Diphtheria Antibiotic Treatment
For active diphtheria infection, administer a 14-day course of erythromycin (children: 40 mg/kg/day divided; adults: 1 g/day) as the preferred antibiotic, or alternatively benzathine penicillin G as a single intramuscular dose (600,000 units for children <6 years; 1,200,000 units for ≥6 years), always in conjunction with diphtheria antitoxin. 1
Primary Antibiotic Regimen
Erythromycin is the first-line choice for treating diphtheria because it may be slightly more effective at eliminating Corynebacterium diphtheriae from the nasopharynx and preventing the carrier state. 2, 1
Dosing for Active Infection:
- Children: Erythromycin 40 mg/kg/day orally for 14 days 1
- Adults: Erythromycin 1 g/day orally for 14 days 1
- Alternative: Benzathine penicillin G IM single dose (600,000 units if <6 years; 1,200,000 units if ≥6 years) 2
Penicillin Alternative:
Penicillin G can be used when compliance with multi-day oral therapy is a concern, as the single intramuscular injection eliminates adherence issues. 2 However, a Vietnamese study found penicillin resulted in faster fever clearance (median 27 hours vs 46 hours, P=0.0004) but identified emerging erythromycin resistance in 27% of isolates from penicillin-treated patients. 3
For hospitalized patients with severe disease, intravenous penicillin G at 2-3 million units/day in divided doses for 10-12 days is recommended as adjunctive therapy to antitoxin. 4
Critical Treatment Principles
Antitoxin Administration is Mandatory:
Antibiotics alone are insufficient—diphtheria antitoxin must be administered promptly to neutralize circulating toxin, though it cannot reverse damage already done. 1 Sensitivity testing for equine antitoxin is required due to 7% risk of immediate hypersensitivity and 5% risk of serum sickness. 2, 1
Treatment Duration Matters:
The full 14-day course is essential for eradicating the organism and preventing the carrier state. 1 Shorter courses risk treatment failure and persistent carriage.
Post-Treatment Monitoring
Follow-up cultures are mandatory to confirm bacterial eradication:
- Obtain first culture immediately after completing antimicrobial therapy 5
- Obtain second culture at minimum 2 weeks after therapy completion 5
If cultures remain positive: Administer an additional 10-day course of oral erythromycin (children: 40 mg/kg/day; adults: 1 g/day) and repeat the culture sequence. 2, 5
Contact Prophylaxis
All close contacts require immediate antimicrobial prophylaxis regardless of vaccination status, without waiting for culture results. 2, 6
Prophylaxis Options:
- Erythromycin: 7-10 days orally (children: 40 mg/kg/day; adults: 1 g/day) 2
- Benzathine penicillin G: Single IM dose (600,000 units if <6 years; 1,200,000 units if ≥6 years) 2
Erythromycin may be slightly more effective for prophylaxis, but benzathine penicillin ensures compliance with single-dose administration. 2
Monitor contacts daily for 7 days for evidence of disease development. 2, 6
Common Pitfalls to Avoid
- Never delay antitoxin administration while waiting for culture confirmation—clinical suspicion warrants immediate treatment 1
- Do not use antibiotics alone without antitoxin, as antibiotics only stop toxin production but cannot neutralize existing toxin 7
- Do not skip follow-up cultures—asymptomatic carriage can persist despite clinical improvement, creating ongoing transmission risk 5
- Do not assume eradication based on symptom resolution alone—documented microbiological clearance is essential 5
Special Considerations
Cutaneous Diphtheria:
If caused by toxigenic strains, use the same antimicrobial regimen as respiratory diphtheria. 1 Investigation and prophylaxis of contacts should proceed identically to respiratory cases. 2
Emerging Resistance:
Recent data show 4% of C. diphtheriae isolates have MICs higher than wild-type for erythromycin, though phenotypically detectable resistance remains rare. 8 One Vietnamese study found 27% erythromycin resistance among isolates. 3 This supports using penicillin when local resistance patterns suggest erythromycin may be compromised.