Pediatric Meningococcal Infections Treatment & Management

  • Author: Saul N Faust, MA, MBBS, PhD, MRCPCH; Chief Editor: Russell W Steele, MD   more...
 
Updated: May 2, 2011
 

Medical Care

Medical care of meningococcal infections should address community management, antimicrobial treatment, and emergency management of meningococcal septicemia and meningitis,[1] which may include treating shock and increased intracranial pressure (ICP) and the use of new and experimental therapies.[9]

  • Community management
    • Because mortality may be reduced with early antibiotic therapy, patients with a meningococcal rash should receive parenteral antibiotics by means of an intravenous or intramuscular route as soon as the diagnosis is suspected. In the United Kingdom, prehospital treatment with benzylpenicillin is recommended.[13]
    • Intramuscular antibiotic injections may be less effective in a patient with shock and poor tissue perfusion.
    • For information regarding family practice recognition and management of meningococcal disease, see the image below. Additional resources are available at Meningitis.org. Chart for family practice recognition and managemeChart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).
  • Antimicrobial treatment
    • 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.
    • Empirical antibiotic therapy ensures coverage of likely meningeal pathogens when no rash is present, when the etiology of meningitis is uncertain, and when an immediate microbiological diagnosis is unavailable. This therapy can be modified in favor of appropriate specific therapy when the organism is grown or when its antibiotic sensitivities are known.
    • Although H influenzae type B is now an uncommon cause of meningitis in developed countries with modern vaccination programs, antibiotic therapy should cover this organism. Most cases of bacterial meningitis are due to N meningitides, and most other cases are due to S pneumoniae. In the United States, most cases are due to S pneumoniae.
    • Pneumococcal resistance to high-dose third-generation cephalosporins is reported in the United States and in some European countries, although resistance is unusual in the United Kingdom. For this reason and because untreated or partially treated bacterial meningitis has a poor outcome, the use of vancomycin and a third-generation cephalosporin is recommended for the treatment of suspected pneumococcal meningitis until the organism is identified and its sensitivities are known. Discontinue vancomycin after the microbial diagnosis and antibiotic sensitivities are established.
    • Empirical antibiotic therapy for meningitis based on age is as follows:
      • Neonates - Ampicillin and cefotaxime (or ampicillin and gentamicin)
      • Infants aged 1-3 months - Ampicillin and cefotaxime with or without vancomycin
      • Older infants, children, and adults - cefotaxime or ceftriaxone with or without vancomycin
    • In 2007 the US Food and Drugs Administration (FDA) issued an alert that led to changes in the prescribing information for ceftriaxone. Dilution, mixing, or y-site infusion with calcium-containing intravenous (IV) solutions may increase risk for precipitant to formin vivo. Initially, the FDA recommended that ceftriaxone no longer be administered within 48 hours of the completion of calcium-containing solutions, including parenteral nutrition, regardless of whether the drugs were administered by different infusion catheters.[14, 15]
    • In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MRHA) issued a drug safety bulletin stating that ceftriaxone should not be given simultaneously with calcium-containing infusions.[16] However, in April 2009, the FDA has changed its advice and no longer cautions the use of ceftriaxone and calcium-containing solutions, except in neonates younger than 28 days.[17] The MRHA in the UK have not yet changed their advice.
    • For information about emergency management of meningococcal disease in children, see below.Flowchart shows guidelines for the emergency managFlowchart 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. Flowchart shows guidelines for the emergency managFlowchart 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.
  • Emergency management of meningococcal septicemia and meningitis
    • Although many meningococcal infections rapidly improve when treated with antibiotics, in some cases, meningococcal disease may progress rapidly; the time lag from the appearance of the first symptoms to death may be only a few hours.
    • Because the mortality rate is 10%, all patients with fever and petechial rash warrant urgent initial assessment and treatment and subsequent careful and repeated assessment. The initial assessment should be conducted to identify major clinical problems.
    • The following findings may help in the identification of severely ill patients whose condition may deteriorate and who are likely to need intensive care:
      • Shock
      • Absence of meningitis
      • Rapidly extending rash
      • Low WBC count
      • Coagulopathy
      • Deteriorating level of consciousness
    • Shock and increased ICP, which are underlying processes in meningococcal disease that lead to death, may coexist. Increased ICP is more common in patients with only meningitis.
  • Managing shock
    • After basic life support and antibiotics are administered, the next priority is treating shock. Basic life support should include the administration of oxygen at a rate of 10-15 L/min by means of a facial mask.
    • Any patient with cool extremities, prolonged capillary refill time, and tachycardia should be considered to have shock.
    • The initial therapy for shock is volume replacement at a rate of 20 mL/kg. In the United Kingdom, the use of 4.5% human albumin solution is generally recommended, although some US and UK centers use normal saline. A satisfactory response to volume replacement is a reduction in heart rate and improved peripheral perfusion. The first bolus of fluid may be repeated to achieve this response. 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). The goal of circulatory support is to maintain tissue perfusion and oxygenation.[18]
    • Patients who do not respond to initial volume replacement require further volume replacement and may need inotropic support, such as the use of dopamine or dobutamine (10-20 mcg/kg/min), which may be administered via a peripheral vein until central venous access is established. Patients with persistent hypotension may need an infusion of adrenaline (0.1-5 mcg/kg/min), which must be administered via central venous access.
    • Endotracheal intubation and ventilation are recommended in patients who still have signs of shock after they have received volume replacement of more than 40 mL/kg. Even patients who are apparently awake and alert have a high risk of pulmonary edema.
    • Some patients require fluid replacement with as much as twice their circulating blood volume in the first hours after presentation, but additional volume should be administered only after positive pressure ventilation is established.
    • Biochemical correction of acidosis, hypoglycemia, hypokalemia, hypocalcemia, and hypomagnesemia is usually required.
    • Correct coagulopathy and anemia with the use of fresh frozen plasma and blood, as appropriate.
  • Managing raised ICP
    • Suspect increased ICP if the patient has a decreased level of consciousness; focal neurological signs; unequal, dilated or poorly reacting pupils; abnormal posturing or seizures; relative hypertension or bradycardia; or if the patient is agitated or combative. Papilledema is a late sign; therefore, its absence should not reassure the treating team because raised ICP can still be present.
    • After initiating basic life support principles 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 with volume replacement and inotropic support as necessary, cautiously manage the fluid balance to avoid further increasing the ICP.
    • Consider the use of mannitol (0.25 g/kg IV over 10 min), followed by furosemide (1 mg/kg IV) when increased ICP is suspected. These drugs can help control the ICP during elective intubation.
    • Immediately institute measures to stabilize the ICP; these measures may include intubation and ventilation in order to control PaCO2 between 4-4.5 kPa, sedation and muscle relaxation, and elevating the patient's head by 30 degrees.
    • Find and correct biochemical abnormalities.
    • Do not attempt lumbar puncture.
    • Treat seizures, if present, using standard resuscitation guidelines
  • Treatment of patients with limited shock and no increased ICP
    • Reassess these patients and 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 neurological 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 suggests that such treatment has a benefit in preventing sequelae in both this and pneumococcal meningitis in childhood.
    • Although data are poor for meningococcal meningitis, 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. Steroids have not yet been proven helpful in septicemia.
  • New and experimental therapies for meningococcal septicemia: Although new and experimental therapies have been proposed, none have proven to reduce mortality or morbidity. Therapies include the following:
    • Antiendotoxin agents: An international multicenter randomized controlled trial of the antiendotoxin recombinant bactericidal permeability-increasing protein was recently completed at centers in the United Kingdom and United States.[19] Despite a strong trend in reducing mortality and amputations, the benefits were not statistically significant. Further studies are being designed. A randomized trial of the use of antiendotoxin monoclonal antibody HA1A in children with meningococcemia showed a 32% reduction in mortality, but the result was not statistically significant (n = 269, P = .110).
    • Anticytokine response agents (eg, monoclonal antibody against tumor necrosis factor[20] )
    • Leukocyte activation antagonists (eg, corticosteroids)
    • Peripheral vasodilators (eg, prostacyclin)
    • Agents for the treating disseminated intravascular coagulation (eg, protein C[21] or activated protein C[22] )
    • Agents for treating acute respiratory distress syndrome (eg, extracorporeal membrane oxygenation [randomized controlled trials not performed])
    • Miscellaneous agents (eg, hemodiafiltration [randomized controlled trials not performed])
    • Corticosteroids: A phase 2 multicenter 2 pilot study is underway in the United Kingdom to examine the safety and endocrine/inflammation/coagulation profiles seen in low dose replacement corticosteroid therapy for sepsis in children and to inform a large multicenter trial. Replacement corticosteroids should not currently be used routinely in pediatric sepsis (and are now controversial in adult sepsis).[23, 24]
    • Treatment of hyperglycemia on pediatric ICU (PICU) in critically ill children: Currently, whether hyperglycemia in critically ill patients on PICU should be treated with insulin is under debate. Van den Berghe published the results of a trial in 2001 in adult surgical patients which showed decreased mortality in ICU patients with tight glycemic control (on insulin).[25] In 2006, a repeat study showed no mortality benefit and a significantly increased risk of hypoglycemia. A recent study in the United Kingdom showed poorer outcomes in patients with hyperglycemia on PICU (no insulin therapy used).[26] A large multicenter trial is underway in the United Kingdom to examine the control of hyperglycemia in critically ill children in the PICU.
Next

Surgical Care

  • Anecdotally, fasciotomy may preserve limb and digit function in severe meningococcal septicemia when impending peripheral gangrene and increased compartment pressures are present.
  • Consult an orthopedist, vascular surgeon, or both.
  • Measure compartment pressures and assess peripheral pulses with Doppler ultrasonography when patients have impaired limb perfusion or severe edema.
  • Avoid early limb amputation because significant tissue recovery may occur as the disease progresses.
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Contributor Information and Disclosures
Author

Saul N Faust, MA, MBBS, PhD, MRCPCH  Senior Lecturer in Pediatric Immunology and Infectious Diseases, University of Southampton; Director, Wellcome Trust Clinical Research Facility, Southampton University Hospitals NHS Trust, UK

Saul N Faust, MA, MBBS, PhD, MRCPCH is a member of the following medical societies: British Paediatric Allergy, Immunology and Infectious Group, European Society for Paediatric Infectious Diseases, International Society for Infectious Diseases, and Royal College of Paediatrics and Child Health

Disclosure: Xoma Consulting fee Consulting; GSK Honoraria Consulting; Wyeth travel and registration fee to conference investigator in study being presented at meeting; Sanofi Pasteur Consulting fee Consulting; Pfizer Consulting fee Consulting

Coauthor(s)

Katrina Cathie, BM(Hons), MRCPCH  Academic Clinical Fellow, Southampton University, UK

Katrina Cathie, BM(Hons), MRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Michael Levin, PhD, FRCP, FRCPCH  Head, Professor, Imperial College School of Medicine at St Mary's Hospital, Department of Pediatrics, London, England

Disclosure: Nothing to disclose.

Specialty Editor Board

David Jaimovich, MD  Chief Medical Officer, Joint Commission International and Joint Commission Resources

David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Joseph Domachowske, MD  Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Sanofi Pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

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Child with severe meningococcal disease and purpura fulminans.
Flowchart 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.
Flowchart 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.
Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).
Family practice booklet describing management of meningococcal disease in the community (courtesy of Meningitis.org).
 
 
 
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