What is the recommended treatment for a patient with diphtheria?

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Last updated: February 1, 2026View editorial policy

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Diphtheria Treatment

Immediate administration of diphtheria antitoxin combined with a 14-day course of erythromycin (40 mg/kg/day in children; 1g/day in adults) is the definitive treatment for active diphtheria infection, with antitoxin being critical to prevent mortality from toxin-mediated complications. 1, 2

Critical First Actions

Antitoxin must be given immediately upon clinical suspicion—do not wait for culture confirmation. 1, 2, 3 The antitoxin neutralizes circulating toxin but cannot reverse damage already done, making early administration the single most important determinant of survival. 1 Delayed antitoxin administration is associated with high mortality even with appropriate antibiotic therapy. 3

Antitoxin Administration Protocol

  • Perform sensitivity testing before administering equine diphtheria antitoxin due to 7% risk of immediate hypersensitivity reactions and 5% risk of serum sickness. 4, 1
  • Dosing: 5,000-10,000 units IM at a site different from toxoid injection. 4, 2
  • Antitoxin can be obtained from manufacturers (Connaught Labs, Inc., or Sclavo, Inc.) or the CDC Division of Immunization (telephone: 404-639-2888). 4

Antimicrobial Therapy

Erythromycin is the preferred antibiotic for eliminating the organism and preventing toxin production. 1, 2

Antibiotic Options

  • First-line: Oral erythromycin for 14 days

    • Children: 40 mg/kg/day in divided doses 4, 1
    • Adults: 1g/day in divided doses 4, 1
    • Erythromycin is slightly more effective at organism eradication than penicillin 4, 1
  • Alternative: Benzathine penicillin G as single IM injection

    • <6 years: 600,000 units 4, 1
    • ≥6 years: 1,200,000 units 4, 1
    • Advantage: Single-dose administration improves compliance 1

Follow-Up Culture Verification

  • Obtain follow-up cultures after completing antimicrobial therapy. 2
  • If cultures remain positive: Administer an additional 10-day course of oral erythromycin and repeat cultures. 4, 2
  • This is critical as 21% of carriers relapse after initial 6-day erythromycin courses. 5

Management of Close Contacts

All close contacts require immediate antimicrobial prophylaxis regardless of vaccination status—do not wait for culture results. 4, 2, 6

Contact Identification

Close contacts include: 4, 6

  • All household members
  • Persons with habitual close contact with the patient
  • Anyone directly exposed to oral secretions

Prophylaxis Protocol

Antimicrobial prophylaxis: 4, 6

  • Benzathine penicillin G IM (preferred for compliance): 600,000 units (<6 years) or 1,200,000 units (≥6 years) 4, 6
  • OR oral erythromycin for 7-10 days: 40 mg/kg/day (children) or 1g/day (adults) 4, 6

Active immunization: 4, 6

  • Contacts with <3 doses or unknown vaccination status: Immediate dose of age-appropriate diphtheria toxoid-containing vaccine and complete primary 3-dose series 4, 6
  • Contacts with ≥3 documented doses: Booster dose if last dose was >5 years ago 4, 6

Surveillance: 4, 6

  • Obtain cultures from all close contacts 4
  • Daily clinical examination for 7 days watching for pharyngeal symptoms, fever, and membrane formation 4, 6

Common Pitfalls to Avoid

  • Never delay antitoxin while awaiting culture results—clinical suspicion alone warrants immediate treatment. 1, 2, 3 Mortality remains very high without immediate antitoxin administration. 3
  • Do not use antibiotics alone—they eliminate the organism but do not neutralize circulating toxin. 1, 7 Antibiotics must be paired with antitoxin to limit morbidity. 7
  • Do not assume vaccinated contacts are protected from transmission—vaccination reduces transmission by only 60% and vaccinated individuals can become colonized and transmit. 7 All contacts require antimicrobial prophylaxis. 6
  • Do not use shorter antibiotic courses—14 days is required for active infection, as shorter courses (6 days) result in 21% relapse rates. 5
  • Do not skip follow-up cultures—reculture at minimum 2 weeks after therapy completion to ensure organism eradication. 4, 5

Special Considerations

Cutaneous Diphtheria

  • If toxigenic strain confirmed: Same antimicrobial regimen and contact investigation as respiratory diphtheria 4, 1
  • If nontoxigenic strain: Routine contact investigation not necessary 4

Immunocompromised Contacts

  • Warrant more aggressive surveillance, completion of full antimicrobial prophylaxis course, and vaccination according to immunocompromised schedules 6

References

Guideline

Diphtheria Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Initial Treatment for Diphtheroid Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diphtheria carriers and the effect of erythromycin therapy.

Antimicrobial agents and chemotherapy, 1974

Guideline

Diphtheria Post-Exposure Prophylaxis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Clinical and Epidemiological Aspects of Diphtheria: A Systematic Review and Pooled Analysis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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