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Penicillin vs. erythromycin in the treatment of diphtheria
1Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam.
Insights
Penicillin therapy for diphtheria in Vietnamese children cleared fever faster than erythromycin. However, some isolates showed erythromycin resistance, supporting penicillin as the preferred first-line treatment.
Area of Science:
- Infectious Diseases
- Pediatrics
- Pharmacology
Background:
- Diphtheria remains a significant public health concern, particularly in resource-limited settings.
- Effective antibiotic therapy is crucial for reducing transmission and improving patient outcomes.
- Understanding treatment efficacy and resistance patterns is vital for guiding clinical practice.
Purpose of the Study:
- To compare the efficacy of penicillin versus erythromycin in treating diphtheria in Vietnamese children.
- To assess bacteriologic and clinical clearance rates, including fever resolution.
- To investigate antimicrobial resistance patterns of *Corynebacterium diphtheriae* isolates.
Main Methods:
- An open-label, randomized trial involving 86 Vietnamese children diagnosed with diphtheria.
- Participants were assigned to receive either intramuscular and oral penicillin or oral erythromycin for specified durations.
- Clinical outcomes (membrane and fever clearance) and bacteriologic clearance were monitored. Antimicrobial susceptibility testing was performed on isolates.
Main Results:
- No significant differences were observed in membrane or bacteriologic clearance times between the two treatment groups.
- Median time to fever clearance was significantly shorter in the penicillin group (27 hours) compared to the erythromycin group (46 hours) (P = .0004).
- A notable proportion (27%) of *Corynebacterium diphtheriae* isolates were resistant to erythromycin, while all isolates remained susceptible to penicillin. Treatment failures and relapses occurred in the penicillin group, alongside three cases of diphtheritic myocarditis.
Conclusions:
- Penicillin demonstrates a faster fever clearance rate compared to erythromycin in pediatric diphtheria patients in Vietnam.
- The emergence of erythromycin-resistant *Corynebacterium diphtheriae* strains necessitates careful consideration of treatment options.
- Penicillin is recommended as the first-line antibiotic therapy for diphtheria in this population due to its consistent efficacy and susceptibility of isolates.
Abstract:
In an open-label, randomized trial, 44 Vietnamese children with diphtheria were given penicillin therapy (intramuscular benzylpenicillin, 50,000 U/[kg.d] for 5 days and then oral penicillin, 50 mg/[kg.d] for 5 days), and 42 were given erythromycin therapy (50 mg/[kg.d] orally for 10 days). There were no differences in times to membrane clearance or bacteriologic clearance, but median times to fever clearance were 27 hours (95% confidence interval [CI], 19-30; range, 0-124 hours) for penicillin recipients and 46 hours (95% CI, 34-54; range, 0-148 hours) for erythromycin recipients (P = .0004). In the penicillin group, acute treatment failed for one patient, and one patient relapsed. Three patients in the penicillin group developed diphtheritic myocarditis as evidenced by abnormal electrocardiograms. Erythromycin did not cause prolongation of the QT interval corrected for heart rate. Cultures of specimens from 15 patients (17.4%) were positive for toxigenic Corynebacterium diphtheriae. All isolates were susceptible to penicillin, but for isolates (27%), all of which were from patients who received penicillin treatment, were resistant to erythromycin (minimum inhibitory concentrations, > 64 mg/L). Penicillin is recommended as first-line treatment for diphtheria in Vietnam.