Drug of Choice for Pertussis
Azithromycin is the drug of choice for treating pertussis across all age groups, with superior tolerability and compliance compared to erythromycin while maintaining equivalent bacteriologic efficacy. 1
First-Line Treatment Recommendations
Infants and Children
- For infants <1 month: Azithromycin is specifically preferred due to significantly lower risk of infantile hypertrophic pyloric stenosis (IHPS) compared to erythromycin 1, 2
- For infants 1-5 months: Both azithromycin and clarithromycin are recommended as first-line agents based on effectiveness, safety, and convenient dosing 1
- For infants ≥6 months and children: Azithromycin 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg/day (maximum 250 mg) on days 2-5 1
Adults
- Azithromycin 500 mg on day 1, followed by 250 mg daily on days 2-5 1
Comparative Evidence Supporting Azithromycin
The superiority of azithromycin over erythromycin is well-established:
- Equivalent efficacy: A large multicenter randomized trial demonstrated 100% bacterial eradication with both azithromycin and erythromycin, with no bacterial recurrence in either group 3
- Superior tolerability: Gastrointestinal adverse events occurred in only 18.8% of azithromycin recipients versus 41.2% with erythromycin, including significantly less nausea (2.9% vs 8.4%), vomiting (5.0% vs 13.0%), and diarrhea (7.1% vs 11.8%) 3
- Markedly better compliance: 90% of patients completed the full azithromycin course versus only 55% with erythromycin 3. In outbreak settings, completion rates were 93% with azithromycin versus 57% with erythromycin 4
Alternative Treatment Options
- For patients >2 months with macrolide contraindications: Trimethoprim-sulfamethoxazole (TMP-SMZ) is the recommended alternative 1, 5
- Erythromycin should only be used when azithromycin is unavailable 6, with dosing of 40-50 mg/kg/day in 4 divided doses for 14 days in children, or 2 g/day in 4 divided doses for 14 days in adults 6, 7
Critical Timing Considerations
- Start antibiotics immediately upon clinical suspicion without waiting for culture confirmation 1
- Early treatment (catarrhal phase, first 2 weeks) is critical: Antibiotics administered early rapidly clear B. pertussis from the nasopharynx, decrease coughing paroxysms, and reduce complications 1
- Late treatment (paroxysmal phase, >3 weeks) has limited clinical benefit but remains indicated to prevent transmission 1
Important Safety Warnings
Erythromycin-Specific Risks
- IHPS risk in neonates: Erythromycin carries increased risk of infantile hypertrophic pyloric stenosis, particularly in infants <3 weeks old (7 cases out of 157 exposed infants versus 0 out of 125 unexposed) 6
- Drug interactions: Erythromycin is a potent CYP3A inhibitor and is contraindicated with astemizole, cisapride, pimazole, or terfenadine due to risk of QT prolongation, cardiac arrest, and torsades de pointes 6
Azithromycin Administration
- Do not administer simultaneously with aluminum- or magnesium-containing antacids as they reduce absorption 1
- Use with caution in patients with impaired hepatic function 1
Infection Control Measures
- Isolate patients at home and away from work/school for 5 days after starting antibiotics to prevent transmission 1
- Postexposure prophylaxis: Use the same antimicrobial regimens and dosing as for treatment 1
- Prioritize prophylaxis for: All close contacts, especially infants <12 months and women in third trimester of pregnancy 1
Common Pitfalls to Avoid
- Do not delay treatment waiting for diagnostic confirmation - start immediately on clinical suspicion 1
- Do not use erythromycin in infants <1 month unless azithromycin is unavailable, and if used, parents must be counseled about IHPS signs 6
- Do not expect clinical benefit from antibiotics if started during paroxysmal phase - the primary goal becomes preventing transmission 1
- Do not use β-agonists, antihistamines, corticosteroids, or pertussis immunoglobulin - these have no proven benefit in controlling coughing paroxysms 1