What is the recommended antibiotic treatment and dosing for pertussis in children, adults, newborns, and for macrolide‑resistant cases, and what prophylaxis should be given to close contacts?

Antibiotic Treatment of Pertussis

First-Line Treatment: Azithromycin for All Ages

Azithromycin is the preferred first-line antibiotic for pertussis across all age groups due to superior tolerability, shorter treatment duration, and significantly lower risk of infantile hypertrophic pyloric stenosis (IHPS) compared to erythromycin. 1

Age-Specific Azithromycin Dosing

• Neonates (<1 month): 10 mg/kg/day for 5 days 2, 1

  • Azithromycin is strongly preferred in this age group; erythromycin carries a 5-10% absolute risk of IHPS and should be avoided 1
  • Monitor all neonates receiving any macrolide for IHPS symptoms: non-bilious vomiting and feeding-related irritability 1

• Infants 1-5 months: 10 mg/kg/day for 5 days 2, 1

  • Clarithromycin 15-20 mg/kg/day divided twice daily for 7 days is an acceptable alternative 2, 1

• Children ≥6 months and adolescents: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg/day (max 250 mg) on days 2-5 2, 1

• Adults: 500 mg on day 1, then 250 mg daily on days 2-5 2, 1, 3

Alternative Macrolide: Clarithromycin

• Children ≥6 months: 15-20 mg/kg/day divided twice daily for 7 days (max 1 g/day) 2, 1
• Adults: 500 mg twice daily for 7 days 2, 1
• Clarithromycin is not recommended in infants <1 month due to theoretical IHPS risk based on structural similarity to erythromycin 1

Erythromycin: Use Only When Necessary

• Children: 40-50 mg/kg/day in 4 divided doses for 14 days 2, 4
• Adults: 500 mg four times daily or 250 mg four times daily for 14 days 2, 4
• Avoid in infants <6 months due to unacceptably high IHPS risk (5.1% for 8-14 days, 10% for 15-21 days) 1
• Poor adherence due to gastrointestinal side effects and four-times-daily dosing 2

Alternative for Macrolide-Intolerant or Macrolide-Resistant Cases

Trimethoprim-sulfamethoxazole (TMP-SMZ) for 14 days is the recommended alternative for patients >2 months who cannot receive macrolides. 2, 1

TMP-SMZ Dosing

• Adults: One double-strength tablet (160 mg TMP/800 mg SMZ) twice daily for 14 days 2
• Children >2 months: 8 mg/kg/day TMP with 40 mg/kg/day SMZ in 2 divided doses for 14 days 2

Absolute Contraindications for TMP-SMZ

• Infants <2 months (risk of kernicterus) 1
• Pregnant women at term 2, 1
• Nursing mothers 2, 1

Macrolide-Resistant Pertussis

• In regions with documented macrolide resistance (e.g., China with 75% resistance rates), piperacillin-tazobactam or cefoperazone-sulbactam demonstrate excellent in vitro and clinical efficacy (96% microbiologic cure, 93.8% clinical improvement) 5
• These agents should be considered when macrolide resistance is confirmed or strongly suspected 5

Timing of Treatment and Clinical Effectiveness

Start antibiotics immediately upon clinical suspicion—do not wait for laboratory confirmation. 1, 3

• Catarrhal phase (first ~2 weeks): Antibiotics rapidly eradicate B. pertussis from the nasopharynx, reduce coughing paroxysms by approximately 50%, and decrease complications 2, 1
• Paroxysmal phase (>3 weeks from cough onset): Clinical benefit to the patient is minimal, but treatment remains essential to eliminate the organism and prevent transmission to vulnerable contacts 2, 1
• 80-90% of untreated patients spontaneously clear bacteria within 3-4 weeks, but untreated infants can remain culture-positive for >6 weeks 2, 1

Post-Exposure Prophylaxis (PEP)

Prophylaxis uses identical antimicrobial agents and dosing regimens as treatment. 2, 1, 6

Priority Groups for PEP (Administer Within 21 Days of Exposure)

• All household and close contacts, regardless of vaccination status 1, 6
• Infants <12 months, especially <4 months (highest risk of severe/fatal disease) 1, 6
• Pregnant women in third trimester 2, 1, 6
• Healthcare workers with documented exposure 2, 6
• Child-care workers who have contact with infants 6

Definition of Close Contact

Close contacts include persons with direct exposure to respiratory secretions during the catarrhal or paroxysmal stages (e.g., face-to-face contact within 3 feet, sharing confined spaces) 2, 6

PEP Effectiveness and Limitations

• PEP must be administered within 21 days of exposure to be effective 6
• Prophylaxis does not provide long-term protection; vaccination remains the most important preventive strategy 6
• Pertussis has a secondary attack rate exceeding 80% among susceptible household contacts 1, 6

Infection Control and Isolation

Isolate patients at home and away from work/school for 5 days after starting antibiotics. 1

• If antibiotics are not given, isolation must extend to 21 days from cough onset 1
• In healthcare facilities: place in private room or cohort with other pertussis patients; wear surgical mask when within 3 feet; maintain droplet precautions until 5 days of therapy completed 2, 1
• Symptomatic healthcare workers must be excluded from work for the first 5 days of antimicrobial therapy 2, 1

Critical Safety Considerations and Drug Interactions

Azithromycin

• Do not administer simultaneously with aluminum- or magnesium-containing antacids (reduces absorption) 1
• Use caution in patients with impaired hepatic function 1
• Does not inhibit cytochrome P450 enzymes (unlike erythromycin and clarithromycin) 1

Erythromycin and Clarithromycin

• Inhibit cytochrome P450 enzymes; avoid co-administration with astemizole, cisapride, pimozide, terfenadine, digoxin, triazolam, and ergot alkaloids 2, 1

Absolute Contraindications

• All macrolides are contraindicated in patients with known hypersensitivity to any macrolide agent 2, 1

Therapies Without Proven Benefit

Do not use long-acting β-agonists, antihistamines, systemic corticosteroids, or pertussis-specific immunoglobulin—these have no demonstrated benefit in controlling coughing paroxysms. 1

Hospitalization Criteria

• All infants <4 months should be strongly considered for hospital admission due to high risk of apnea, pneumonia, seizures, and death 1
• Infants <12 months with severe symptoms require admission 1
• Inpatient monitoring should include surveillance for bacterial pneumonia and otitis media 1

Common Clinical Pitfalls

• Do not withhold azithromycin in infants <6 months despite lack of FDA licensure—CDC explicitly recommends its use because benefits outweigh potential risks 1
• Do not use erythromycin in infants <6 months due to unacceptably high IHPS risk 1
• Do not delay treatment waiting for laboratory confirmation—clinical suspicion alone warrants immediate antibiotic initiation 1, 3
• Do not assume treatment is futile in the paroxysmal stage—while clinical benefit may be limited, treatment remains essential to prevent transmission 1