What are the post-exposure prophylaxis recommendations for an individual exposed to diphtheria, particularly if they are not up-to-date with their diphtheria toxoid-containing vaccine (Td or Tdap) vaccinations or have a weakened immune system?

Diphtheria Post-Exposure Prophylaxis

Immediate Management for All Close Contacts

All close contacts of a confirmed or suspected diphtheria patient must receive immediate antimicrobial prophylaxis regardless of vaccination status, combined with urgent vaccination assessment and daily surveillance for 7 days. 1

Close contacts include household members, persons with habitual close contact with the patient, and anyone directly exposed to the patient's oral secretions. 1

Antimicrobial Prophylaxis (Required for ALL Contacts)

Administer antimicrobial prophylaxis immediately without waiting for culture results. 1 Choose one of the following regimens:

• Benzathine penicillin G intramuscularly (preferred for compliance): 1

  • Children <6 years: 600,000 units IM as single dose 1
  • Persons ≥6 years: 1,200,000 units IM as single dose 1

• Oral erythromycin for 7-10 days (slightly more effective): 1, 2

  • Children: 40 mg/kg/day divided doses 1, 2
  • Adults: 1 g/day divided doses 1, 2

Benzathine penicillin is preferred because it ensures compliance with a single injection, avoiding the risk of incomplete oral therapy. 1

Culture Collection and Follow-Up

• Obtain nasopharyngeal and throat cultures from all close contacts before starting antimicrobial prophylaxis (but do not delay treatment). 1
• Identified carriers who remain culture-positive after completing initial antimicrobial therapy require an additional 10-day course of oral erythromycin with repeat follow-up cultures. 1, 3
• Monitor all contacts daily for 7 days for signs of disease development (sore throat, fever, malaise, pharyngeal membrane). 1

Active Immunization Based on Vaccination History

Contacts with <3 Doses or Unknown Vaccination Status

Administer an immediate dose of age-appropriate diphtheria toxoid-containing vaccine and complete the primary 3-dose series according to schedule. 1

• First dose: Immediate administration 1
• Second dose: ≥4 weeks after first dose 1
• Third dose: 6-12 months after second dose 1

Contacts with ≥3 Documented Doses

Administer a booster dose of diphtheria toxoid-containing vaccine if the last dose was >5 years ago. 1

• Adults ≥11 years: Tdap preferred if not previously received; otherwise Td 1
• Children <7 years: DTaP 1
• Children 7-10 years: Tdap or Td 1

The 5-year interval for post-exposure boosting differs from the routine 10-year booster schedule and reflects the high-risk exposure situation. 1

Passive Immunization (Generally NOT Recommended)

Equine diphtheria antitoxin is NOT routinely recommended for post-exposure prophylaxis due to significant risks of adverse reactions. 1

• Immediate hypersensitivity reactions occur in approximately 7% of recipients 1
• Serum sickness develops in approximately 5% of recipients 1
• No evidence supports additional benefit beyond antimicrobial prophylaxis 1

If antitoxin is deemed necessary (e.g., unvaccinated contact with impossible surveillance): 1

• Perform sensitivity testing before administration 1
• Administer 5,000-10,000 units IM at a site different from toxoid injection 1
• The risk-benefit calculation must weigh the small risk of secondary disease against the substantial risk of equine antitoxin reactions 1

Special Considerations for Immunocompromised Contacts

While the guidelines do not explicitly address immunocompromised contacts, general medical principles suggest these individuals warrant:

• More aggressive surveillance with lower threshold for antitoxin administration
• Completion of full antimicrobial prophylaxis course
• Vaccination according to immunocompromised vaccination schedules
• Consider serologic testing to verify adequate antibody response 1

Critical Clinical Pearls

• Do not delay antimicrobial prophylaxis while awaiting culture results - immediate treatment prevents secondary transmission. 1
• Vaccination status does not exempt contacts from antimicrobial prophylaxis - even fully vaccinated individuals require antibiotics. 1
• The 5-year booster interval for exposed contacts differs from routine 10-year intervals - this is a common source of error. 1
• Erythromycin is the preferred antibiotic for carriers who remain culture-positive after initial penicillin treatment. 1
• Daily clinical surveillance for 7 days is mandatory - watch for pharyngeal symptoms, fever, and membrane formation. 1