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Abstract

remains a major pathogen causing invasive diseases in children worldwide. Although pneumococcal conjugate vaccines (PCVs) have significantly reduced the disease burden, non-vaccine serotypes and antimicrobial resistance continue to be of concern.

The epidemiology of paediatric invasive pneumococcal disease (IPD) and antimicrobial resistance patterns in Japan following the coronavirus disease 2019 pandemic and prior to the introduction of PCV15 and PCV20 has not been fully characterized.

To investigate the recent distribution of pneumococcal serotypes, antimicrobial susceptibility and genetic characteristics of isolates derived from paediatric patients in Japan from 2020 to 2023.

We conducted a nationwide, prospective surveillance study from March 2020 to April 2023. A total of 151 pneumococcal isolates (126 from IPD cases and 25 from non-IPD cases) were collected from children under 15 years of age. Serotyping, antimicrobial susceptibility testing and whole-genome sequencing were performed to assess epidemiological and genomic features.

No patient mortality was reported, but sequelae were observed in 4 (3.2%) of 125 IPD patients. The most common serotypes in IPD were 15B/C (23.0%), 15A (11.1%) and 24B (10.3%). Among 126 IPD isolates, the vaccine coverage rates for PCV13, 15 and 20 were 0.8, 13.5 and 42.1%, respectively. Overall resistance rates to penicillin (PEN), cefotaxime, meropenem (MEM) and erythromycin (ERY) were 31.8, 15.9, 18.5 and 88.7%, respectively. Serotypes 15A-CC63 and 35B-CC558 showed high resistance rates to -lactams, including MEM. Genomic analysis revealed that the predominant genotypes were 15B/C-CC199, 15A-CC63, 24B-CC2754 and 10A-CC5236.

Non-vaccine and PEN-, MEM- and ERY-resistant clones, particularly 15A-CC63 and 35B-CC558, were prevalent among paediatric pneumococci in Japan. Even with PCV20, less than half of the IPD isolates were covered; this underscores the need for ongoing genomic surveillance, antimicrobial stewardship and consideration of expanded-valency vaccines targeting additional serotypes, such as 15A and 35B.

Funding
This study was supported by the:
  • the Japan Society for the Promotion of Science (Award 23K07957)
    • Principal Award Recipient: SatoshiNakano
  • the Japan Society for the Promotion of Science (Award 21K15432)
    • Principal Award Recipient: SatoshiNakano
  • Pfizer (Award research grant)
    • Principal Award Recipient: TakaoFujisawa
  • Japan Agency for Medical Research and Development (Award JP20fk0108147)
    • Principal Award Recipient: SatoshiNakano
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/jmm/10.1099/jmm.0.002105
2025-12-12
2026-01-19

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References

  1. Li L, Ma J, Yu Z, Li M, Zhang W et al. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: an updated review. Microbiol Res 2023; 266:127221 [View Article] [PubMed]
    [Google Scholar]
  2. Wahl B, O’Brien KL, Greenbaum A, Majumder A, Liu L et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018; 6:e744–e757 [View Article] [PubMed]
    [Google Scholar]
  3. Danino D, Ben-Shimol S, van der Beek BA, Givon-Lavi N, Avni YS et al. Decline in pneumococcal disease in young children during the coronavirus disease 2019 (COVID-19) pandemic in israel associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study. Clin Infect Dis 2022; 75:e1154–e1164 [View Article] [PubMed]
    [Google Scholar]
  4. Kajihara T, Yahara K, Kamigaki T, Hirabayashi A, Hosaka Y et al. Effects of coronavirus disease 2019 on the spread of respiratory-transmitted human-to-human bacteria. J Infect 2024; 89:106201 [View Article] [PubMed]
    [Google Scholar]
  5. Huang L, Li X, Eugenia N, Leung J, Hung S-TA et al. Burden of pneumococcal disease in young children due to serotypes contained in different pneumococcal conjugate vaccines in eight Asian countries and territories. Vaccines 2024; 12:1197 [View Article] [PubMed]
    [Google Scholar]
  6. Zhang D, Petigara T, Yang X. Clinical and economic burden of pneumococcal disease in US adults aged 19-64 years with chronic or immunocompromising diseases: an observational database study. BMC Infect Dis 2018; 18:436 [View Article] [PubMed]
    [Google Scholar]
  7. Centers for Disease Control and Prevention (CDC) Active bacterial core surveillance report, Emerging Infections Program Network, Group A Streptococcus, 2019; 2019 https://www.cdc.gov/abcs/downloads/gas_surveillance_report_2019.pdf
  8. Suga S, Chang B, Asada K, Akeda H, Nishi J et al. Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: effects of the seven-valent pneumococcal conjugate vaccine. Vaccine 2015; 33:6054–6060 [View Article] [PubMed]
    [Google Scholar]
  9. Nakano S, Fujisawa T, Ito Y, Chang B, Suga S et al. Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012-2014. Vaccine 2016; 34:67–76 [View Article] [PubMed]
    [Google Scholar]
  10. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y et al. Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015-2017. Vaccine 2020; 38:1818–1824 [View Article] [PubMed]
    [Google Scholar]
  11. Kaplan SL, Barson WJ, Lin PL, Stovall SH, Bradley JS et al. Serotype 19A Is the most common serotype causing invasive pneumococcal infections in children. Pediatrics 2010; 125:429–436 [View Article] [PubMed]
    [Google Scholar]
  12. Maraki S, Samonis G, Galanakis E. Serotypes and susceptibilities of paediatric clinical isolates of Streptococcus pneumoniae in Crete, Greece, before and after the heptavalent pneumococcal conjugate vaccine. Eur J Clin Microbiol Infect Dis 2010; 29:1449–1451 [View Article] [PubMed]
    [Google Scholar]
  13. Navarro Torné A, Dias JG, Quinten C, Hruba F, Busana MC et al. European enhanced surveillance of invasive pneumococcal disease in 2010: data from 26 European countries in the post-heptavalent conjugate vaccine era. Vaccine 2014; 32:3644–3650 [View Article] [PubMed]
    [Google Scholar]
  14. Shin J, Baek JY, Kim SH, Song JH, Ko KS. Predominance of ST320 among Streptococcus pneumoniae serotype 19A isolates from 10 Asian countries. J Antimicrob Chemother 2011; 66:1001–1004 [View Article] [PubMed]
    [Google Scholar]
  15. Elmdaghri N, Benbachir M, Belabbes H, Zaki B, Benzaid H. Changing epidemiology of pediatric Streptococcus pneumoniae isolates before vaccine introduction in Casablanca (Morocco). Vaccine 2012; 30 Suppl 6:G46–50 [View Article] [PubMed]
    [Google Scholar]
  16. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y et al. Whole-genome sequencing analysis of multidrug-resistant serotype 15A Streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone. Antimicrob Agents Chemother 2019; 63:e02579-18 [View Article] [PubMed]
    [Google Scholar]
  17. Shinohara K, Fujisawa T, Chang B, Ito Y, Suga S et al. Frequent transmission of Streptococcus pneumoniae serotype 35B and 35D, clonal complex 558 lineage, across continents and the formation of multiple clades in Japan. Antimicrob Agents Chemother 2023; 67:e0108322 [View Article] [PubMed]
    [Google Scholar]
  18. Nakano S, Fujisawa T, Chang B, Ito Y, Akeda H et al. Whole-genome analysis-based phylogeographic investigation of Streptococcus pneumoniae serotype 19A sequence type 320 isolates in Japan. Antimicrob Agents Chemother 2022; 66:e0139521 [View Article] [PubMed]
    [Google Scholar]
  19. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y et al. Spread of meropenem-resistant Streptococcus pneumoniae serotype 15A-ST63 clone in Japan, 2012-2014. Emerg Infect Dis 2018; 24:275–283 [View Article] [PubMed]
    [Google Scholar]
  20. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y et al. Penicillin-binding protein typing, antibiotic resistance gene identification, and molecular phylogenetic analysis of meropenem-resistant Streptococcus pneumoniae serotype 19A-CC3111 strains in Japan. Antimicrob Agents Chemother 2019; 63:e00711-19 [View Article] [PubMed]
    [Google Scholar]
  21. Kajihara T, Yahara K, Hirabayashi A, Shibayama K, Sugai M. Japan Nosocomial Infections Surveillance (JANIS): current Status, international collaboration, and future directions for a comprehensive antimicrobial resistance surveillance system. Jpn J Infect Dis 2021; 74:87–96 [View Article] [PubMed]
    [Google Scholar]
  22. Almeida SCG, Lemos APS de, Bierrenbach AL, Moraes JC de, Brandileone MC de C. Serotype distribution and antimicrobial susceptibility pattern of Streptococcus pneumoniae in COVID-19 pandemic era in Brazil. Microorganisms 2024; 12:401 [View Article] [PubMed]
    [Google Scholar]
  23. Hirabayashi A, Kajihara T, Yahara K, Shibayama K, Sugai M. Impact of the COVID-19 pandemic on the surveillance of antimicrobial resistance. J Hosp Infect 2021; 117:147–156 [View Article] [PubMed]
    [Google Scholar]
  24. Hyams C, Challen R, Hettle D, Amin-Chowdhury Z, Grimes C et al. Serotype distribution and disease severity in adults hospitalized with Streptococcus pneumoniae infection, Bristol and Bath, UK, 2006‒2022. Emerg Infect Dis 2023; 29:1953–1964 [View Article]
    [Google Scholar]
  25. Shaw D, Abad R, Amin-Chowdhury Z, Bautista A, Bennett D et al. Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium. Lancet Digit Health 2023; 5:e582–e593 [View Article] [PubMed]
    [Google Scholar]
  26. Tigoi CC, Gatakaa H, Karani A, Mugo D, Kungu S et al. Rates of acquisition of pneumococcal colonization and transmission probabilities, by serotype, among newborn infants in Kilifi District, Kenya. Clin Infect Dis 2012; 55:180–188 [View Article] [PubMed]
    [Google Scholar]
  27. Ai L, Zhou C, Fang L, Liu B, Gong F. Changes in the epidemiology and antimicrobial resistance patterns of Streptococcus pneumoniae from pediatric community acquired pneumonia patients attended in a Chinese hospital during the COVID-19 pandemic. Infection 2024; 52:2455–2464 [View Article] [PubMed]
    [Google Scholar]
  28. Bondi A, Koumantakis E, Curtoni A, Barbui AM, Peradotto M et al. Epidemiology and impact of anti-pneumococcal vaccination and COVID-19 on resistance of Streptococcus pneumoniae causing invasive disease in Piedmont, Italy. Antibiotics (Basel) 2024; 13:740 [View Article] [PubMed]
    [Google Scholar]
  29. CLSI Performance standards for antimicrobial susceptibility testing; twenty-fifth informational supplement. CLSI document M100-S25. Clinical and Laboratory Standards Institute; 2015
  30. Enright MC, Spratt BG. A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease. Microbiology 1998; 144:3049–3060 [View Article] [PubMed]
    [Google Scholar]
  31. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE Jr et al. Penicillin-binding protein transpeptidase signatures for tracking and predicting β-lactam resistance levels in Streptococcus pneumoniae. mBio 2016; 7:e00756-16 [View Article] [PubMed]
    [Google Scholar]
  32. Metcalf BJ, Gertz RE Jr, Gladstone RA, Walker H, Sherwood LK et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect 2016; 22:60 [View Article] [PubMed]
    [Google Scholar]
  33. Metcalf BJ, Chochua S, Gertz RE Jr, Li Z, Walker H et al. Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States. Clin Microbiol Infect 2016; 22:1002 [View Article] [PubMed]
    [Google Scholar]
  34. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y et al. Streptococcus pneumoniae serotype 12F-CC4846 and invasive pneumococcal disease after introduction of 13-valent pneumococcal conjugate vaccine, Japan, 2015–2017. Emerg Infect Dis 2020; 26:2660–2668 [View Article]
    [Google Scholar]
  35. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article] [PubMed]
    [Google Scholar]
  36. Pathogenwatch. A Global Platform for Genomic Surveillance. Centre for Genomic Pathogen Surveillance; n.d https://pathogen.watch/ accessed 25 November 2024
  37. Page AJ. Pathogen genomics TWTSI, Wellcome Trust Genome Campus, Hinxton, Cambridge, Cummins CA, pathogen genomics TWTSI, Wellcome Trust Genome Campus, Hinxton, Cambridge, Hunt M et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2019; 31:3691–3693
    [Google Scholar]
  38. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [View Article] [PubMed]
    [Google Scholar]
  39. Brueggemann AB, Jansen van Rensburg MJ, Shaw D, McCarthy ND, Jolley KA et al. Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the invasive respiratory infection surveillance initiative: a prospective analysis of surveillance data. Lancet Digit Health 2021; 3:e360–e370 [View Article] [PubMed]
    [Google Scholar]
  40. Lo SW, Mellor K, Cohen R, Alonso AR, Belman S et al. Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study. Lancet Microbe 2022; 3:e735–e743 [View Article] [PubMed]
    [Google Scholar]
  41. Muraki Y, Yagi T, Tsuji Y, Nishimura N, Tanabe M et al. Japanese antimicrobial consumption surveillance: first report on oral and parenteral antimicrobial consumption in Japan (2009-2013). J Glob Antimicrob Resist 2016; 7:19–23 [View Article] [PubMed]
    [Google Scholar]
  42. Okubo Y, Uda K, Miyairi I. Long-term effectiveness of financial incentives for not prescribing unnecessary antibiotics to children with acute respiratory and gastrointestinal infections: Japan’s Nationwide Quasi-Experimental Study. Clin Infect Dis 2025; 81:602–609 [View Article] [PubMed]
    [Google Scholar]
  43. Högberg L, Geli P, Ringberg H, Melander E, Lipsitch M et al. Age- and serogroup-related differences in observed durations of nasopharyngeal carriage of penicillin-resistant pneumococci. J Clin Microbiol 2007; 45:948–952 [View Article] [PubMed]
    [Google Scholar]
  44. Pallares R, Gudiol F, Liñares J, Ariza J, Rufi G et al. Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin-resistant pneumococci. N Engl J Med 1987; 317:18–22 [View Article] [PubMed]
    [Google Scholar]
  45. Ruhe JJ, Hasbun R. Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance. Clin Infect Dis 2003; 36:1132–1138 [View Article] [PubMed]
    [Google Scholar]
  46. Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. Lancet Infect Dis 2019; 19:759–769 [View Article] [PubMed]
    [Google Scholar]
  47. Cleary DW, Jones J, Gladstone RA, Osman KL, Devine VT et al. Changes in serotype prevalence of Streptococcus pneumoniae in Southampton, UK between 2006 and 2018. Sci Rep 2022; 12:13332 [View Article] [PubMed]
    [Google Scholar]
  48. Kavalari ID, Fuursted K, Krogfelt KA, Slotved HC. Molecular characterization and epidemiology of Streptococcus pneumoniae serotype 24F in Denmark. Sci Rep 2019; 9:5481 [View Article] [PubMed]
    [Google Scholar]
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