What is the treatment for Corynebacterium diphtheriae infection?

Treatment of Corynebacterium diphtheriae Infection

Immediate administration of diphtheria antitoxin (DAT) is the critical first-line treatment for suspected respiratory diphtheria caused by Corynebacterium diphtheriae, and must be given urgently without waiting for laboratory confirmation, followed by appropriate antibiotic therapy. 1

Immediate Management Algorithm

Step 1: Antitoxin Administration (Most Critical)

• Administer diphtheria antitoxin (DAT) immediately if respiratory diphtheria is suspected - this is the single most important intervention to prevent mortality from toxin-mediated complications including myocarditis and neuropathy 1
• Do not wait for culture confirmation before giving DAT, as delays increase risk of cardiac and neurologic complications 1
• DAT neutralizes circulating toxin but cannot reverse toxin already bound to tissues 1
• Contact CDC for DAT availability, as it is not routinely stocked in most facilities 2

Step 2: Antibiotic Therapy

• Erythromycin is FDA-approved as an adjunct to antitoxin for C. diphtheriae infections to eradicate the organism and prevent carrier state 3
• Antibiotics eliminate the organism but do not neutralize toxin - they are adjunctive to antitoxin, not a substitute 1, 3
• For severe infections or multidrug-resistant strains, vancomycin is recommended as first-line therapy 1
• Azithromycin has been used successfully in case reports, particularly for C. ulcerans 1

Step 3: Supportive Care and Monitoring

• Monitor closely for airway obstruction from pseudomembrane extension into the trachea-bronchial tree 4
• Cardiac monitoring is essential due to risk of toxin-mediated myocarditis 4
• Neurologic assessment for toxin-mediated neuropathy 4

Treatment for Specific Clinical Scenarios

Respiratory Diphtheria (Classic Presentation)

• Gray adherent pseudomembrane on tonsils, pharynx, or nose with sore throat and low-grade fever 4
• DAT must be given first, followed by erythromycin 1, 3
• Treatment duration: 10-14 days of antibiotics 3

C. ulcerans Infections

• Follow the same treatment guidelines as for C. diphtheriae 1
• These infections are clinically indistinguishable from classic diphtheria 2
• Five cases of toxigenic C. ulcerans respiratory illness were identified in the U.S. from 1996-2018 2

Non-toxigenic Strains

• Even non-toxigenic C. diphtheriae can cause invasive disease 5
• Antibiotic therapy is still indicated to eradicate the organism 3
• DAT is not necessary for confirmed non-toxigenic strains, but if toxigenicity is unknown, treat as toxigenic until proven otherwise 1

Carrier State Eradication

• Erythromycin is effective in eliminating the organism from carriers 3
• This prevents transmission and establishment of new carriers 3

Critical Pitfalls to Avoid

Common Error #1: Delaying antitoxin while awaiting culture results

• This is the most dangerous mistake - DAT must be given on clinical suspicion alone 1
• From 1996-2018, only 14 respiratory diphtheria cases were reported in the U.S., with declining DAT requests (average 3 per year from 2008-2018) 2
• Low clinical suspicion due to rarity can lead to delayed diagnosis and treatment 2

Common Error #2: Treating with antibiotics alone

• Antibiotics do not neutralize circulating toxin 1
• Toxin-mediated complications (myocarditis, neuropathy) cause mortality, not the bacterial infection itself 4

Common Error #3: Dismissing Corynebacterium as a contaminant

• Non-toxigenic strains can cause invasive disease, particularly in immunocompromised patients 5
• Always obtain species identification and toxin testing 1

Contact Management and Prevention

Close Contacts

• Assess vaccination status of all close contacts 1
• Update vaccinations as needed with diphtheria-toxoid-containing vaccine 1
• Adults should receive Td or Tdap boosters every 10 years after completing primary childhood vaccination 1

Vaccination Status and Risk

• Unvaccinated or inadequately vaccinated individuals are at highest risk for severe disease 4
• Many U.S. adults lack protective immunity: 22-62% of adults 18-39 years and 41-84% of those ≥60 years may lack protective antitoxin levels 6

Special Populations

Pregnant Women

• Tetanus toxoid vaccine is recommended during pregnancy for previously unvaccinated women 6
• This provides passive protection to the infant 6

Patients with Comorbidities

• A case of C. diphtheriae biovar Belfanti was reported in a patient with rheumatoid arthritis, demonstrating risk in immunocompromised hosts 5
• Bacteremia with toxigenic C. diphtheriae occurred in a burn patient, resulting in death despite treatment 7