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Meningococcemia, Emergency Medicine

Basics

Description

- "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

- 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)

- Meningitis may or may not be present. - Waterhouse " Friderichsen syndrome: - Bilateral hemorrhagic destruction of adrenal glands - Vasomotor collapse

- 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

- 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)

  • 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 W135Serotype B is most common in USMajority 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 rateAge 20 " 40 yr: 30 " 40% carrier rateLower 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 commonPreceded by upper respiratory infectionFever, chills, myalgias/arthralgias, malaiseOften self-limited, resolving in several daysCan progress to meningitis (mortality rate 2 " 10%) or overwhelming sepsis without meningitis
  • Overwhelming meningococcal sepsis:10% of overall meningococcemia casesHigh mortality rate (20 " 60%)Most deaths occur in 1st 48 hrSudden onset of illness and rapid progression of clinical courseInitial presentation may be mild:Mild tachycardiaMild tachypnea/respiratory symptomsMild hypotensionFever, chills, vomiting, headache, rash, muscle tendernessToxic appearingInfants: Lethargy, poor feeding, bulging fontanelRash:Combination of purpura/ecchymosisMay later exhibit coalescence, necrosis/sloughing of the involved skin (purpura fulminans)Petechiae (over skin, mucous membranes, conjunctivae) seen in 50 " 60%MaculesPapules (scrapings of papules demonstrate the organism on Gram stain)Deteriorate quickly over several hours:Hypotension/shockAcidosisAcute respiratory distress syndrome (ARDS)Disseminated intravascular coagulation (DIC)Meningitis may or may not be present.Waterhouse " Friderichsen syndrome:Bilateral hemorrhagic destruction of adrenal glandsVasomotor collapseAcute renal failure:From prolonged hypotension (low renal perfusion causing acute tubular necrosis)
  • Chronic meningococcemia:UncommonWell appearingRecurrent fevers, chills, arthralgias over weeks to monthsIntermittent rash " painful on the extremitiesMigratory polyarthritisSplenomegaly (20%)Meningococcal meningitis:HeadacheFeverNeck stiffnessConfusionLethargyObtundation
  • Septic arthritis:Occurs during active meningococcemiaMultiple joints involvedJoint pain, redness, swelling, effusion, fever, chillsExtremely limited or no range of motion
  • Other meningococcal infections:Occur with meningococcal infection elsewhereConjunctivitis " may occur aloneSinusitisPanophthalmitisUrethritisSalpingitisProstatitisPneumoniaMyocarditis/pericarditis:Occurs late in onsetUsually 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 scrapingsGram stain: Intracellular or extracellular gram-negative diplococci

Diagnosis Tests & Interpretation

Lab

  • CBC:Elevated WBCs initially; later may be suppressed in severe diseaseDecreased platelet count when large areas of purpura/petechiae or DIC
  • Electrolytes, BUN, creatinine, glucose
  • CSF:Gram stain, culture, protein and glucose, cell count with differentialConsistent 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 meningococcemiaPositive 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, CHFBegin 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: Ampicillin3rd 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 observationSerogroup-specific vaccine as adjunct only
  • Vaccine:Vaccine recommended in military recruits, travelers to endemic areas, complement-deficient or asplenic patients, 1st-year college dormitory residentsVaccine 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 yr250 mg IM for age >15 yrCiprofloxacin: 500 mg PO (adults)Rifampin: 600 mg (peds: 5 " 10 mg/kg) PO BID for 2 daysAzithromycin 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.

See Also (Topic, Algorithm, Electronic Media Element)

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)