Changes in composition of respiratory bacteria colonizing pneumococcal conjugate vaccinated children, 2006–2023

We hypothesized that the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) would alter patterns of nasopharyngeal colonization and their relationship to acute otitis media (AOM) in children. We prospectively followed 1537 children from age 6-36 months across three periods: 2006-2009 (PCV7 era), 2010-2014 (early-PCV13 era), and 2015-2023 (late-PCV13 era), collecting nasopharyngeal cultures at healthy and AOM visits, with paired tympanocentesis when appropriate. Colonized children had more frequent daycare attendance and less breastfeeding. Children with no AOM differed from those with uncomplicated AOM (uAOM) by less colonization with respiratory pathogens. Complex AOM (cAOM) nasopharyngeal samples exhibited a higher frequency of Haemophilus influenzae, and vaccine serotype Streptococcus pneumoniae, compared to no AOM and uAOM children. Serotype distribution of S. pneumoniae changed, with replacement of PCV13 serotypes. Streptococcus pneumoniae nasopharyngeal isolation rates remained stable despite serotype replacement. Haemophilus influenzae isolation rates remained constant and Moraxella catarrhalis increased. Nasopharyngeal culture was a poor predictor of middle ear fluid culture. Respiratory bacterial pathogen distribution in healthy children and those with uAOM were similar and both were distinct from cAOM, with significant vaccine-driven serotype replacement occurring without reducing overall pneumococcal colonization.