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Meningococcal Disease

- CBC with differential - Leukocytosis (left shift; toxic granulation) or leukopenia, thrombocytopenia

- Lactic acidosis - Coagulation studies - Prolonged prothrombin time/partial thromboplastin time - Low fibrinogen - Elevated fibrin degradation products

- CSF - Grossly cloudy - Increased WBCs with polymorphonuclear predominance - 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) - CSF culture for N. meningitidis: positive in 80 " 90% of cases

- Antibiotics - Begin teatment as soon as meningococcal meningitis is suspected. - Age influences empiric treatment based on common etiologic organisms. - Preterm to <1 month: ampicillin plus cefotaxime or ampicillin plus gentamicin - Cefotaxime - 0 to7 days: 50 mg/kg q12h - 8 to 28 days: 50 mg/kg q8h

- Duration of treatment: 7 days (6) - Dexamethasone - Indications - Known or suspected pneumococcal meningitis in selected adults - Children with H. influenzae type B meningitis

- Dexamethasone is often given initially in adults and children with suspected bacterial meningitis while awaiting microbiologic data. - Dexamethasone has not been shown to be of benefit in meningococcal meningitis and should be discontinued once this diagnosis is established. - Dosage - Infants and children >6 weeks: IV 0.15 mg/kg/dose q6h for the first 2 to 4 days of antibiotic treatment - Start 10 to 20 minutes before or with the first dose of antibiotic.

- Timing - Ideally <24 hours after case identification - Chemoprophylaxis should not be administered if identified >14 days after exposure.

- Prophylactic regimens - Rifampin, ciprofloxacin, and ceftriaxone - Ceftriaxone - Recommended for pregnant women - Adults: 250 mg IM as a single dose

- Precautions - Adjust the dosage of medications in patients with severe renal dysfunction.

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  • Isolation of N. meningitidis from a sterile site (blood or CSF) is the gold standard for diagnosing systemic meningococcal infection.
  • Antibiotic administration may render blood and/or CSF culture negative within 2 hours. Treat, then test.

Initial Tests (lab, imaging)

  • CBC with differentialLeukocytosis (left shift; toxic granulation) or leukopenia, thrombocytopenia
  • Lactic acidosis
  • Coagulation studiesProlonged prothrombin time/partial thromboplastin timeLow fibrinogenElevated fibrin degradation products
  • Blood cultureBlood culture positive for N. meningitidisCultures positive in 50 " 60% of cases
  • CSFGrossly cloudyIncreased WBCs with polymorphonuclear predominanceGram stain showing gram-negative diplococciGlucose-to-blood glucose ratio <0.4Protein >45 mg/dLPositive for N. meningitidis antigen (MAT or PCR)CSF culture for N. meningitidis: positive in 80 " 90% of cases
  • CT scan of head if concern for space-occupying lesions

Test Interpretation

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

TREATMENT

MEDICATION

First Line

  • AntibioticsBegin teatment as soon as meningococcal meningitis is suspected.Age influences empiric treatment based on common etiologic organisms.Preterm to <1 month: ampicillin plus cefotaxime or ampicillin plus gentamicinCefotaxime0 to7 days: 50 mg/kg q12h8 to 28 days: 50 mg/kg q8hAmpicillin>2,000 g0 to 7 days: 50 mg/kg q8h8 to 28 days: 50 mg/kg q6h<2,000 g0 to 7 days: 50 mg/kg q12h8 to 28 days: 50 mg/kg q8h1 month to 50 years: cefotaxime or ceftriaxone plus vancomycinIf severe penicillin allergy: chloramphenicol plus trimethoprim-sulfamethoxazole (TMP-SMX) plus vancomycin>50 years of age or patients with alcoholism, debilitating disease, or impaired immunity: ampicillin plus ceftriaxone plus vancomycinAmpicillin: 2 g IV q4hCeftriaxone: 2 g IV q12hVancomycin: 30 to 45 mg/kg/day IV divided q6hIf severe penicillin allergy: TMP-SMX plus vancomycinPenicillin GEffective if the isolate is penicillin sensitivePenicillin can be used if the isolate has a penicillin minimum inhibitory concentration (MIC) of <0.1 Όg/mL.For isolates with a penicillin MIC of 0.1 to 1 Όg/mL, treatment with high-dose penicillin is effective, but a 3rd-generation cephalosporin is preferred (5).Penicillin G: 4 million units IV q4h (pediatric dose: 0.25 mU/kg/day IV divided q4 " 6h) OR ampicillin: 2 g IV q4h (pediatric dose: 200 to 300 mg/kg/day IV divided q6h)
  • Duration of treatment: 7 days (6)
  • DexamethasoneIndicationsKnown or suspected pneumococcal meningitis in selected adultsChildren with H. influenzae type B meningitis
  • Dexamethasone is often given initially in adults and children with suspected bacterial meningitis while awaiting microbiologic data.
  • Dexamethasone has not been shown to be of benefit in meningococcal meningitis and should be discontinued once this diagnosis is established.
  • DosageInfants and children >6 weeks: IV 0.15 mg/kg/dose q6h for the first 2 to 4 days of antibiotic treatmentStart 10 to 20 minutes before or with the first dose of antibiotic.
  • ChemoprophylaxisIndicationsClose contacts: Those who have had prolonged (>8 hours) contact while in close proximity (<3 feet) to the patient or who have been directly exposed to the patient 's oral secretions between 1 week before the onset of the patient 's symptoms and until 24 hours after initiation of appropriate antibiotic therapy (2).Examples: household members and personnel in nurseries, daycare centers, nursing homes, dormitories, military barracks, correctional facilities, and other closed institutional settingsNo chemoprophylaxis is indicated for casual contacts, including most health care workers, unless there is exposure to respiratory secretion.TimingIdeally <24 hours after case identificationChemoprophylaxis should not be administered if identified >14 days after exposure.Prophylactic regimensRifampin, ciprofloxacin, and ceftriaxoneCeftriaxoneRecommended for pregnant womenAdults: 250 mg IM as a single doseRifampin (meningococcal meningitis prophylaxis)Adult: 600 mg IV or PO q12h for 2 daysPediatric<1 month: 10 mg/kg/day in divided doses q12h for 2 daysInfants and children: 20 mg/kg/day in divided doses q12h for 2 days (max 600 mg/dose)CiprofloxacinAdults: 500 mg PO as a single dose (7)[B]
  • VaccinationFor household contacts (if the case is from a vaccine-preventable serogroup)
  • PrecautionsAdjust the dosage of medications in patients with severe renal dysfunction.

Second Line

  • For meningitisChloramphenicol: 1 g IV q6h (pediatric dose: 75 to 100 mg/kg/day divided q6h) or ceftriaxone 2 g IV q12h (pediatric dose: 80 to 100 mg/kg/day divided q12 " 24h)In large outbreaks, a single dose of long-acting chloramphenicol has been used. Single-dose ceftriaxone shows equal efficacy in one randomized controlled trial.
  • PrecautionsCeftriaxone should not be used in patients with a history of anaphylactic reactions to penicillin (e.g., hypotension, laryngeal edema, wheezing, hives).Chloramphenicol may cause aplastic anemia.

ISSUES FOR REFERRAL

Potential complications

  • Seizure activity
  • DIC
  • Acute respiratory distress syndrome
  • Renal failure
  • Adrenal failure
  • Multisystem organ failure

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • If meningitis is suspected, initiate antibiotics ( ± corticosteroids), and proceed immediately to lumbar puncture.
  • Droplet isolation for 24 hours from the beginning of antibiotic therapy

IV Fluids

Replace volume as needed; with septic shock, large volumes of crystalloid may be required.

ONGOING CARE

PATIENT EDUCATION

Educate family and close contacts regarding the risk of contracting meningococcal infections.

PROGNOSIS

Overall mortality is 13%.

COMPLICATIONS

  • DIC
  • Acute tubular necrosis
  • Neurologic: sensorineural hearing loss, cranial nerve palsy, seizures
  • Obstructive hydrocephalus
  • Subdural effusions
  • Acute adrenal hemorrhage
  • Waterhouse-Friderichsen syndrome

REFERENCES

11 Centers for Disease Control and Prevention. Factsheet: meningococcal disease and meningococcal vaccine. http://www.cdc.gov/meningococcal/clinical-info.html. Accessed 2014.22 Gardner P. Clinical practice. Prevention of meningococcal disease. N Engl J Med. 2006;355(14):1466 " 1473.33 Folaranmi T, Rubin L, Martin SW, et al. Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(22):608 " 612.44 Rodr guez CL, Octavio JG, Isea C, et al. Acute polyarthritis as sole manifestation of meningococcal disease. J Clin Rheumatol. 2012;18(1):42 " 43.55 Thompson MJ, Ninis N, Perera R, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006;367(9508):397 " 403.66 Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267 " 1284.77 Fraser A, Gafter-Gvili A, Paul M, et al. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2005;(1):CD004785.

ADDITIONAL READING

  • Visintin C, Mugglestone MA, Fields EJ, et al. Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ. 2010;340:c3209.
  • Wright C, Wordsworth R, Glennie L. Counting the cost of meningococcal disease: scenarios of severe meningitis and septicemia. Paediatr Drugs. 2013;15(1):49 " 58.

CODES

ICD10

  • A39.4 Meningococcemia, unspecified
  • A39.0 Meningococcal meningitis
  • A39.2 Acute meningococcemia
  • A39.9 Meningococcal infection, unspecified
  • A39.3 Chronic meningococcemia
  • A39.89 Other meningococcal infections
  • A39.1 Waterhouse-Friderichsen syndrome

ICD9

  • 036.2 Meningococcemia
  • 036.0 Meningococcal meningitis
  • 036.89 Other specified meningococcal infections
  • 036.9 Meningococcal infection, unspecified
  • 036.3 Waterhouse-Friderichsen syndrome, meningococcal

SNOMED

  • 4089001 Meningococcemia (disorder)
  • 192644005 Meningococcal meningitis (disorder)
  • 186365005 Acute meningococcemia
  • 238425003 Meningococcal rash (disorder)

CLINICAL PEARLS

  • Invasive meningococcal disease can be rapidly fatal. Therefore, rapid identification of cases with early treatment is essential for good clinical outcomes. Treat then test in suspected cases
  • Provide chemoprophylaxis to close contacts.
  • Vaccinate at-risk populations as a preventive measure.