Research article Open Access
Like 0


Conjugate vaccines have reduced pneumococcal disease in vaccinated children and unvaccinated adults, but non-vaccine serotypes are of concern, particularly if antibiotic resistant. We reviewed collected via: (i) the British Society for Antimicrobial Chemotherapy (BSAC) surveillances from 2001–2014; (ii) Public Health England’s (PHE) invasive isolate surveillance from 2005–2014 and (iii) referral to PHE for resistance investigation from 2005–2014. Serotype 15A increased in all series, with many representatives showing triple resistance to macrolides, tetracyclines and penicillin. 15A was consistently among the 10 most prevalent serotypes from 2011 in PHE and BSAC invasive isolate/bacteraemia surveillance but never previously; 26–33% of these invasive 15A isolates had triple resistance. BSAC respiratory isolates were only serotyped in 2013/14 and 2014/15 (October to September); 15A was most prevalent serotype in both periods, comprising 9–11% of isolates, 38–48% of them with triple resistance. Serotype 15A represented 0–4% of referred to PHE for reference investigation annually until 2008 but rose to 29% (2013) and 32% (2014). Almost all multidrug-resistant 15A isolates were sequence type (ST) 63 variants, whereas susceptible 15A isolates were clonally diverse. The rise of serotype 15A suggests that pneumococcal conjugate vaccines will need ongoing adaptation.


Article metrics loading...

Loading full text...

Full text loading...



  1. Isaacman DJ, Fletcher MA, Fritzell B, Ciuryla V, Schranz J. Indirect effects associated with widespread vaccination of infants with heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar). Vaccine. 2007;25(13):2420-7.  https://doi.org/10.1016/j.vaccine.2006.09.011  PMID: 17049677 
  2. Rodrigo C, Bewick T, Sheppard C, Greenwood S, Macgregor V, Trotter C, et al. Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status. Thorax. 2014;69(2):168-73.  https://doi.org/10.1136/thoraxjnl-2013-203987  PMID: 24048505 
  3. Myint TT, Madhava H, Balmer P, Christopoulou D, Attal S, Menegas D, et al. The impact of 7-valent pneumococcal conjugate vaccine on invasive pneumococcal disease: a literature review. Adv Ther. 2013;30(2):127-51.  https://doi.org/10.1007/s12325-013-0007-6  PMID: 23397399 
  4. Isaacman DJ, Strutton DR, Kalpas EA, Horowicz-Mehler N, Stern LS, Casciano R, et al. The impact of indirect (herd) protection on the cost-effectiveness of pneumococcal conjugate vaccine. Clin Ther. 2008;30(2):341-57.  https://doi.org/10.1016/j.clinthera.2008.02.003  PMID: 18343273 
  5. Song JH, Dagan R, Klugman KP, Fritzell B. The relationship between pneumococcal serotypes and antibiotic resistance. Vaccine. 2012;30(17):2728-37.  https://doi.org/10.1016/j.vaccine.2012.01.091  PMID: 22330126 
  6. Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008;8(12):785-95.  https://doi.org/10.1016/S1473-3099(08)70281-0  PMID: 19022193 
  7. Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis. 2011;11(10):760-8.  https://doi.org/10.1016/S1473-3099(11)70090-1  PMID: 21621466 
  8. Henderson KL, Muller-Pebody B, Blackburn RM, Johnson AP. Reduction in erythromycin resistance in invasive pneumococci from young children in England and Wales. J Antimicrob Chemother. 2010;65(2):369-70.  https://doi.org/10.1093/jac/dkp442  PMID: 20007730 
  9. Clarke SC, Scott KJ, McChlery SM. Erythromycin resistance in invasive serotype 14 pneumococci is highly related to clonal type. J Med Microbiol. 2004;53(Pt 11):1101-3.  https://doi.org/10.1099/jmm.0.45737-0  PMID: 15496387 
  10. Reinert R, Jacobs MR, Kaplan SL. Pneumococcal disease caused by serotype 19A: review of the literature and implications for future vaccine development. Vaccine. 2010;28(26):4249-59.  https://doi.org/10.1016/j.vaccine.2010.04.020  PMID: 20416266 
  11. Liñares J, Ardanuy C, Pallares R, Fenoll A. Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period. Clin Microbiol Infect. 2010;16(5):402-10.  https://doi.org/10.1111/j.1469-0691.2010.03182.x  PMID: 20132251 
  12. van Hoek AJ, Sheppard CL, Andrews NJ, Waight PA, Slack MP, Harrison TG, et al. Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England. Vaccine. 2014;32(34):4349-55.  https://doi.org/10.1016/j.vaccine.2014.03.017  PMID: 24657717 
  13. Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MP, Miller E. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis. 2015;15(5):535-43.  https://doi.org/10.1016/S1473-3099(15)70044-7  PMID: 25801458 
  14. Ozawa D, Yano H, Endo S, Hidaka H, Kakuta R, Okitsu N, et al. Impact of the Seven-valent Pneumococcal Conjugate Vaccine on Acute Otitis Media in Japanese Children: Emergence of Serotype 15A Multidrug-resistant Streptococcus pneumoniae in Middle Ear Fluid Isolates. Pediatr Infect Dis J. 2015;34(9):e217-21.  https://doi.org/10.1097/INF.0000000000000776  PMID: 26083590 
  15. Suga S, Chang B, Asada K, Akeda H, Nishi J, Okada K, et al. Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine. Vaccine. 2015;33(45):6054-60.  https://doi.org/10.1016/j.vaccine.2015.07.069  PMID: 26235372 
  16. Ho PL, Chiu SS, Law PY, Chan EL, Lai EL, Chow KH. Increase in the nasopharyngeal carriage of non-vaccine serogroup 15 Streptococcus pneumoniae after introduction of children pneumococcal conjugate vaccination in Hong Kong. Diagn Microbiol Infect Dis. 2015;81(2):145-8.  https://doi.org/10.1016/j.diagmicrobio.2014.11.006  PMID: 25483278 
  17. Richter SS, Diekema DJ, Heilmann KP, Dohrn CL, Riahi F, Doern GV. Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the United States. Antimicrob Agents Chemother. 2014;58(11):6484-9.  https://doi.org/10.1128/AAC.03344-14  PMID: 25136018 
  18. Golden AR, Adam HJ, Gilmour MW, Baxter MR, Martin I, Nichol KA, et al. Assessment of multidrug resistance, clonality and virulence in non-PCV-13 Streptococcus pneumoniae serotypes in Canada, 2011-13. J Antimicrob Chemother. 2015;70(7):1960-4. PMID: 25761605 
  19. Steens A, Bergsaker MA, Aaberge IS, Rønning K, Vestrheim DF. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. Vaccine. 2013;31(52):6232-8.  https://doi.org/10.1016/j.vaccine.2013.10.032  PMID: 24176490 
  20. Mameli C, Fabiano V, Daprai L, Bedogni G, Faccini M, Garlaschi ML, et al. A longitudinal study of streptococcus pneumoniae carriage in healthy children in the 13-valent pneumococcal conjugate vaccine era. Hum Vaccin Immunother. 2015;11(4):811-7.  https://doi.org/10.1080/21645515.2015.1010945  PMID: 25751237 
  21. Strachan JE, Rowe SL, Dunne EM, Hogg GG. Emergence of Streptococcus pneumoniae serotype 15A after the introduction of the conjugate vaccine in Victoria. Med J Aust. 2013;199(7):461-3.  https://doi.org/10.5694/mja13.10420  PMID: 24099202 
  22. British Society for Antimicrobial Chemotherapy (BSAC) Resistance Surveillance Project. [Accessed 15 July 2016]. Available from: http://www.bsacsurv.org/
  23. Reynolds R, Hope R, Williams LBSAC Working Parties on Resistance Surveillance. Survey, laboratory and statistical methods for the BSAC Resistance Surveillance Programmes. J Antimicrob Chemother. 2008;62(Suppl 2):ii15-28.  https://doi.org/10.1093/jac/dkn349  PMID: 18819976 
  24. Farrell DJ, Felmingham D, Shackcloth J, Williams L, Maher K, Hope R, et al. BSAC Working Parties on Resistance Surveillance. Non-susceptibility trends and serotype distributions among Streptococcus pneumoniae from community-acquired respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to 2007. J Antimicrob Chemother. 2008;62(Suppl 2):ii87-95.  https://doi.org/10.1093/jac/dkn355  PMID: 18819983 
  25. European Antimicrobial Resistance Surveillance Network (EARS-Net). [Accessed 15 July 2016]. Available from: http://ecdc.europa.eu/en/healthtopics/antimicrobial-resistance-and-consumption/antimicrobial_resistance/EARS-Net/Pages/EARS-Net.aspx
  26. Lund E, Henrichsen J. Laboratory diagnosis, serology and epidemiology of Streptococcus pneumoniae. In: T. Bergan and J. R. Norris, editors. Methods in Microbiology. London: Academic Press; 1978. p. 241-262.
  27. [No authors listed]. A guide to sensitivity testing. Report of the Working Party on Antibiotic Sensitivity Testing of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 1991;27 Suppl D:1-50.
  28. The European Committee on Antimicrobial Susceptibility Testing - EUCAST. [Accessed Accessed 15 July 2016]. Available from: http://www.eucast.org/
  29. Public databases for molecular typing and microbial genome diversity (PubMLST). Streptococcus pneumonia MLST Databases. Oxford: Department of Zoology, University of Oxford. [Accessed 27 Feb 2016]. Available from: http://pubmlst.org/spneumoniae/
  30. Inouye M, Conway TC, Zobel J, Holt KE. Short read sequence typing (SRST): multi-locus sequence types from short reads. BMC Genomics. 2012;13(1):338.  https://doi.org/10.1186/1471-2164-13-338  PMID: 22827703 
  31. Arguedas A, Soley C, Abdelnour A. Prevenar experience. Vaccine. 2011;29(Suppl 3):C26-34.  https://doi.org/10.1016/j.vaccine.2011.06.104  PMID: 21896350 
  32. Koshy E, Murray J, Bottle A, Sharland M, Saxena S. Impact of the seven-valent pneumococcal conjugate vaccination (PCV7) programme on childhood hospital admissions for bacterial pneumonia and empyema in England: national time-trends study, 1997-2008. Thorax. 2010;65(9):770-4.  https://doi.org/10.1136/thx.2010.137802  PMID: 20805169 
  33. Ansaldi F, Sticchi L, Durando P, Carloni R, Oreste P, Vercelli M, et al. Decline in pneumonia and acute otitis media after the introduction of childhood pneumococcal vaccination in Liguria, Italy. J Int Med Res. 2008;36(6):1255-60.  https://doi.org/10.1177/147323000803600612  PMID: 19094434 
  34. Fortanier AC, Venekamp RP, Boonacker CW, Hak E, Schilder AG, Sanders EA, et al. Pneumococcal conjugate vaccines for preventing otitis media. Cochrane Database Syst Rev. 2014;4(4):CD001480. PMID: 24696098 
  35. Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-25.  https://doi.org/10.1056/NEJMoa1408544  PMID: 25785969 
  36. Naito S, Tanaka J, Nagashima K, Chang B, Hishiki H, Takahashi Y, et al. The impact of heptavalent pneumococcal conjugate vaccine on the incidence of childhood community-acquired pneumonia and bacteriologically confirmed pneumococcal pneumonia in Japan. Epidemiol Infect. 2016;144(3):494-506.  https://doi.org/10.1017/S0950268815001272  PMID: 26122538 
  37. van der Linden M, Perniciaro S, Imöhl M. Increase of serotypes 15A and 23B in IPD in Germany in the PCV13 vaccination era. BMC Infect Dis. 2015;15(1):207.  https://doi.org/10.1186/s12879-015-0941-9  PMID: 25940580 
  38. Frazão N, Hiller NL, Powell E, Earl J, Ahmed A, Sá-Leão R, et al. Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine. PLoS One. 2013;8(9):e74867.  https://doi.org/10.1371/journal.pone.0074867  PMID: 24069360 
  39. Ardanuy C, de la Campa AG, García E, Fenoll A, Calatayud L, Cercenado E, et al. Spread of Streptococcus pneumoniae serotype 8-ST63 multidrug-resistant recombinant Clone, Spain. Emerg Infect Dis. 2014;20(11):1848-56.  https://doi.org/10.3201/eid2011.131215  PMID: 25340616 
  40. Sanz JC, Cercenado E, Marín M, Ramos B, Ardanuy C, Rodríguez-Avial I, et al. Multidrug-resistant pneumococci (serotype 8) causing invasive disease in HIV+ patients. Clin Microbiol Infect. 2011;17(7):1094-8.  https://doi.org/10.1111/j.1469-0691.2011.03495.x  PMID: 21463396 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error