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APPENDIX A

Antimicrobial Chemoprophylaxis

Antimicrobial chemoprophylaxis of close contacts of a patient with invasive meningococcal disease is important to prevent secondary cases (Table). Close contacts include 1) household members (1), 2) child-care center contacts (2,3), and 3) anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management) in the 7 days before symptom onset. Health-care personnel should receive chemoprophylaxis if they were managing an airway or exposed to respiratory secretions of 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 (i.e., one lasting ≥8 hours) (4). The attack rate for household contacts exposed to patients who have sporadic meningococcal disease was estimated to be four cases/1,000 persons exposed, which is 500–800 times greater than the rate for the total population (5). In the United Kingdom, the attack rate among health-care personnel exposed to patients with meningococcal disease was 25 times higher than among the general population (6).

Chemoprophylaxis is not recommended for close contacts of patients with evidence of Neisseria meningitidis only in nonsterile sites such as an oropharyngeal swab, endotracheal secretions, or conjunctival swab. Reports of secondary cases after close contact to persons with noninvasive pneumonia or conjunctivitis are rare; there is no evidence of substantive excess risk (7–9). Furthermore, there is no indication to treat persons who are asymptomatic nasopharyngeal carriers.

Because the rate of secondary disease for close contacts is highest immediately after onset of disease in the index patient, antimicrobial chemoprophylaxis should be administered as soon as possible (ideally <24 hours after identification of the index patient). Conversely, chemoprophylaxis administered >14 days after exposure to the index patient is probably of limited or no value. Oropharyngeal or nasopharyngeal cultures are not helpful in determining the need for chemoprophylaxis and might delay institution of this preventive measure unnecessarily.

Rifampin, ciprofloxacin, and ceftriaxone are 90%–95% effective in reducing nasopharyngeal carriage of N. meningitidis and are all acceptable antimicrobial agents for chemoprophylaxis (10–13). Although sporadic resistance to rifampin and ciprofloxacin have been reported worldwide, meningococcal resistance to chemoprophylaxis antibiotics remains rare in the United States. Clinicians should report suspected chemoprophylaxis failures to their public health departments. Systemic antimicrobial therapy of meningococcal disease with agents other than ceftriaxone or other third-generation cephalosporins might not eradicate nasopharyngeal carriage of N. meningitidis reliably. If other agents have been used for treatment, the index patient should receive chemoprophylactic antibiotics for eradication of nasopharyngeal carriage before being discharged from the hospital (14).

Although azithromycin is not recommended for use as a first-line chemoprophylaxis agent, one study has reported that a single 500-mg oral dose of azithromycin was effective in eradicating nasopharyngeal carriage of N. meningitidis (15). Azithromycin, in addition to being safe and easy to administer, is also available in a suspension form and is approved for use among children. Azithromycin has been recommended for prophylaxis in the rare circumstance of sustained ciprofloxacin resistance in a local community; however, further evaluation is warranted of both the effectiveness of azithromycin in eradicating carriage of N. meningitidis and potential for development of microbial resistance (15).

References

  1. De Wals P, Hertoghe, L, Borlee-Grimee I, et al. Meningococcal disease in Belgium, secondary attach rate among household, day-care nursery and preelementary school contacts. J Infect 1981;3(Suppl 1):53–61.
  2. Jacobson JA FG, Holloway JT. Meningococcal disease in day-care centers. Pediatrics 1977;59:299–300.
  3. CDC. Exposure to patients with meningococcal disease on aircrafts—United States, 1999–2001. MMWR 2001;50:485–9.
  4. Anonymous. Meningococcal disease. Secondary attack rate and chemoprophylaxis in the United States, 1974. JAMA 1976;235:261–5.
  5. Gilmore A, Stuart J, Andrews N. Risk of secondary meningococcal disease in health-care workers. The Lancet 2000;356(9242):1654–5.
  6. Winstead JM, McKinsey DS, Tasker S, De Groote MA, Baddour LM. Meningococcal pneumonia: characterization and review of cases seen over the past 25 years. Clin Infect Dis 2000;30:87–94.
  7. Barquet N, Gasser I, Domingo P, Moraga FA, Macaya A, Elcuaz R. Primary meningococcal conjunctivitis: report of 21 patients and review. Rev Infect Dis 1990;12:838–47.
  8. Stansfield RE, Masterton RG, Dale BA, Fallon RJ. Primary meningococcal conjunctivitis and the need for prophylaxis in close contacts. J Infect 1994;29:211–4.
  9. Dworzack DL, Sanders CC, Horowitz EA, et al. Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers. Antimicrob Agents Chem 1988;32:1740–1.
  10. Schwartz B, Al-Tobaiqi A, Al-Ruwais A, et al. Comparative efficacy of ceftriaxone and rifampin in eradicating pharyngeal carriage of group A Neisseria meningitidis. Lancet 1988;2:1239–42.
  11. Gaunt P, Lambert B. Single dose ciprofloxacin for the eradication of pharyngeal carriage of Neisseria menigitidis. J Antimicrob Chemo 1988;21:489–96.
  12. Broome CV. The carrier state: Neisseria meningitidis. J Antimicrob Chem 1986;18 (Suppl A):25–34.
  13. Abramson JS SJ. Persistence of Neisseria meningitidis in the upper respiratory tract after intravenous antibiotic threrapy for systemic meningococcal disease. J Infect Dis 1985;151:370–1.
  14. Girgis N, Sultan Y, Frenck RW Jr, El-Gendy A, Farid Z, Mateczun A. Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis. Pediatr Infect Dis J 1998;17:816–9.
  15. Wu HM, Harcourt BH, Hatcher CP, et al. Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America. N Engl J Med 2009;360:886–92.

TABLE. Recommended chemoprophylaxis regimens for protection against meningococcal disease — Advisory Committee on Immunization Practices (ACIP), United States, 2012

Drug

Age group

Dosage

Duration and route of administration*

Rifampin

Children aged <1 mo

5 mg/kg every 12 hrs

2 days

Children aged ≥1 mo

10 mg/kg every 12 hrs

2 days

Adults

600 mg every 12 hrs

2 days

Ciprofloxacin§

Adults

500 mg

Single dose

Ceftriaxone

Children age <15 yrs

125 mg

Single IM dose

Ceftriaxone

Adults

250 mg

Single IM dose

Abbreviation: IM = intramuscular.

* Oral administration unless indicated otherwise.

Rifampin is not recommended for pregnant women because the drug is teratogenic in laboratory animals. Because the reliability of oral contraceptives might be affected by rifampin therapy, consideration should be given to using alternative contraceptive measures while rifampin is being administered.

§ Ciprofloxacin is not generally recommended for persons aged <18 years or for pregnant and lactating women because the drug causes cartilage damage for immature laboratory animals. However, ciprofloxacin may be used for chemoprophylaxis of children when no acceptable alternative therapy is available. A recent review identified no reports of irreversible cartilage toxicity or age-associated adverse events in children and adolescents (Source: Burstein GR, Berman SM, Blumer JL, Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis 2002;35:S191–9).


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