Collection of 390 S. pneumoniae isolates obtained from nasopharynx of children presenting with community-acquired pneumonia in the UK and Ireland.
We studied genomic epidemiology and mechanisms underlying persistence of pneumococcal (vaccine) serotypes in the framework of a 2X2 factorial trial (CAP-IT) that collected nasopharyngeal swabs from >6-months old children attending hospital with clinically-diagnosed CAP, and randomized to receive lower versus higher dose, and longer versus shorter duration of amoxicillin. 390 pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin.  Serotypes 15B/C, 11A, 15A and 23B1 were most prevalent. PCV13 serotypes 3, 19A, and 19F were also identified (n=25, 6·4%). Capsular-switch events were frequent among 19A and 19F, whereas serotype 3 genomes (n=13, 3·3%) were highly stable over a 20-year period. All 23B1 isolates (n=27, 6·9%) were penicillin non-susceptible, and one had resulted from a potential capsule-switch in 19F.  Our data suggest that vaccination strategies, but not amoxicillin use, might drive pneumococcal serotype prevalence among children in the UK and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease invasive disease in this target population. Emergence of 23B1, a non-vaccine sub-serotype with penicillin non-susceptibility, might provide a persistence strategy for vaccine serotypes, highlighting the need for continued genomic surveillance.