Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 9/17/2012
Definition 
Meningococcemia is a potentially life-threatening infection of rapid onset, in which bacteremia caused by a encapsulated gram-negative diploccus, Neisseria meningitidis is present.
4 types of conditions occur with Meningococcal infection:
- Meningococcemia: N. meningitidis present circulating in the bloodstream without meningitis (~10% of cases). This will usually present as sepsis without meningitis, with an acutely ill patient with hypotension, and often with skin findings (petechiae, ecchymosis)
- Meningococcal meningitis: Meningitis due to N. meningitidis with no signs of bacteremia (~50% of cases)
- Meningococcal meningitis with bacteremia: Meningitis and bacteremia due to N. meningitidis (~40% of cases). Expect to see signs of meningitis, and also other signs of bacteremia, such as hypotension and skin findings such as petechiae and/or ecchymosis
- Transient bacteremia: Patient with upper respiratory symptoms only, with spontaneous resolution, without intervention or antibiotics (unknown %)
Description
- N. meningitides has 13 serogroups on the basis of capsular polysaccharide antigens. Only 5, A, B, C, W-135, and Y are typical pathogens, causing invasive disease
- N. meningitidis is an opportunistic pathogen colonizing the nasopharynx and oropharnyx of asymptomatic carriers. In some settings, >90% of young adults asymptomatically harbor at least one serogroup. Immunity is common due to exposure through the 3rd decade of life
- An immunization is available which covers for serogroups A, C, W-135 and Y; currently (August 2012), there is no immunization for serogroup B
- 4 types of conditions occur with Meningococcal infection:
- Meningococcemia: N. meningitidis present circulating in the bloodstream without meningitis (~10% of cases). This will usually present as sepsis without meningitis, with an acutely ill patient with hypotension, and often with skin findings (petechiae, ecchymosis)
- Meningococcal meningitis: Meningitis due to N. meningitidis with no signs of bacteremia (~50% of cases)
- Meningococcal meningitis with bacteremia: Meningitis and bacteremia due to N. meningitidis (~40% of cases). Expect to see signs of meningitis, and also other signs of bacteremia, such as hypotension and skin findings such as petechiae and/or ecchymosis
- Transient bacteremia: Patient with upper respiratory symptoms only, with spontaneous resolution, without intervention or antibiotics (unknown %)
- Chronic meningococcemia may be characterized by recurrent episodes of fever, chills, night sweats, headache, migratory arthritis and a maculopapular or petechial rash. This condition is rare and typically escalates over weeks to month until either cultures are taken which show the causative organism, or typical dermatological findings consistent with meningococcemia result in consideration of this diagnosis
Epidemiology
Incidence/Prevalence
- The annual incidence of meningococcal disease varies between approximately 0.5-1.5 cases/100,000 population (US), with some first world countries such as UK and Spain having 4-5/100,000. Sub-Saharan Africa has a history of significant outbreaks where incidence, during outbreaks approaches 500/100,000
- Most infections are sporadic; however reports of local outbreaks, caused predominantly by serogroups B, C and Y have recently been more common in the U.S.
- Group B is most commonly responsible for sporadic outbreaks, whereas, in sub-Saharan African, large epidemics are caused by group A N. meningitidis
- This infection presents most commonly in winter and spring months
- 90% of patients with meningococcal disease have meningococcemia and/or meningitis, only 10% have isolated bacteremia
- Fulminant meningococcemia accounts for 20% of cases
Gender- Males: 1.2 cases per 100,000
- Females: 1 case per 100,000
Age
- Children 5 years of age are most often affected, with peak incidence between 3 and 5 months of age. A second peak occurs between ages 10-25 years
Risk factors
- Children 5 years
- Adolescents/young adults: 10-25 years
- Close contact with infected persons
- Crowded living (eg, dormitories and military barracks)
- Immunocompromised conditions such as asplenia, HIV infection, genetic polymorphisms, and complement deficiency
- Laboratory workers
- Low levels of serum bactericidal antibody (SBA)
- Low socioeconomic status and minority ethnicity
- Passive or active smoking
- Recent or concurrent upper respiratory infection, such as influenza
- Splenectomy (or functional asplenia)
- Travel to a hyperendemic or epidemic area
Etiology
- Meningococcemia is caused by N. meningitidis, an aerobic gram-negative diplococcus which lives exclusively in the human nasopharynx
- N. meningitidis adhere to non-ciliated columnar epithelial cells colonizing the naso/oropharynx
- These organisms are transmitted by inhalation of respiratory droplets or by direct contact with infected secretions
- Disseminated disease occurs when the organism enters the bloodstream after penetrating the nasal mucosa
[Outline]
History
- Nonspecific prodrome of cough, headache, sore throat, fever, chills, arthralgias, and myalgias. It is not uncommon for early presenters to be dismissed as viral syndrome; with the patient returning hours later critically ill
- Headache, neck stiffness, lethargy, nausea, vomiting and photophobia may be present in patients with meningitis accompanying meningococcemia
- Fulminant meningococcemia may lead to profound hypotension and vascular collapse within hours of onset of symptoms. In such cases, it is common so see dermatologic manifestations of petechiae and purpura
- Young children may have sudden fever, lethargy, vomiting, and/or seizures
Physical findings on examination
- Patients may initially not appear that unwell, but usually rapidly progress to becoming unwell (if seeing the patient early in the disease)
- Fever is common, but hypothermia or afebrile state may be present
- Patients with meningococcemia will usually appear severely ill, often with progressive signs of shock such as tachypnea, tachycardia, and hypotension
- Rapid deterioration is typical in fulminant cases, with profound vascular collapse, often with respiratory failure
- Petechiae can usually be found in areas such as the axilla, face, flank, ankle and wrist
- Purpuric lesions may occur, often in the same areas as petechiae, and are confluent areas of purple discoloration of the skin due to hemorrhage, hypercoagulability and necrosis
- Meningeal signs (Kernig's and Brudinski's) may be present
- Congestive heart failure, and pulmonary edema may be present with other evidence of end-organ damage (renal, adrenal dysfunction also common)
- Patients with serogroup C disease may present with or develop pericarditis during the illness
[Outline]
Blood test findings
- CBC and differential blood count: White blood cells (WBCs) may be elevated with a polymorphonuclear predominance. Neutropenia, thrombocytopenia and mild anemia may be present
- Blood cultures: Obtain at least 2 blood cultures while placing the initial 2 intravenous lines (this is immediately followed by first dose of antibiotic)
- Coagulation profile: Abnormalities may occur, such as a prolonged thrombin time, elevated fibrin degradation products or D-dimer, low fibrinogen or antithrombin levels, and thrombocytopenia
- Comprehensive panel: Examine for metabolic derangement (acidosis), hypokalemia is paradoxically present-despite acidosis in many cases, renal or hepatic dysfunction may be evident
- Venous or arterial blood gas: Can demonstrate acidosis, if oximetry is difficult due to hypoperfusion, an A-a gradient can be calculated, as well as determining actual PaO2
- C Reactive Protein (CRP): Can be useful in children to calculate the Rotterdam Score
which prognosticates a predicted death rate. The lower the CRP, the higher the death rate
Other laboratory test findings
- Cerebrospinal fluid (CSF): Lumbar puncture should be deferred in unstable or coagulopathic patients. Gram staining may show Gram-negative diplococci. In cases of meningitis, white blood cell counts are usually in the range of 500 to 50,000 cells/mm3 with polymorphonuclear predominance
- Polymerase chain reaction (PCR) analysis for diagnoses of central nervous system (CNS) infection. PCR of spinal fluid yields a sensitivity and specificity of >90% in the diagnosis of meningococcal meningitis
- Synovial fluid culture/analysis: If a joint is clearly involved and any underlying coagulopathy treated, aspiration for culture and fluid analysis is indicated
- Skin: Rarely, can be cultured from skin lesions
Radiographic findings- Chest x ray: Recommended in all cases as pulmonary involvement is not unusual. Lobar consolidation is typical in cases of meningococcal pneumonia, with or without pleural effusion. This test can also examine heart size and configuration in relation to potential pericardial effusion
- Head CT: Indicated in cases of altered level of consciousness, which can be due to meningitis or intracranial hemorrhage
Other diagnostic test findings
- Echocardiography: To evaluate for myocardial dysfunction and pericarditis
- Renal ultrasound: To assess adrenal hemorrhage
[Outline]
General treatment items
- Meningococcemia is a medical emergency. Patient's with this condition need urgent stabilization, typically in an emergency department, followed by admission to a tertiary level intensive care unit
- Antibiotics should be administered immediately with the starting of the second IV, and within minutes of arriving in an emergency department
- Airway, Breathing and Circulation must be stabilized. Intubation is commonly required early in the clinical course. Invasive monitoring, including central venous line for vasopressors and monitoring of central venous pressure (CVP), and arterial line for monitoring of blood pressure and arterial blood gases, are commonly needed
Resuscitation and supportive care: Hemodynamic, respiratory and metabolic support- Apply high flow oxygen
- IV fluids: Initial 10-20 mL/kg bolus of crystalloid (0.9% saline or Lactated Ringers) infused over minutes. After reassessment of patient status, continue with further boluses of crystalloid as needed to treat hypotension. It is not usual to require 20-60 mL/kg or more. This is followed by fluid infusion at a rate necessary to maintain parameters as listed below-vasopressors may be necessary to achieve these parameters:
- Urine output at >0.5 mL/kg/hour (pediatrics >1.0 mL/kg/hr)
- Mean arterial blood pressure at >65 mmHg (adults)
- Central venous pressure at 8-12 cm H2O
- Pulmonary capillary wedge pressure at 12-16 mmHg
- Cardiac index at
4 (L/min)/m2
- Vasopressors (unresponsive to fluid resuscitation with MAP65 mmHg):
- Dopamine 5-20 µg/kg/min IV, titrate to effect
- Epinephrine 0.1-1 mcg/kg/min, IV, titrate to effect
- Norepinephrine 0.04-0.5 mcg/kg/min IV, titrate to effect. Note that norepinephrine may be preferred over dopamine in septic shock, including in patients with poor cardiac output, as it may induce fewer cardiac arrhythmias. In patients with cardiogenic shock, a survival benefit over dopamine was demonstrated in one study
- Inotropic drugs (in low cardiac output with adequate left ventricular filling pressure):
- Dobutamine 2.5 mcg/kg/min IV initially, titrated as needed, range 2.5-20 mcg/kg/min
- Assisted ventilation if needed
Antibiotics:- Antibiotics should be administered early with broad empiric treatment. Although benzylpenicillin is probably the best treatment for confirmed meningococcemia; early in the clinical course, broader spectrum treatment is administered, pending confirmation of the diagnosis. Recommended empiric treatment is:
- Immunocompetent individuals:
- Cefotaxime:
- Adult: 2 g IV q6h
- Pediatric: 150-200 mg/kg/day IV divided q6-8h or
- Ceftriaxone:
- Adults: 2 g IV q12h
- Pediatric: 100 mg/kg/day IV divided q12-24h Plus
- Vancomycin:
- Adults: 1-1.5 g IV q12h
- Pediatric: 60 mg/kg/day divided q8h
- Immunocompromised individuals, infants 1 month of age, and adults >50 years, in addition to the above:
- Ampicillin:
- Adults: 2 g IV q4h
- Pediatric: 100-400 mg/kg IV divided q6h
- Once N. meningitidis has been identified:
- Ceftriaxone:
- Adults: 2 g IV q12h
- Pediatric: 100 mg/kg/day IV divided q12-24h
- or Penicillin G:
- Adults: 4 million units IV q4h
- Pediatric (>1 week old): 250,000-400,000 units/kg/day divided q4-6h
- Corticosteroids: Decreases neurological complications and in cases of meningitis should be administered before or with the first dose of antibiotic if possible
- Dexamethasone:
- Adults: 10 mg q6h
- Pediatric: 0.15 mg/kg IV q6h
Chemoprophylaxis:- Given to all household contacts, child care/nursery school contacts, and those exposed to secretions:
- Ceftriaxone:
- Adults: 250 mg IM single dose
- Pediatric: 125 mg single dose
- Ciprofloxacin 500 mg PO single dose
- Rifampin:
- Adult: 600 mg PO bid x 2 days
- Pediatric: 5-10 mg/kg/dose PO bid x 2 days
- Meningococcal vaccination: A meningococcal conjugate vaccine active against serogroups A, C, Y, and W-135 (but not against serogroup B) is recommended for routine vaccination for persons between 11 and 18 years old
Refer
General treatment items for detailed dosing
Disposition
Admission criteria
- Admit patient to ICU for patients with sepsis or meningitis-with respiratory isolation
Discharge criteria
- Condition completely treatment, hemodynamics stable, back at normal state or improved maximally and stable for discharge
- Prophylaxis for close patient contacts
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