What is the management and treatment of diphtheria?

Management and Treatment of Diphtheria

Immediate Life-Saving Treatment

Administer diphtheria antitoxin (DAT) immediately upon clinical suspicion without waiting for laboratory confirmation, as mortality remains very high without prompt antitoxin therapy. 1, 2

Critical First Actions (Within Hours)

• Obtain DAT from CDC Emergency Operations Center (770-488-7100) and administer after sensitivity testing for horse serum allergy. 1
• The standard dose is 100,000 international units IM for severe respiratory diphtheria with pseudomembrane and systemic toxicity. 1
• Perform skin testing for equine serum hypersensitivity before administration, as immediate reactions occur in ~7% and serum sickness in ~5% of recipients. 1
• Early antitoxin administration is critical because protection is inversely proportional to illness duration before treatment. 3

Concurrent Antibiotic Therapy

Start antibiotics simultaneously with antitoxin using either:

• Erythromycin 40 mg/kg/day (children) or 1 g/day (adults) orally for 14 days 1, 4, 5
• OR benzathine penicillin IM as single dose: 600,000 units (<6 years) or 1,200,000 units (≥6 years) 1

Erythromycin may be slightly more effective, but IM benzathine penicillin ensures compliance by avoiding multi-day oral regimens. 1

Airway Management and Supportive Care

• Monitor closely for airway compromise from pseudomembrane obstruction, severe neck swelling ("bull neck"), or laryngeal involvement requiring intubation. 1
• Bull neck appearance and extensive pseudomembrane (score >2) are associated with high mortality. 6
• Patients may develop stridor, respiratory distress, and sepsis requiring ICU-level care. 1

Monitoring for Life-Threatening Complications

Cardiac Toxicity (Most Lethal Complication)

• Myocarditis occurs in 30-68% of cases and carries 63% mortality when present. 6, 7
• Monitor with serial ECGs and cardiac enzymes for arrhythmias and heart failure. 6, 7

Neurological Complications

• Neuropathy develops in 10-15% of cases, typically presenting as cranial nerve palsies or peripheral neuropathy. 6, 7

Respiratory Compromise

• Occurs in 7-44% of cases from membrane obstruction or paralysis of respiratory muscles. 6, 7

Microbiological Confirmation and Follow-Up

• Obtain throat/nasopharyngeal cultures before starting antibiotics when possible, but never delay treatment. 1
• Perform Elek agar virulence test to confirm toxin production. 1
• Obtain first follow-up culture immediately after completing antimicrobial course, and second culture at minimum 2 weeks after therapy completion. 8

Management of Persistent Carriers

• If follow-up cultures remain positive, administer additional 10-day course of oral erythromycin (40 mg/kg/day children; 1 g/day adults) and repeat culture sequence. 1, 8, 4
• Continue this cycle until cultures are negative. 1, 8

Contact Investigation and Prophylaxis

Identification of Close Contacts

All close contacts require immediate intervention regardless of vaccination status, including:

• Household members 1
• Persons with habitual close contact 1
• Those directly exposed to oral secretions 1

Antimicrobial Prophylaxis for All Close Contacts

Administer prophylaxis immediately without awaiting culture results:

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

IM benzathine penicillin is preferred to ensure compliance. 1

Active Immunization of Contacts

• Contacts with <3 doses of diphtheria toxoid or unknown vaccination status: give immediate dose and complete primary series. 1
• Contacts with completed primary series (≥3 doses) who haven't received toxoid within 5 years: give booster dose. 1

Surveillance of Contacts

• Examine all close contacts daily for 7 days for evidence of disease. 1
• Obtain cultures from all contacts regardless of vaccination status. 1
• Contacts identified as carriers follow same treatment and culture schedule as cases. 8

Special Considerations

Cutaneous Diphtheria

• If toxigenic C. diphtheriae isolated from cutaneous lesion, investigate and treat contacts as with respiratory diphtheria. 1
• If nontoxigenic strain confirmed, routine contact investigation unnecessary. 1

C. ulcerans Infections

• Treat C. ulcerans diphtheria-like illness identically to C. diphtheriae with urgent DAT and antibiotics, as both produce diphtheria toxin causing clinically indistinguishable life-threatening disease. 1
• Human-to-human transmission not documented for C. ulcerans, so antibiotic prophylaxis of contacts not required, but update vaccination status. 1

Critical Pitfalls to Avoid

• Never wait for laboratory confirmation before administering antitoxin—clinical suspicion alone warrants immediate treatment. 1, 2
• Do not rely solely on immediate post-treatment cultures or clinical improvement to assume eradication—documented microbiological clearance at 2 weeks is mandatory. 8
• Do not use equine antitoxin prophylactically for contacts due to 7% hypersensitivity and 5% serum sickness risk without proven benefit over antimicrobial prophylaxis alone. 1
• Recognize that pseudomembrane may not be visible on routine examination and may only be seen during surgical procedures. 1
• Consider diphtheria in patients with low-grade fever and pseudomembranous pharyngitis, even in vaccinated individuals. 1