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SDG 3: Antimicrobial resistance

Abstract

BACKGROUND

Fifteen- and 20-valent pneumococcal conjugate vaccines (PCVs) offer broader protection against invasive pneumococcal disease (IPD) than PCV13. Adopting these vaccines may result in decreasing IPD incidence, antibiotic use and antimicrobial resistance (AMR) rates. If the additional serotypes in PCV15 and PCV20 are associated with AMR, AMR rate reduction could be greater than expected from reduced antibiotic consumption alone.

AIM

This retrospective analysis assessed the association between AMR and non-PCV13 serotypes in PCV15 and PCV20.

METHODS

Laboratory-based surveillance data on 8,123 IPD isolates were obtained retrospectively from the Belgian Reference Centre for invasive . Isolates (n = 8,088) were serotyped and tested for AMR. Associations between vaccine serotype groups and AMR were evaluated by multinomial logistic regression. Where associations varied with patients’ age, ranges of odds ratios (ORs) are presented.

RESULTS

PCV15-non-PCV13 and PCV20-non-PCV13 serotypes accounted for 7.4% (n = 597) and 37% (n = 2,992) of IPD isolates respectively. Of non-PCV20 serotypes, 24% (508/2,125) were penicillin resistant. Compared with non-PCV20 serotypes, PCV15-non-PCV13 serotypes were more often associated with erythromycin (ORs: 3.59–9.43) and tetracycline (OR: 2.00) resistance, and with trimethoprim/sulfamethoxazole (OR: 0.11) susceptibility. PCV20-non-PCV15 serotypes were more often associated with amoxicillin (OR: 9.45) and cefotaxime (ORs: 5.06–82.38) resistance, and with erythromycin (ORs: 0.13–0.18), tetracycline (OR: 0.71) and penicillin (ORs: 0.05–0.46) susceptibility.

CONCLUSION

PCV20 may lead to a larger decrease in overall IPD incidence than PCV15. Although the PCV20 vaccination impact on AMR may be limited, some resistant or difficult to treat infections could be avoided. Serotype replacement might lead to infections with low level penicillin resistance increasing, but most of these should remain treatable.

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2025-12-05
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References

  1. Li L, Ma J, Yu Z, Li M, Zhang W, Sun H. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: An updated review. Microbiol Res. 2023;266:127221. https://doi.org/10.1016/j.micres.2022.127221 PMID:36244081  PMID: 36244081 
  2. Scelfo C, Menzella F, Fontana M, Ghidoni G, Galeone C, Facciolongo NC. Pneumonia and Invasive Pneumococcal Diseases: The Role of Pneumococcal Conjugate Vaccine in the Era of Multi-Drug Resistance. Vaccines (Basel). 2021;9(5):420.  https://doi.org/10.3390/vaccines9050420  PMID: 33922273 
  3. Robert E, Coppieters Y, Swennen B. Enquête de couverture vaccinale des enfants de 18 à 24 mois en Région de Bruxelles-Capitale. [Survey of vaccination coverage among children aged 18 to 24 months in the Brussels-Capital Region]. Bruxelles; 2020. French. Available from: https://dipot.ulb.ac.be/dspace/bitstream/2013/315101/3/Rapportbruxelles2020.pdf
  4. Robert E, Coppieters Y, Swennen B. Enquête de couverture vaccinale des enfants de 18 à 24 mois en Fédération Wallonie-Bruxelles, Bruxelles excepté. [Survey of vaccination coverage among children aged 18 to 24 months in the Wallonia-Brussels Federation, excluding Brussels]. Bruxelles; 2020. French. Available from: https://dipot.ulb.ac.be/dspace/bitstream/2013/315100/3/RapportWallonieoct2020.pdf
  5. Vandermeulen C, Hoppenbrouwers K, Roelants M, Theeten H, Braeckman T, Maertens K, et al. Studie van de vaccinatiegraad in Vlaanderen 2016. [Study of the vaccination rate in Flanders 2016]. 2017. Flemish. Available from: https://www.laatjevaccineren.be/sites/default/files/2022-04/Vaccinatiegraadstudie 2016.pdf
  6. Sciensano. Communicable Diseases: Vaccine-preventable diseases, Health Status Report. Brussels, Belgium. 2025. Available from: https://www.healthybelgium.be/en/health-status/communicable-diseases/vaccine preventable diseases
  7. Hoge Gezondheidsraad. Vaccinatie van kinderen en adolescenten tegen pneumokokken (HGR 8813). [Vaccination of children and adolescents against pneumococci (Superior Health Council 8813)]. Flemish. 2015. Available from: https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/19103440/Vaccinatie van kinderen en adolescenten tegen pneumokokken %28mei 2015%29%28HGR 8813%29.pdf
  8. Sleurs E, Vandeurzen J. Schriftelijke vraag en antwoord nr. 293 - Pneumokokkenvaccin - Stand van zaken. Vlaams Parlement [Written Question and Answer No. 293 - Pneumococcal Vaccine - Current Status. Flemish Parliament ]; 2019. p. 4. Flemish. Available from: https://docs.vlaamsparlement.be
  9. Ekinci E, Van Heirstraeten L, Willen L, Desmet S, Wouters I, Vermeulen H, et al. , NP Carriage Study Group. Serotype 19A and 6C Account for One-Third of Pneumococcal Carriage Among Belgian Day-Care Children Four Years After a Shift to a Lower-Valent PCV. J Pediatric Infect Dis Soc. 2023;12(1):36-42.  https://doi.org/10.1093/jpids/piac117  PMID: 36377804 
  10. Hoge Gezondheidsraad. HGR 9674: Vaccinatie tegen pneumokokken (Volwassenen). [Superior Health Council 9674: Vaccination against pneumococci (adults)]. Brussel; 2022. Flemish. Available from: https://www.hgr-css.be/file/download/eb6ecb38-930b-49ef-8717-5e60738337fc/hLQJH3kML5i9B6SPX11FQp6uFoPRG3jNn1neEHLleT43d.pdf
  11. Desmet S, Lagrou K, Wyndham-Thomas C, Braeye T, Verhaegen J, Maes P, et al. Dynamic changes in paediatric invasive pneumococcal disease after sequential switches of conjugate vaccine in Belgium: a national retrospective observational study. Lancet Infect Dis. 2021;21(1):127-36.  https://doi.org/10.1016/S1473-3099(20)30173-0  PMID: 32702303 
  12. European Medicines Agency (EMA). Prevenar 20 (previously Apexxnar): pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed). Amsterdam: EMA; 2025. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-20
  13. Europen Medicines Agency (EMA). Vaxneuvance: pneumococcal polysaccharide conjugate vaccine (adsorbed). Amsterdam: EMA; 2025. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/vaxneuvance
  14. Pfizer. European Commission Approves Pfizer’s PREVENAR 20 to Help Protect Infants and Children Against Pneumococcal Disease. 2024. Available from: https://www.pfizer.com/news/press-release/press-release-detail/european-commission-approves-pfizers-prevenar-20r-help
  15. Hoge Gezondheidsraad. Vaccinatie van kinderen en adolescenten tegen pneumokokken (HGR 9746). [Vaccination of children and adolescents against pneumococci (Superior Health Council 9746)]. 2023. Available from: https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/20230116_hgr_9746_fiche_vaccinatie_pneumokokken_kinderen_adolescenten.pdf
  16. Grant LR, Hanquet G, Sepúlveda-Pachón IT, Theilacker C, Baay M, Slack MPE, et al. Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance. Vaccine. 2024;42(12):2983-93.  https://doi.org/10.1016/j.vaccine.2024.03.065  PMID: 38553292 
  17. Jansen KU, Knirsch C, Anderson AS. The role of vaccines in preventing bacterial antimicrobial resistance. Nat Med. 2018;24(1):10-9.  https://doi.org/10.1038/nm.4465  PMID: 29315295 
  18. Ministry of Health. BELMAP 2024: One Health Report on Antimicrobial Use and Antimicrobial Resistance in Belgium. Brussels; 2024. Available from: https://www.moh.gov.sg/docs/librariesprovider5/resources-statistics/reports/one-health-report-on-antimicrobial-utilisation-and-resistance-2017.pdf
  19. Tomczyk S, Lynfield R, Schaffner W, Reingold A, Miller L, Petit S, et al. Prevention of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease With the 13-Valent Pneumococcal Conjugate Vaccine. Clin Infect Dis. 2016;62(9):1119-25.  https://doi.org/10.1093/cid/ciw067  PMID: 26908787 
  20. Hampton LM, Farley MM, Schaffner W, Thomas A, Reingold A, Harrison LH, et al. Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines. J Infect Dis. 2012;205(3):401-11.  https://doi.org/10.1093/infdis/jir755  PMID: 22158567 
  21. Isaacman DJ, McIntosh ED, Reinert RR. Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines. Int J Infect Dis. 2010;14(3):e197-209.  https://doi.org/10.1016/j.ijid.2009.05.010  PMID: 19700359 
  22. The council of the European Union. Council recommendation on stepping up EU actions to combat antimicrobial resistance in a One Health approach (2023/C 220/01). Official Journal of the European Union. 2023. Available from: https://data.europa.eu/doi/10.2875/636347
  23. Sciensano. Nationaal Referentiecentrum (NRC) voor Streptococcus pneumoniae (invasief). [National Reference Center (NRC) for Streptococcus pneumoniae (invasive)]. Flemish. Available from: https://www.sciensano.be/nl/nrc-nrl/nationaal-referentiecentrum-nrc-voor-streptococcus-pneumoniae-invasief
  24. Desmet S, Cuypers L. Report National Reference Centre invasive Streptococcus pneumoniae 2024. 2025. Available from: https://www.sciensano.be/sites/default/files/report_nrc_srpn_2024_v2.pdf
  25. Sciensano. Identificatie en karakterisering van de serogroep en serotype. Typering van de isolaten. [Identification and characterization of the serogroup and serotype. Typing of the isolates]. Ixelles: Sciensano. Flemish. Available from: https://www.sciensano.be/nl/analyse-aanvragen/identificatie-en-karakterisering-van-de-serogroep-en-serotype-typering-van-de-isolaten
  26. Sciensano. Gevoeligheid van stammen aan antibiotica. [Antibiotic susceptibility of strains]. Flemish]. Ixelles: Sciensano. [Accessed 11 Feb 2025]. Available from: https://www.sciensano.be/nl/analyse-aanvragen/gevoeligheid-van-stammen-aan-antibiotica
  27. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Clinical breakpoints and dosing of antibiotics. Version 14.0. Växjö: EUCAST; 2024. Available from: https://www.eucast.org/clinical_breakpoints
  28. R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. 2025. Available from: https://www.R-project.org/
  29. Desmet S, Cuypers L. Exceptional high number of invasive pneumococcal isolates for (December) 2024. Ixelles: Sciensano; 2025. Available from: https://www.sciensano.be/sites/default/files/communication_nrc_srpn_jan2025.pdf
  30. Desmet S, Cuypers L. Report National Reference Centre invasive Streptococcus pneumoniae 2023. Ixelles: Sciensano. 2024. Available from: https://www.sciensano.be/sites/default/files/report_nrc_srpn_2023_final.pdf
  31. Desmet S, Cuypers L. Report National Reference Centre Streptococcus pneumoniae 2022. Ixelles: Sciensano; 2023. Available from: https://www.sciensano.be/sites/default/files/report_nrc_srpn_2022_final_0.pdf
  32. Brueggemann AB, Jansen van Rensburg MJ, Shaw D, McCarthy ND, Jolley KA, Maiden MCJ, 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(6):e360-70.  https://doi.org/10.1016/S2589-7500(21)00077-7  PMID: 34045002 
  33. Shaw D, Abad R, Amin-Chowdhury Z, Bautista A, Bennett D, Broughton K, 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(9):e582-93.  https://doi.org/10.1016/S2589-7500(23)00108-5  PMID: 37516557 
  34. Willen L, Ekinci E, Cuypers L, Theeten H, Desmet S. Infant Pneumococcal Carriage in Belgium Not Affected by COVID-19 Containment Measures. Front Cell Infect Microbiol. 2022;11(January):825427.  https://doi.org/10.3389/fcimb.2021.825427  PMID: 35111700 
  35. European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance in the EU/EEA (EARS-Net) - Annual Epidemiological Report 2022. Stockholm: ECDC; 2023. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/AER-antimicrobial-resistance.pdf
  36. Liechti FD, Bijlsma MW, Brouwer MC, van Sorge NM, van de Beek D. Impact of the COVID-19 pandemic on incidence and serotype distribution of pneumococcal meningitis - A prospective, nationwide cohort study from the Netherlands. J Infect. 2024;88(1):65-7.  https://doi.org/10.1016/j.jinf.2023.11.002  PMID: 37949362 
  37. Waterlow NR, Cooper BS, Robotham JV, Knight GM. Antimicrobial resistance prevalence in bloodstream infection in 29 European countries by age and sex: An observational study. PLoS Med. 2024;21(3):e1004301.  https://doi.org/10.1371/journal.pmed.1004301  PMID: 38484006 
  38. Cillóniz C, Garcia-vidal C, Ceccato A, Torres A. Antimicrobial Resistance Among Streptococcus pneumoniae. In: Antimicrobial Resistance in the 21st Century, Emerging Infectious Diseases of the 21st Century. Springer International Publishing AG; 2018. p. 81. DOI:  https://doi.org/10.1007/978-3-319-78538-7 
  39. Kuster SP, Rudnick W, Shigayeva A, Green K, Baqi M, Gold WL, et al. , Toronto Invasive Bacterial Diseases Network. Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance. Clin Infect Dis. 2014;59(7):944-52.  https://doi.org/10.1093/cid/ciu497  PMID: 24973312 
  40. Romandini A, Pani A, Schenardi PA, Pattarino GAC, De Giacomo C, Scaglione F. Antibiotic resistance in pediatric infections: Global emerging threats, predicting the near future. Antibiotics (Basel). 2021;10(4):393.  https://doi.org/10.3390/antibiotics10040393  PMID: 33917430 
  41. Montanari MP, Cochetti I, Mingoia M, Varaldo PE. Phenotypic and molecular characterization of tetracycline- and erythromycin-resistant strains of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2003;47(7):2236-41.  https://doi.org/10.1128/AAC.47.7.2236-2241.2003  PMID: 12821474 
  42. Andrejko K, Ratnasiri B, Lewnard JA. Association of Pneumococcal Serotype With Susceptibility to Antimicrobial Drugs: A Systematic Review and Meta-analysis. Clin Infect Dis. 2022;75(1):131-40.  https://doi.org/10.1093/cid/ciab852  PMID: 34599811 
  43. Savrasova L, Villerusa A, Zeltina I, Krumina A, Cupeca H, Balasegaram S, et al. Streptococcus pneumoniae serotypes and factors associated with antimicrobial resistance in Invasive pneumococcal disease cases in Latvia, 2012-2022. Front Public Health. 2025;13(March):1501821.  https://doi.org/10.3389/fpubh.2025.1501821  PMID: 40145005 
  44. Loo JD, Conklin L, Fleming-Dutra KE, Knoll MD, Park DE, Kirk J, et al. Systematic review of the indirect effect of pneumococcal conjugate vaccine dosing schedules on pneumococcal disease and colonization. Pediatr Infect Dis J. 2014;33(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence) Supportin g Different Schedules;S161-71.  https://doi.org/10.1097/INF.0000000000000084  PMID: 24336058 
  45. Ilic A, Tort MJ, Cane A, Farkouh RA, Rozenbaum MH. The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US. Vaccines (Basel). 2024;12(11):1279.  https://doi.org/10.3390/vaccines12111279  PMID: 39591182 
  46. Fridh AC, Palmborg A, Ta A, Freigofaite D, Warren S, Perdrizet J. An economic evaluation of pneumococcal conjugate vaccines, PCV20 versus PCV15, for the prevention of pneumococcal disease in the Swedish pediatric population. Hum Vaccin Immunother. 2024;20(1):2400751.  https://doi.org/10.1080/21645515.2024.2400751  PMID: 39279284 
  47. Serrano-Mayorga CC, Ibáñez-Prada ED, Restrepo-Martínez JM, Garcia-Gallo E, Duque S, Severiche-Bueno DF, et al. The potential impact of PCV-13, PCV-15 and PCV-20 vaccines in Colombia. Vaccine. 2024;42(7):1435-9.  https://doi.org/10.1016/j.vaccine.2024.01.086  PMID: 38336559 
  48. Janssens E, Flamaing J, Vandermeulen C, Peetermans WE, Desmet S, De Munter P, Acta Clinica Belgica. The 20-valent pneumococcal conjugate vaccine (PCV20): expected added value. Acta Clin Belg. 2023;78(1):78-86.  https://doi.org/10.1080/17843286.2022.2039865  PMID: 35171752 
  49. Rozenbaum MH, Huang L, Cane A, Arguedas A, Chapman R, Dillon-Murphy D, et al. Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13. J Med Econ. 2024;27(1):644-52.  https://doi.org/10.1080/13696998.2024.2339638  PMID: 38577742 
  50. Dias SP, Brouwer MC, Bijlsma MW, van der Ende A, van de Beek D. Sex-based differences in pneumococcal serotype distribution in adults with pneumococcal meningitis. J Infect. 2016;73(6):616-9.  https://doi.org/10.1016/j.jinf.2016.08.009  PMID: 27567977 
  51. Passaris I, Depickère S, Braeye T, Mukovnikova M, Vodolazkaia A, Abels C, et al. , NIPD study group Belgium. Non-invasive Streptococcus pneumoniae infections are associated with different serotypes than invasive infections, Belgium, 2020 to 2023. Euro Surveill. 2024;29(45):2400108.  https://doi.org/10.2807/1560-7917.ES.2024.29.45.2400108  PMID: 39512163 
Higher valency vaccines’ impact on antimicrobial resistance rates in Streptococcus pneumoniae causing invasive disease: a retrospective analysis based on national reference laboratory data, Belgium, 2018 to 2023
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Helene+Vermeulen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Vermeulen Helene</a>, <a href="/search?value1=Lize+Cuypers&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Cuypers Lize</a>, <a href="/search?value1=Boudewijn+Catry&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Catry Boudewijn</a>, <a href="/search?value1=Stefanie+Desmet&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Desmet Stefanie</a>, <a href="/search?value1=Niel+Hens&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hens Niel</a></span>. Higher valency vaccines’ impact on antimicrobial resistance rates in Streptococcus pneumoniae causing invasive disease: a retrospective analysis based on national reference laboratory data, Belgium, 2018 to 2023. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(45):pii=2500179. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.45.2500179" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.45.2500179</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 07 Mar 2025;&nbsp;&nbsp; <span class="generated">Accepted</span>: 26 Jul 2025 </span> </p>
/content/10.2807/1560-7917.ES.2025.30.45.2500179
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