuclear infiltration of meninges
  • Hemorrhage of adrenal glands

Differential Diagnosis

  • Septicemia due to other microorganism
  • Meningitis due to other pyogenic bacteria
  • Gonococcemia
  • Acute bacterial endocarditis
  • Rocky Mountain spotted fever
  • Hemolytic uremic syndrome
  • Gonococcal arthritis dermatitis syndrome
  • Influenza

Treatment

Medication

First Line

  • In patients strongly suspected of having meningitis, consider administering dexamethasone 0.15 mg/kg q6h for 16 doses, starting 15 minutes before 1st dose of antibiotic:
    • Corticosteroids are likely less effective in cases of meningococcal meningitis and patients with HIV (3)[B].
    • Use of corticosteroids lowers mortality in adults but may not improve outcomes in pediatric patients.
  • Treatment for suspected meningococcal meningitis must begin as soon as possible; coverage for other possible causes of meningitis must be given until a definitive diagnosis is made.
  • Age influences etiologic organism.
  • Age <4 weeks: Ampicillin plus cefotaxime or ceftriaxone
  • Age 4–12 weeks: Ampicillin plus cefotaxime or Ceftriaxone plus Vancomycin
  • Age 12 weeks to adulthood: Cefotaxime or ceftriaxone plus vancomycin
  • When treating an adult patient with suspected meningitis, initiate early therapy as above. Once N. meningitidis is identified, the drug of choice remains penicillin (4)[C].
  • For meningitis:
    • Penicillin G 4 million units IV q4h (pediatric dose: 0.25 mU/kg IV q4–6h) or ampicillin2 g IV q4h (pediatric dose: 200–300 mg/kg IV q6h)
    • Use alternate drugs if patient is allergic to penicillin.
  • For other infections: Use 1/2 the dose for meningitis.
  • Duration of treatment: 7–10 days
  • Chemoprophylaxis for close contacts (household members and personnel in nurseries, day care centers, nursing homes, dormitories, and other closed institutions) and vaccination of household contacts (if case is a vaccine preventable serogroup) (5)[A]. No chemoprophylaxis is needed for casual contacts, health care personnel (except persons giving mouth-to-mouth resuscitation), schoolmates, and office co-workers:
    • Rifampin 600 mg (pediatric dose: 10 mg/kg) PO q12h for 2 days or (for adults only) 1 dose of ciprofloxacin 750 mg PO (6)[B]
  • Precautions:
    • Adjust dosage of both medications in patients with severe renal dysfunction.
    • Rifampin ingestion causes orange urine.

Second Line

  • For meningitis:
    • Chloramphenicol 1 g IV q6h (pediatric dose: 75–100 mg/kg q6h) or ceftriaxone 2 g IV q12h (pediatric dose: 80–100 mg/kg q12–24h)
    • In large outbreaks, a single dose of long-acting chloramphenicol has been used. Single-dose ceftriaxone shows equal efficacy in 1 RCT [B].
  • Precautions:
    • Ceftriaxone should not be used in patients with history of anaphylactic reactions to penicillin (e.g., hypotension, laryngeal edema, wheezing, hives).
    • Chloramphenicol may cause aplastic anemia.
  • For other infections:
    • Ceftriaxone 1 g (pediatric dose: 40 mg/kg) IV q24h

Additional Treatment

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General Measures

  • Appropriate antibiotic
  • Supportive care:
    • IV fluids
    • Oxygen when needed
  • Close monitoring of patient for seizure activity

Issues for Referral

Potential complications:

  • Disseminated intravascular coagulation (DIC)
  • Acute respiratory distress syndrome
  • Renal failure
  • Adrenal failure

In-Patient Considerations

Initial Stabilization

  • If meningitis suspected, initiate antibiotics and then proceed to immediate lumbar puncture.
  • Droplet isolation for 24 hours from the beginning of antibiotic therapy

Admission Criteria

Admit patient to ICU if severe sepsis or meningitis is suspected.

IV Fluids

  • Replace volume as needed.
  • Patient may present with septic shock and will require resuscitation with large volumes of crystalloid.

Ongoing Care

Follow-Up Recommendations

  • Before discharge, to eradicate carriage, give patient a prescription for rifampin 600 mg (children 10 mg/kg) PO q12h for 2 days or, for adults only, 1 dose of ciprofloxacin 500–750 mg PO (6)[B].
  • In patients with neurologic deficits, follow-up with a neurologist may be needed.

Diet

As tolerated, depending on clinical condition

Patient Education

  • Educate family and close contacts regarding risk of contracting meningococcal infections.
  • Educate healthcare personnel who are not at risk of contracting meningococcal infections.

Prognosis

Overall mortality 10%

Complications

  • DIC
  • Acute tubular necrosis
  • Seizures
  • Focal neurologic deficit
  • Cranial nerve palsies
  • Sensorineural hearing loss
  • Obstructive hydrocephalus
  • Subdural effusions
  • Acute adrenal hemorrhage
  • Waterhouse-Friderichsen syndrome

References

1. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices. Revised recommendations of the Advisory Committee on Immunization Practices to Vaccinate all Persons Aged 11–18 Years with Meningococcal Conjugate Vaccine. MMWR Morb Mortal Wkly Rep. 2007;56:794–5.

2. Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine–United States, June 2005–September 2006. MMWR Morb Mortal Wkly Rep. 2006;55:1120–4.

3. Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med. 2007;357:2441–50.

4. Sinner SW, Tunkel AR. Antimicrobial agents in the treatment of bacterial meningitis. Infect Dis Clin North Am. 2004;18:581–602, ix.

5. Hoek MR, Christensen H, Hellenbrand W, et al. Effectiveness of vaccinating household contacts in addition to chemoprophylaxis after a case of meningococcal disease: a systematic review. Epidemiol Infect. 2008;1–7.

6. Fraser A, Gafter-Gvili A, Paul M, et al. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2005;CD004785.

Additional Reading

Recommended Immunization Schedules for Persons Aged 0 Through 18 Years – United Stated, 2010 January 8, 2010;58(51–52):1–4.

Codes

ICD9

  • 036.0 Meningococcal meningitis
  • 036.2 Meningococcemia

Snomed

  • 4089001 Meningococcemia (disorder)
  • 192644005 meningococcal meningitis (disorder)

Clinical Pearls

  • Chemoprophylaxis is needed for close contacts.
  • Penicillin and cephalosporins alone will not eradicate carrier status; additional treatment with rifampin (for children or adults) or ciprofloxin (for adults only) is required.
  • Prevention with vaccination is key.

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