What is the recommended treatment for pertussis (whooping cough)?

Treatment of Pertussis (Whooping Cough)

Azithromycin is the first-line antibiotic for treating pertussis across all age groups, with a 5-day course being as effective as 14 days of erythromycin while causing significantly fewer side effects. 1

First-Line Antibiotic Therapy

Azithromycin Dosing by Age

Infants < 1 month:

• 10 mg/kg per day for 5 days 1
• Azithromycin is specifically preferred in this age group due to significantly lower risk of infantile hypertrophic pyloric stenosis (IHPS) compared to erythromycin 1, 2

Infants 1-5 months:

• 10 mg/kg per day for 5 days 1
• Both azithromycin and clarithromycin are acceptable first-line options 1

Infants ≥ 6 months, children, and adolescents:

• 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg per day (maximum 250 mg) on days 2-5 1

Adults:

• 500 mg on day 1, followed by 250 mg per day on days 2-5 1

Important administration note: Do not give azithromycin simultaneously with aluminum- or magnesium-containing antacids as they reduce absorption 1

Alternative First-Line Options

Clarithromycin is equally effective as azithromycin and erythromycin for pertussis treatment, with a 7-day course demonstrating equivalent microbiological eradication 1, 3, 4. This represents a reasonable alternative when azithromycin is unavailable, particularly for infants 1-5 months of age 1.

Second-Line Therapy

For patients > 2 months with macrolide contraindications or allergies:

• Trimethoprim-sulfamethoxazole (TMP-SMZ) is the recommended alternative 1
• This is particularly important for patients with documented hypersensitivity to any macrolide agent 1

Erythromycin: When and How to Use

Erythromycin should only be used when azithromycin is unavailable 5, with the following critical considerations:

Dosing:

• Children: 40-50 mg/kg/day in 4 divided doses for 14 days 5, 6
• Adults: 2 g/day in 4 divided doses for 14 days 5, 6

Critical safety warning for neonates:

• Erythromycin carries increased risk of IHPS, particularly in infants < 3 weeks old, with 7 cases out of 157 exposed infants versus 0 cases out of 125 unexposed infants 5
• Parents must be counseled about IHPS signs (projectile vomiting, visible peristaltic waves) if erythromycin is prescribed to newborns 5
• Infants receiving erythromycin must be monitored for IHPS development 5

Drug interactions:

• Erythromycin is a potent inhibitor of cytochrome P450 enzyme system (CYP3A subclass) 5, 2
• Contraindicated with astemizole, cisapride, pimazole, or terfenadine due to risk of QT prolongation, cardiac arrest, and torsades de pointes 5, 2

Tolerability issues:

• Gastrointestinal side effects are significantly more frequent and severe with erythromycin compared to azithromycin (41.2% vs 18.8%) 7
• Compliance is markedly worse: only 55% of patients took 100% of prescribed erythromycin doses versus 90% with azithromycin 7

Timing of Treatment: Critical for Effectiveness

Start antibiotics immediately upon clinical suspicion without waiting for culture confirmation 1. The effectiveness of treatment depends critically on when it is initiated:

Early treatment (catarrhal phase, first 2 weeks):

• Rapidly clears B. pertussis from the nasopharynx 1
• Decreases coughing paroxysms and reduces complications 1
• Reduces duration and severity of symptoms 1

Late treatment (paroxysmal phase, > 3 weeks):

• Has limited clinical benefit for the patient 1
• Still indicated to prevent transmission to others 1
• Approximately 80-90% of untreated patients will spontaneously clear B. pertussis within 3-4 weeks from cough onset 1

Isolation Requirements

Isolate patients at home and away from work/school for 5 days after starting antibiotics 1. This is essential because pertussis is highly contagious with a secondary attack rate exceeding 80% among susceptible persons 1.

Postexposure Prophylaxis

Use the same antimicrobial agents and dosing regimens for prophylaxis as for treatment 1. Prophylaxis should be administered to close contacts within 21 days of exposure, with priority given to:

• Infants < 12 months of age 1
• Women in the third trimester of pregnancy 1
• All household contacts 1
• Healthcare workers with known exposure 1

What Does NOT Work

The following therapies have no significant benefit in controlling coughing paroxysms and should not be used: 1

• Long-acting β-agonists
• Antihistamines
• Corticosteroids
• Pertussis immunoglobulin

Comparative Efficacy Evidence

The evidence strongly supports azithromycin as the optimal choice. A large multicenter randomized trial demonstrated 100% bacterial eradication with both azithromycin (5 days) and erythromycin (14 days), with no bacterial recurrence in either group 7. However, azithromycin demonstrated superior tolerability with significantly fewer gastrointestinal adverse events (18.8% vs 41.2%) and markedly better compliance (90% vs 55% taking 100% of prescribed doses) 7. A Cochrane systematic review confirmed that short-term antibiotics (azithromycin for 3 days, clarithromycin for 7 days) were equally effective as 14-day erythromycin regimens for microbiological eradication, with fewer side effects 4.