Effect of Early Administration of Clarithromycin or Azithromycin on Symptoms of Pertussis in Infants

Background: A resurgence of pertussis has been observed in several geographic areas in the post-COVID-19 era. Macrolides are the first-choice antibiotics for the treatment of pertussis. Limited data exist on the impact of the early administration of clarithromycin or azithromycin on infants' pertussis symptoms. Methods: This retrospective cohort study analyzed infants enrolled in an enhanced surveillance program for pertussis at a single Italian clinical reference center between 2015 and 2020. All cases were laboratory-confirmed. This study compared outcomes based on the timing of macrolide antibiotic treatment: early administration (within 7 days of cough onset) versus lateadministration (8 days or later). Key outcomes included cough duration, symptom frequency, and complication rates. Results: We studied 148 infants with confirmed pertussis. The median duration of coughing was 14 days in infants with early administration and 24 days in those with late administration. The occurrence of symptoms differed for apnea (62.6\% for early administration; 84.6\% for late administration). In a multivariable Cox model, the duration of the cough was lower in infants receiving antibiotics within 7 days from the beginning of the cough compared with those starting later (HR = 0.36, 95\% CI: 0.25-0.53, p < 0.001). Clarithromycin was associated with a shorter duration of coughing (HR = 0.42, 95\% CI: 0.19-0.92, p = 0.030) independently from other factors. Regarding the occurrence of symptoms, children receiving antibiotics later were three times more likely to experience apnea compared to those treated early (p = 0.008). Conclusions: Early treatment with clarithromycin or azithromycin for infants with pertussis improves clinical symptoms. Clarithromycin may be more effective than azithromycin in shortening coughing. The early administration of antibiotics may also help prevent the spread of disease during the resurgence of pertussis and should be considered regardless of the laboratory confirmation, while taking into account the potential side effects of an unnecessary therapy.