What antibiotics are recommended for a patient with diphtheria?

Antibiotic Treatment for Diphtheria

For active diphtheria infection, administer a 14-day course of oral erythromycin (children: 40 mg/kg/day; adults: 1 g/day) as the preferred antibiotic, combined with immediate diphtheria antitoxin administration after sensitivity testing. 1, 2

Primary Antibiotic Options

Two antibiotics are recommended for treating diphtheria:

• Erythromycin (preferred): 14-day course at 40 mg/kg/day for children or 1 g/day for adults, administered orally 1, 3
• Benzathine penicillin (alternative): Single intramuscular injection of 600,000 units for children <6 years or 1,200,000 units for those ≥6 years 4, 1

Erythromycin is slightly more effective at eliminating the organism, but benzathine penicillin offers the advantage of single-dose administration, which eliminates compliance concerns with multi-day oral regimens 4, 1. However, the 14-day erythromycin course is generally preferred because it more reliably eradicates the organism 5.

Critical Treatment Algorithm

Immediate Actions (Do Not Delay)

1. Administer diphtheria antitoxin immediately after sensitivity testing—this is the cornerstone of treatment and must not be delayed 2, 6
2. Start antibiotics simultaneously with either erythromycin or penicillin 1, 2
3. Obtain cultures before starting antibiotics, but do not wait for results to initiate treatment 4, 7

Why Antitoxin Comes First

Antitoxin neutralizes circulating toxin but cannot reverse damage already done, making early administration critical for reducing mortality from myocarditis and neuropathy 1, 8. The degree of protection is inversely proportional to illness duration before antitoxin administration 6. Even with immediate serum and antibiotic treatment, mortality remains high if antitoxin is delayed 9.

Follow-Up Culture Requirements

All patients must have follow-up cultures after completing antibiotic therapy 4, 2. This is a critical step that is often overlooked:

• If cultures remain positive: Administer an additional 10-day course of oral erythromycin 4, 1, 2
• Reculture 2 weeks after therapy completion: Studies show 21% of carriers relapse when erythromycin is given for only 6 days, emphasizing the need for the full 14-day course and follow-up cultures 5

Contact Prophylaxis (Different Regimen)

All close contacts require antimicrobial prophylaxis regardless of vaccination status 4, 1, 2:

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

Do not wait for culture results before starting prophylaxis—this could allow secondary transmission 7. Contacts should also receive throat swabs immediately and be monitored daily for 7 days 4, 7.

Common Pitfalls to Avoid

• Never delay antitoxin while waiting for culture confirmation—clinical suspicion alone warrants treatment 2, 9
• Do not use shorter antibiotic courses—the full 14-day erythromycin regimen is necessary to prevent relapse 5
• Do not skip follow-up cultures—carriers can persist despite initial treatment 4, 5
• Remember that antibiotics alone are insufficient—they halt toxin production but do not neutralize existing toxin, which is why antitoxin is essential 8, 10

Special Considerations

For cutaneous diphtheria caused by toxigenic strains, use the same antimicrobial regimen as respiratory diphtheria 1. Equine antitoxin carries a 7% risk of immediate hypersensitivity reactions and 5% risk of serum sickness, requiring sensitivity testing before administration 4, 1, 2.