A randomized, placebo-controlled trial of erythromycin estolate chemoprophylaxis for household contacts of children with culture-positive Bordetella pertussis infection

Context. Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis. Objective. To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis. Design. Randomized, double-blind, placebo-controlled study. Setting. Community based. Subjects. All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. Interventions. Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment. Primary Outcome. Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis. Results. There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin- treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients. Conclusions. Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.