Is chemoprophylaxis (use of medications to prevent disease, such as azithromycin) necessary for individuals in close contact with a pertussis (whooping cough) patient, particularly those at high risk of severe disease, including young children, pregnant women, and individuals with underlying medical conditions like immunodeficiency or chronic respiratory disease?

Chemoprophylaxis for Pertussis Contacts

Yes, chemoprophylaxis with a macrolide antibiotic is strongly recommended for all close contacts of pertussis patients, regardless of age or vaccination status, to prevent transmission and protect high-risk individuals from severe disease and death. 1

Who Should Receive Chemoprophylaxis

All close contacts should receive prophylaxis, defined as anyone who has had direct contact of their nasal or buccal mucosa with respiratory secretions of an untreated person in the catarrhal or paroxysmal stage of pertussis. 1 This includes:

• All household members regardless of vaccination status 1, 2
• Healthcare workers with close exposure 1
• Individuals at highest risk including neonates, infants ≤12 months, pregnant women in third trimester, elderly individuals, and those with cardiac/respiratory insufficiency 3, 4

The rationale is clear: pertussis has a secondary attack rate exceeding 80% among susceptible household contacts, and one active case can infect 70-100% of susceptible household members. 2

Timing Is Critical

Chemoprophylaxis must be initiated within 21 days of symptom onset in the index case to be effective. 1, 4, 5

• Optimal window: <14 days after primary patient's symptom onset, when effectiveness is 43.9% 5
• Acceptable window: <21 days for high-risk household contacts 3, 4
• No benefit beyond 21 days from symptom onset 1, 4

The effectiveness decreases significantly when started >14 days after the primary patient's symptom onset. 5

First-Line Regimen: Macrolides

Azithromycin is the preferred agent due to shorter duration and better tolerability compared to erythromycin. 1, 2

Adults and Adolescents:

• Azithromycin: 500 mg on day 1, then 250 mg daily for 4 days (5-day course) 1, 2, 6
• Clarithromycin: 500 mg twice daily for 10-14 days 1, 2
• Erythromycin: 500 mg four times daily OR 333 mg three times daily (delayed-release) for 14 days 1

Children:

• Azithromycin: 10 mg/kg on day 1, then 5 mg/kg daily for 4 days 1, 2
• Clarithromycin: 15-20 mg/kg/day in two divided doses for 10-14 days 1
• Erythromycin: 40-50 mg/kg/day for 14 days (except infants <2 weeks) 1

Infants <2 Weeks:

• Use azithromycin or clarithromycin instead of erythromycin due to risk of infantile hypertrophic pyloric stenosis 1

Alternative for Macrolide Intolerance

For patients with macrolide hypersensitivity or intolerance, use trimethoprim-sulfamethoxazole for 14 days. 1

• Adults: One double-strength tablet (160/800 mg) twice daily 1, 6
• Children: 8 mg/kg/day TMP, 40 mg/kg/day SMX in 2 divided doses 1

Important contraindications: Do not use in pregnant women at term, nursing mothers, or infants <2 months. 1

Vaccination Status of Contacts

Chemoprophylaxis does not replace vaccination—both are needed. 2

• Children <7 years who haven't completed the 4-dose primary series should complete it with minimal intervals 1, 2
• Those with completed primary series but no pertussis vaccine within 3 years of exposure should receive a booster dose 1, 2

Healthcare Worker Considerations

Asymptomatic healthcare workers receiving chemoprophylaxis can continue patient care without work exclusion. 1

However, if unable to receive chemoprophylaxis, exclude them from caring for children <4 years for 7 days after first exposure until 14 days after last exposure. 1

Evidence Quality and Clinical Pearls

The evidence supporting chemoprophylaxis comes primarily from CDC guidelines with IB-level recommendations (strongly recommended based on well-designed studies). 1 A randomized controlled trial demonstrated 67.5% efficacy in preventing culture-positive pertussis in household contacts, though it did not prevent all clinical pertussis. 7

Common pitfalls to avoid:

• Don't delay treatment waiting for culture confirmation—start immediately upon clinical suspicion 6
• Don't forget that vaccinated individuals can still transmit pertussis, as immunity wanes 5-10 years after vaccination 2, 6
• Don't use passive immunization—human pertussis immune globulin is not effective and no longer available 1, 2
• Be aware of erythromycin side effects (34% adverse reaction rate vs 15.7% for placebo), which may limit compliance 7

The bottom line: Chemoprophylaxis is a critical public health measure that reduces transmission to vulnerable populations, particularly young infants at risk of severe disease and death. When initiated promptly within 14-21 days of exposure, it provides meaningful protection despite not being 100% effective. 3, 4, 5