eprintid: 10191540 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/19/15/40 datestamp: 2024-05-02 13:31:54 lastmod: 2024-05-02 13:31:54 status_changed: 2024-05-02 13:31:54 type: article metadata_visibility: show sword_depositor: 699 creators_name: Rodriguez-Ruiz, Juan Pablo creators_name: Xavier, Basil Britto creators_name: Stöhr, Wolfgang creators_name: van Heirstraeten, Liesbet creators_name: Lammens, Christine creators_name: Finn, Adam creators_name: Goossens, Herman creators_name: Bielicki, Julia Anna creators_name: Sharland, Michael creators_name: Malhotra-Kumar, Surbhi creators_name: PERUKI, GAPRUKI and CAP-IT networks, title: High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: Beta-lactams, Streptococcus pneumoniae, Emerging serotype, Vaccine escape, Population genomics, Vaccine types, Non-vaccine types note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. abstract: BACKGROUND: Streptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/ ) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles. METHODS: Three-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences. RESULTS: Among 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event. CONCLUSIONS: Our data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance. date: 2024-04-27 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1186/s12866-024-03300-w oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2271719 doi: 10.1186/s12866-024-03300-w medium: Electronic pii: 10.1186/s12866-024-03300-w lyricists_name: Stohr, Wolfgang lyricists_id: WSTOH63 actors_name: Stohr, Wolfgang actors_id: WSTOH63 actors_role: owner funding_acknowledgements: 13/88/11 [National Institute for Health Research (NIHR) Health Technology Assessment Programme, Antimicrobial Resistance Themed Call]; 13/88/11 [National Institute for Health Research (NIHR) Health Technology Assessment Programme, Antimicrobial Resistance Themed Call]; 13/88/11 [National Institute for Health Research (NIHR) Health Technology Assessment Programme, Antimicrobial Resistance Themed Call]; 13/88/11 [National Institute for Health Research (NIHR) Health Technology Assessment Programme, Antimicrobial Resistance Themed Call] full_text_status: public publication: BMC Microbiology volume: 24 article_number: 146 event_location: England issn: 1471-2180 citation: Rodriguez-Ruiz, Juan Pablo; Xavier, Basil Britto; Stöhr, Wolfgang; van Heirstraeten, Liesbet; Lammens, Christine; Finn, Adam; Goossens, Herman; ... PERUKI, GAPRUKI and CAP-IT networks; + view all <#> Rodriguez-Ruiz, Juan Pablo; Xavier, Basil Britto; Stöhr, Wolfgang; van Heirstraeten, Liesbet; Lammens, Christine; Finn, Adam; Goossens, Herman; Bielicki, Julia Anna; Sharland, Michael; Malhotra-Kumar, Surbhi; PERUKI, GAPRUKI and CAP-IT networks; - view fewer <#> (2024) High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland. BMC Microbiology , 24 , Article 146. 10.1186/s12866-024-03300-w <https://doi.org/10.1186/s12866-024-03300-w>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10191540/1/s12866-024-03300-w.pdf