Approach Considerations
As mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral antibiotics by means of an intravenous (IV) or intramuscular (IM) route as soon as the diagnosis is suspected. [90] The IM administration of medications should be avoided in cases with shock because decreased tissue perfusion severely limits their delivery to the infected sites.
Other than antimicrobial treatment, supportive measures in meningococcal disease may be required to correct circulatory collapse. Severe adrenal insufficiency requires corticosteroid replacement. [3]
Chemoprophylaxis for meningococcal infection should be administered to intimate household, daycare center, and nursery school contacts of cases. Vaccinate household and other intimate contacts.
Although increasingly well recognized and managed in children, meningococcal disease often is not diagnosed and treated in adults in medical settings. Fluid resuscitation may not be sufficiently aggressive, early intubation often is not considered, and the rapidity of disease progression in an adult often is not understood.
Treatment of complications
Arthritis has been found in about 10% of patients with meningococcal disease. This complication usually occurs within the first few days of treatment and manifests as effusion of a large joint, often the knee. Occasionally, repeated arthrocentesis is needed to control symptoms.
Other possible complications include ischemic conditions caused by the coagulation abnormality and neurologic complications of meningitis. The patient must be observed for any neurologic sequelae; the frequency of neurologic abnormalities seems to be related to the severity of the acute disease. Some neurologic sequelae can develop in the absence of meningitis.
Inpatient care
Hospitalization usually is required for all patients even if only adequately monitor their response to antibiotic and other therapies. Promptly begin antibiotic treatment. Respiratory precautions generally include placement of the patient in a private room with proper air handling and the use of a respiratory mask by any person entering the patient's room. Discontinue respiratory isolation precautions after 24 hours of antibiotics.
Monitor blood pressure, urine output, and cardiac function, as well as platelets, fibrin, and fibrin degradation products.
Transfer to a PICU is necessary in approximately 20% of pediatric cases of meningococcal infection.
Guidelines
Several clinical guideline summaries related to meningococcal disease are available, as follows:
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American Academy of Pediatrics Committee on Infectious Diseases - Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients [5]
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Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices - Prevention and control of meningococcal disease [91]
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European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline - Diagnosis and treatment of acute bacterial meningitis [92]
Emergency Management of Meningococcal Infection
Although many meningococcal infections rapidly improve when treated with antibiotics, meningococcal disease may quickly progress. The time from the appearance of the first symptoms to death may be only a few hours.
Because the mortality rate of meningococcal disease maybe as high as 40%, all patients with fever and petechiae warrant rapid initial assessment and empiric and ongoing assessment.
The following findings may help in the identification of severely ill patients whose condition may deteriorate and who are likely to need intensive care:
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Shock/hypotension
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Absence of meningitis
-
Rapidly extending rash
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Low WBC count
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Coagulopathy
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Deteriorating level of consciousness
-
Increased ICP is more common in isolated cases of meningococcal meningitis.
Managing shock
After basic life support and antibiotics are administered, the next priority is treating shock/hypotension with initial volume replacement at a rate of 20mL/kg. A satisfactory response to volume replacement is a reduction in heart rate and improved peripheral perfusion. The patient's condition may stabilize with only volume replacement, but the patient requires close monitoring and reassessment to detect further signs of shock or pulmonary edema (due to capillary leak syndrome).
Managing raised intracranial pressure
Suspect increased ICP if the patient has a decreased level of consciousness; focal neurologic signs; unequal, dilated, or poorly reacting pupils; abnormal posturing or seizures; relative hypertension or bradycardia; or if the patient is agitated or combative. Because papilledema is a late sign of increased ICP, its absence early on does not justify the discontinuance of monitoring for its development.
After initiating basic life support measures and administering antibiotics, the therapeutic goal is to maintain oxygen and nutrient delivery to the brain. For this reason, shock must be corrected in individuals with both shock and increased ICP to maintain cerebral perfusion pressure. After correcting shock/hypotension with volume replacement and inotropic support as necessary, cautiously manage the fluid balance to avoid further increasing the ICP.
Performance of a lumbar puncture should always be avoided
Treatment of patients with limited shock and no increased ICP
Reassess patients with limited shock and no increased ICP, as well as patients who respond rapidly to minimal volume replacement, for signs of deterioration during the first 48 hours following admission.
The use of corticosteroids in meningitis may be considered. Several studies revealed that adjunctive dexamethasone reduces sensorineural hearing loss (but not mortality or other neurologic sequelae) in children and infants with H influenzae type B meningitis. Few adverse effects occur with dexamethasone administration. No reports of delayed CSF sterilization or treatment failure are known. A meta-analysis of findings from randomized, controlled trials suggested that such treatment has a benefit in preventing sequelae in meningococcal meningitis and pneumococcal meningitis in childhood.
Data are limited for meningococcal meningitis, and the pathophysiologic events are likely to be similar to those of other forms of bacterial meningitis. In some animal models, anti-inflammatory therapy was beneficial. No evidence of the benefits of steroid use in patients with septic shock is known, and steroid use is necessary only with meningitis.
If hypoadrenalism is suspected because of resistance to large doses of inotropic drugs, administer adrenal replacement doses of hydrocortisone.
Replacement corticosteroids should not be used routinely in pediatric sepsis; their use is controversial in adult sepsis. [93, 94]
Pharmacologic Therapy
The most important measure in treating meningococcemia is early detection and rapid administration of antibiotics. Third-generation cephalosporins such as ceftriaxone or cefotaxime are preferred because of their effectiveness and ease of administration.
Meningococci are resistant to vancomycin, polymyxin, or achievable serum levels of aminoglycoside antibiotics.
Empiric therapy
Empiric antibiotic therapy should provide coverage of likely meningeal pathogens when no rash is present, when the etiology of meningitis is uncertain, and when an immediate microbiologic diagnosis is unavailable. This therapy can be narrowed down to specific therapy when the specific pathogen and its antibiotic sensitivities are determined.
A third-generation cephalosporin is the appropriate antibiotic until culture results are available. Although meningococcal infection is the most common bacterial cause of a petechial or purpuric rash and meningitis, other organisms (including H influenzae type B and Streptococcus pneumoniae) can cause shock and a nonblanching rash.
H influenzae type B is an uncommon cause of meningitis in developed countries with comprehensive vaccination programs. Most cases of bacterial meningitis that occur outside of the United States are due to N meningitides, with the rest resulting from S pneumoniae. In the United States, S pneumoniae is predominant.
Empiric antibiotic therapy for meningitis based on age is as follows:
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Neonates - Ampicillin and ceftriaxone/cefotaxime
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Infants aged 1-3 months - Ampicillin and ceftriaxone/cefotaxime
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Older infants, children, and adults - Cefotaxime or ceftriaxone
Chloramphenicol 100 mg/kg/day in 4 divided doses (up to 4 g/day maximum dose) can be given as an alternative. Because there may be increased mortality compared with other regimens, it is no longer recommended as a first-line treatment. [95]
Dexamethasone is indicated in the treatment of known or suspected pneumococcal meningitis in adults and children with H influenzae type B meningitis. Although of no benefit in meningococcal meningitis, it can be given until the causative organism is identified. [95]
Surgical Treatment of Ischemic Complications
Patients who survive the initial acute phase of fulminant meningococcemia are at increased risk for serious complications due to extensive tissue necrosis. [96]
Early in the course of tissue injury, conservative therapy is recommended until a distinct line of demarcation is apparent between viable and nonviable tissue.Once the patient is stable, débridement of all necrotic tissue is essential and may necessitate extensive removal of skin, subcutaneous tissue, and muscle. Large defects may be covered using microvascular free flaps or skin grafts. The use of artificial skin can spare the patient immediate use of autograft sites, which frequently are limited. [97] Avoid early limb amputation, because significant tissue recovery may occur as the disease progresses.
Poor tissue perfusion also may lead to dental complications that require extensive extraction of severely affected teeth. [98]
Anecdotally, fasciotomy may preserve limb and digit function in severe meningococcal septicemia when impending peripheral gangrene and increased compartment pressures are present. Measure compartment pressures and assess peripheral pulses with Doppler ultrasonography when patients have impaired limb perfusion or severe edema.
Monitoring and Follow-Up
Pericarditis can occur during the recuperative period. It may present with fever and shortness of breath upon minimal exertion.
Late skeletal deformities are rare, but epiphyseal avascular necrosis and epiphyseal-metaphyseal defects have been described. These usually occur in the lower extremities and result in angular deformity and inequality of leg length.
Observe patients for any late neurologic sequelae. Abnormal findings on electroencephalography or cerebral computed tomography (CT) scanning, as well as epileptogenic activity, sensorineural hearing loss, impaired vestibular function, and neuropsychological impairment, have been found in up to 30% of survivors 1 year after an episode of meningococcal disease. The frequency of serious neurologic sequelae in individuals who survive an episode is 3%.
Follow-up care at least 6 weeks after meningococcal infection should include the following:
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Ongoing management of specific complications such as amputations, skin grafting, or renal failure
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Thorough physical and nerological examination
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Assessment of plasma complement levels - Eg, total hemolytic complement, C3, and C4, with or without properdin
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Serologic confirmation of the diagnosis if no diagnosis was made at the time of presentation
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Audiologic function testing
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Basic assessment of psychological status after intensive care, if relevant
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Possible vaccination of contacts if an outbreak of group A, C, Y, or W-135 disease occurs
Vaccine
High-risk individuals
Specific categories of individuals at high risk for meningococcal disease include the following [99] :
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Laboratory workers
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Patients with HIV
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Military recruits
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Outbreaks with type B among college freshmen living in dormitories
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Travelers to endemic zones (sub-Saharan Africa)
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Deficiencies of terminal complement including vaccinated patients on eculizumab
-
Men who have sex with men (MSM) can develop urethritis due to an anaerobic tolerant clade of N meningitidis that facilitates rectal/urethral transmission. In this population, Gram negative diplococci should not be assumed to represent N gonorrhea.
-
Individuals with asplenia
Table 1. Guidelines on Meningococcal B Vaccination by the Advisory Committee on Immunization Practices [100, 101] (Open Table in a new window)
Patient population |
Conditions |
Vaccine Regimen |
Persons aged 10 years or older at increased risk for serogroup B meningococcal disease |
In high-risk persons and during serogroup B meningococcal disease outbreaks |
3 doses of MenB-FHbp at 0, 1-2, and 6 months to provide earlier protection and maximize short-term immunogenicity. If the second dose of MenB-FHbp is administered at an interval of 6 months or greater, a third dose need not be given. |
Adolescents and young adults aged 16-23 years |
Healthy adolescents and young adults |
2 doses of MenB-FHbp at 0 and 6 months. If the second dose of MenB-FHbp is given less than 6 months after the first dose, give a third dose at least 4 months after the second dose. |
Pregnant or lactating individuals |
Defer vaccination unless the person is at increased risk for serogroup B meningococcal disease and their healthcare provider determines benefits outweigh potential risks. |
The recommendations include the following:
-
Recommendations for use of MenB-4C vaccine are unchanged.
-
The two MenB vaccines are not interchangeable, and the same product must be given for all doses in a series.
Table 2. Recommendations for Meningococcal Vaccine According to Type of Patient (Open Table in a new window)
Type of patient |
Vaccine type |
Regimen |
11-18 years old |
Quadrivalent ACWY vaccines |
One dose at age 11-12 years and booster at 16 years |
19–21 years old |
Quadrivalent ACWY vaccines +/- serogroup B vaccines |
Freshman in college dormitories should receive serogroup B vaccines |
Prevention of Secondary Cases
Antimicrobial chemoprophylaxis of close contacts is the primary means of preventing secondary cases of sporadic meningococcal disease. Person-to-person transmission can be interrupted by administration of an antimicrobial that eradicates the asymptomatic nasopharyngeal carrier state. Sulfonamides, rifampin, minocycline, ciprofloxacin, and ceftriaxone are the drugs that have been shown to eradicate meningococci from the nasopharynx.
Because the rate of disease in secondary contacts is highest immediately after the onset of the disease in the patient, chemoprophylaxis should be administered as soon as possible, preferably within 24 hours. If chemoprophylaxis is delayed by more than 14 days, it probably is of limited value, although it still is recommended until 4 weeks after the patient's presentation.
Populations at Risk for Secondary Cases
Meningococcal infection probably is introduced into families by asymptomatic adults and then spread through 1 or more household contacts to infect younger family members. Household contacts are defined as individuals who live in the same home with a person who has a meningococcal disease. An operational definition commonly used by public health authorities includes persons eating and sleeping under the same roof as the index case.
The attack rate of meningococcal disease among household contacts has been estimated to be several hundred times greater than that in the general population. The secondary attack rate is inversely proportional to age and is estimated to be approximately 10% in household contacts aged 1-4 years. Among adults, the risk is 3-4%.
It should be assumed that the risk of acquiring meningococcal disease is signifcantly increased in other closed populations, such as those of daycare facilities and nursery schools.
Healthcare workers who are exposed to aerosol secretions from patients with meningococcal disease are 25 times more likely to contract the disease compared with the general population.
The likelihood of acquiring infection is increased 100-1000 times in sexually intimate contacts of individuals with meningococcemia.
Indications for Chemoprophylaxis
The American Academy of Pediatrics recommends antimicrobial chemoprophylaxis for contacts of persons with invasive meningococcal disease, including household members, individuals at daycare centers and nursery schools, and persons directly exposed to the patient's oral secretions (eg, kissing, sharing of food or beverages) within the 7 days preceding the onset of the illness in the index case.
Consider antimicrobial chemoprophylaxis in hospital personnel who have had direct exposure to the oral secretions of a patient with meningococcal disease from such activities as mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management.
To further decrease the risk for infection in the clinical setting, staff caring for patients with known or suspected meningococcal infections should wear masks, in addition to taking standard precautions.
Patients with meningococcal disease who are hospitalized should be placed on respiratory precautions for the first 24 hours of effective antimicrobial therapy. When this is done, the risk for hospital personnel with casual or indirect contact is believed to be negligible. Antimicrobial chemoprophylaxis is not recommended in hospital personnel who have only casual or indirect contact with a patient with meningococcal disease.
For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index patient or for anyone seated directly next to an index patient on a prolonged flight (ie, one that lasts ≥8h).
Antibiotic chemoprophylaxis appears to be most effective if administerd within 24 h of contact. Little, if anything, is gained if given beyond 7days.
Prophylactic Antibiotics
Rifampin
Rifampin commonly is used for meningococcal prophylaxis of household contacts in the United States; a 2-day oral course is recommended.
Children younger than 1 month: 5mg /kg q12h
Children older than 1 month: 10 mg/kg q12h
Adults: 600mg q1h
Ciprofloxacin
Children younger than 18 years: not recommended because it has caused cartilage damage in immature experimental animals.
Adults: A single dose of ciprofloxacin (500 mg) is an effective alternative to rifampin for the eradication of meningococcal carriage in adults.
Ceftriaxone
A single IM injection of ceftriaxone eradicates meningococcal carriage. Ceftriaxone is preferred in children who refuse oral medication and may be used in pregnancy.
Children younger than 15 years: 125 mg IM
Adults: 250 mg IM
Meningococcal disease can be prevented by vaccination with group-specific meningococcal capsular polysaccharides. [91] Purified polysaccharides of groups A, C, Y, and W-135 meningococci have been used to stimulate group-specific humoral bactericidal antibodies.
Consultations
Consultations in meningococcal disease include the following:
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Surgery - In cases involving gangrene of the extremities
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Hematology - May be needed to manage coagulopathy
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Cardiology - in cases with evidence of heart failure or pericarditis
-
Infectious Disease - Required for all cases
-
Preventive medicine specialist - To evaluate the community risk associated with an index case and to initiate reporting to local and regional health authorities if indicated
-
Orthopedist and/or vascular surgeon
Local department of health to be notified of suspected and/or proven cases of meningococcal infection to assist in the evaluation and treatment of close contacts.
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Dorsum of the hand showing petechiae. Courtesy of Professor Chien Liu.
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Petechiae on the palm. Courtesy of Professor Chien Liu.
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Petechiae on lower extremities. Courtesy of Professor Chien Liu.
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Conjunctival petechiae. Courtesy of Professor Chien Liu.
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Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.
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Scattered petechiae in a patient with acute meningococcemia.
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Purpura in a young adult with fulminant meningococcemia.
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The legs of a 22-year-old woman in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.
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A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.
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The leg of a 9-month-old infant in septic shock with a rapidly evolving purpuric rash. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.
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Neisseria meningitis purpuric lesions on the ear and cheek of a 9-month-old infant who is in septic shock. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.
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Lesions caused by Neisseria meningitis bacteremia on the palm of the hand of a 9-month-old infant. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.
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Areas with frequent epidemics of meningococcal disease. This is known as the meningitis belt of Africa; visitors to these locales may benefit from meningitis vaccine. Image courtesy of CDC.
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Child with severe meningococcal disease and purpura fulminans.
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Flow chart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical areas and are available at Meningitis.org.
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Flow chart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clinical areas and are available from Meningitis.org.
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Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).
Tables
Patient population |
Conditions |
Vaccine Regimen |
Persons aged 10 years or older at increased risk for serogroup B meningococcal disease |
In high-risk persons and during serogroup B meningococcal disease outbreaks |
3 doses of MenB-FHbp at 0, 1-2, and 6 months to provide earlier protection and maximize short-term immunogenicity. If the second dose of MenB-FHbp is administered at an interval of 6 months or greater, a third dose need not be given. |
Adolescents and young adults aged 16-23 years |
Healthy adolescents and young adults |
2 doses of MenB-FHbp at 0 and 6 months. If the second dose of MenB-FHbp is given less than 6 months after the first dose, give a third dose at least 4 months after the second dose. |
Pregnant or lactating individuals |
Defer vaccination unless the person is at increased risk for serogroup B meningococcal disease and their healthcare provider determines benefits outweigh potential risks. |
Type of patient |
Vaccine type |
Regimen |
11-18 years old |
Quadrivalent ACWY vaccines |
One dose at age 11-12 years and booster at 16 years |
19–21 years old |
Quadrivalent ACWY vaccines +/- serogroup B vaccines |
Freshman in college dormitories should receive serogroup B vaccines |
Patient population |
Conditions |
Vaccine Regimen |
Persons aged 10 years or older at increased risk for serogroup B meningococcal disease |
In high-risk persons and during serogroup B meningococcal disease outbreaks |
3 doses of MenB-FHbp at 0, 1-2, and 6 months to provide earlier protection and maximize short-term immunogenicity. If the second dose of MenB-FHbp is administered at an interval of 6 months or greater, a third dose need not be given. |
Adolescents and young adults aged 16-23 years |
Healthy adolescents and young adults |
2 doses of MenB-FHbp at 0 and 6 months. If the second dose of MenB-FHbp is given less than 6 months after the first dose, give a third dose at least 4 months after the second dose. |
Pregnant or lactating individuals |
Defer vaccination unless the person is at increased risk for serogroup B meningococcal disease and their healthcare provider determines benefits outweigh potential risks. |
