What is the appropriate erythromycin prophylaxis regimen (dose and duration) for close contacts of a pertussis case, including alternatives for intolerance?

Erythromycin Prophylaxis for Pertussis Contacts

Erythromycin is no longer the preferred agent for pertussis prophylaxis—azithromycin should be used instead due to superior tolerability, shorter treatment duration, and significantly better compliance rates. 1

Recommended Prophylaxis Regimen

First-Line: Azithromycin (Preferred)

Adults:

• 500 mg on day 1, then 250 mg daily on days 2-5 (total 5 days) 1

Children ≥6 months:

• 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg/day (max 250 mg) on days 2-5 1

Infants <6 months:

• 10 mg/kg/day for 5 days 1

Infants <1 month:

• Azithromycin 10 mg/kg/day for 5 days is strongly preferred over erythromycin due to 5-10% absolute risk of infantile hypertrophic pyloric stenosis (IHPS) with erythromycin 1

If Erythromycin Must Be Used

Only consider erythromycin if azithromycin is unavailable or contraindicated:

Adults:

• Erythromycin estolate 500 mg four times daily OR erythromycin delayed-release 333 mg three times daily for 14 days 1

Children (except infants <2 weeks):

• 40-50 mg/kg/day divided into doses for 14 days 1

Critical caveat: Erythromycin should be avoided in infants <6 months due to unacceptably high IHPS risk 1

Alternative for Macrolide Intolerance

Trimethoprim-sulfamethoxazole (TMP-SMZ) for 14 days (only for patients >2 months):

Adults:

• One double-strength tablet (160/800 mg) twice daily 1

Children >2 months:

• TMP 8 mg/kg/day, SMZ 40 mg/kg/day in 2 divided doses 1

Absolute contraindications for TMP-SMZ: Pregnant women at term, nursing mothers, infants <2 months 1

Who Should Receive Prophylaxis

Administer prophylaxis within 21 days of exposure to: 2

• All household contacts regardless of vaccination status 1, 3
• Infants <12 months (especially <4 months—highest risk of severe/fatal disease) 2
• Pregnant women in third trimester 2
• Healthcare workers with documented exposure 2
• Child-care workers who have contact with infants 2

Why Azithromycin Over Erythromycin

Compliance data strongly favor azithromycin:

• 93% completion rate with azithromycin vs. 57% with erythromycin 4
• 76% of erythromycin non-completers stopped due to gastrointestinal side effects 4
• Azithromycin has 4.5 times higher completion rate (95% CI 2.9-7.0) 4

Equivalent microbiologic efficacy:

• Both eradicate Bordetella pertussis equally (RR 1.02,95% CI 0.98-1.05) 5
• Shorter macrolides have 34% fewer side effects than 14-day erythromycin (RR 0.66,95% CI 0.52-0.83) 5

Critical Timing Considerations

Prophylaxis must be initiated within 21 days of exposure to be effective 2

Patients are most infectious during:

• Catarrhal stage (first 1-2 weeks) 2
• First 3 weeks after cough onset 2
• Secondary attack rate exceeds 80% among susceptible household contacts 2, 3

Vaccination Status of Contacts

All close contacts <7 years who have not completed the 4-dose primary series should complete it with minimal intervals 1, 3

Those who completed primary series but have not received pertussis vaccine within 3 years of exposure should receive a booster dose 1, 3

Special Populations

Pregnant women:

• Use azithromycin at adult dosing (500 mg day 1, then 250 mg daily days 2-5) 2
• Never use TMP-SMZ at term 1

Breastfeeding mothers:

• Azithromycin is safe 2
• TMP-SMZ is contraindicated 1

Healthcare workers:

• Asymptomatic workers receiving prophylaxis can continue patient care 1, 3
• Symptomatic workers must be excluded for first 5 days of antibiotic therapy 1

Common Pitfalls to Avoid

Do not use erythromycin in infants <6 months—the IHPS risk (5-10% absolute risk) outweighs any benefit when azithromycin is available 1

Do not delay prophylaxis while awaiting laboratory confirmation—clinical suspicion alone warrants immediate treatment 6

Do not assume vaccination provides complete protection—immunity wanes 5-10 years after vaccination, making adolescents and adults susceptible 3

Do not use passive immunization (pertussis immune globulin)—it is ineffective and no longer available 1, 3

Azithromycin should not be taken with aluminum- or magnesium-containing antacids as they reduce absorption 1

Erythromycin and clarithromycin inhibit cytochrome P450 enzymes—avoid co-administration with astemizole, cisapride, pimozide, or terfenadine 1

Infection Control During Prophylaxis

Isolate confirmed cases at home for 5 days after starting antibiotics (or 21 days from cough onset if untreated) 2, 6

In healthcare settings:

• Wear surgical mask within 3 feet of suspected/confirmed cases 1
• Place patients in private rooms or cohort with other pertussis patients 1
• Maintain droplet precautions until 5 days of therapy completed 1