What prophylaxis (antibiotic chemoprophylaxis and diphtheria toxoid vaccination) is recommended for individuals with close exposure to a confirmed case of diphtheria?

Diphtheria Post-Exposure Prophylaxis

All close contacts of a confirmed or suspected diphtheria case must receive immediate antimicrobial prophylaxis (benzathine penicillin IM or erythromycin for 7-10 days) combined with diphtheria toxoid vaccination based on their immunization history, regardless of their current vaccination status. 1

Immediate Actions for All Close Contacts

Close contacts are defined as household members, persons with habitual close contact with the patient, and anyone directly exposed to the patient's oral secretions. 2

Step 1: Antimicrobial Prophylaxis (Start Immediately)

Do not wait for culture results before starting antibiotics. 2, 1 Choose one of the following regimens:

• Benzathine penicillin G (preferred for compliance): 2

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

• Oral erythromycin (may be slightly more effective): 2

  • Children: 40 mg/kg/day for 7-10 days
  • Adults: 1 g/day for 7-10 days

Benzathine penicillin is preferred because it ensures compliance with a single injection, avoiding the risk of incomplete oral antibiotic courses. 2 However, erythromycin may be marginally more effective at eradicating the organism. 2

Step 2: Obtain Cultures

Obtain nasopharyngeal and throat cultures from all close contacts before starting antibiotics, but do not delay prophylaxis while awaiting results. 2 These cultures help support the diagnosis if the index patient's cultures are negative due to prior antibiotic use. 2

Step 3: Active Immunization (Diphtheria Toxoid)

Vaccination requirements depend on the contact's immunization history: 2, 1

For contacts with <3 doses or unknown vaccination status:

• Give an immediate dose of age-appropriate diphtheria toxoid-containing vaccine (DTP, DTaP, DT for children <7 years; Td or Tdap for persons ≥7 years) 2, 3
• Complete the primary 3-dose series according to standard schedule 2, 1

For contacts with ≥3 documented doses:

• Give a booster dose if the last dose was >5 years ago 2, 1
• The 5-year interval is specifically recommended for post-exposure situations, which is shorter than the routine 10-year booster interval 1

Step 4: Daily Surveillance

Examine all contacts daily for 7 days, monitoring for pharyngeal symptoms, fever, and membrane formation. 2, 1

Follow-Up for Identified Carriers

If cultures identify a carrier of C. diphtheriae: 2

• Obtain follow-up cultures after completing antimicrobial therapy
• If cultures remain positive after either penicillin or erythromycin, administer an additional 10-day course of oral erythromycin 2
• Repeat follow-up cultures after the second course 2

Critical Clinical Pearls

Vaccination status does NOT exempt contacts from antimicrobial prophylaxis—even fully vaccinated individuals require antibiotics. 1 This is because vaccination protects against toxin-mediated disease but does not prevent colonization or transmission of the organism. 2

Passive immunization with equine diphtheria antitoxin is NOT generally recommended for contacts due to significant risks: 7% experience immediate hypersensitivity reactions and 5% develop serum sickness. 2 The risk of adverse reactions outweighs the minimal benefit when antimicrobial prophylaxis is provided. 2 If antitoxin is considered (only in exceptional circumstances with impossible surveillance), use 5,000-10,000 units IM after sensitivity testing at a site different from the toxoid injection. 2

Special Populations

Immunocompromised contacts require more aggressive surveillance, completion of the full antimicrobial prophylaxis course, and vaccination according to immunocompromised vaccination schedules. 1

Pregnant women can safely receive Td vaccine, though waiting until the second trimester is a reasonable precaution to minimize theoretical concerns. 2 Antimicrobial prophylaxis should not be delayed. 2

Cutaneous Diphtheria Considerations

If the index case has cutaneous diphtheria caused by a toxigenic strain, investigate and provide prophylaxis to contacts exactly as described above. 2 If the strain is confirmed nontoxigenic, routine investigation or prophylaxis of contacts is not necessary. 2