Serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease isolates from children in mainland China—a systematic review

  • Weidong Men
  • Qiaoli Dong
  • Wei Shi
  • Kaihu YaoEmail author
Clinical Microbiology - Review



This study aimed to review and report the serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease (IPD) isolates, as this information is important for policy making since China has not adopted any pneumococcal vaccines in the national immunization schedule.


A systematic review of the published literature from January 2000 to December 2018 was performed to identify articles that describe the serotype and/or antimicrobial resistance patterns of IPD cases in children in mainland China. Analysis of the extracted data was performed with the Microsoft Excel spreadsheet program. The percentage of the serotypes was calculated by dividing the number of isolates for each serotype with the total number of isolates included in all the studies. The theoretical impact of the vaccine was estimated by calculating the percentage of isolates that exhibited the serotypes included in the vaccines. The prevalence of antimicrobial resistance was defined as the number of isolates that were resistant divided by the total number of isolates tested for resistance to the specific antimicrobial agent.


Forty-two articles were screened in the preliminary search, of which sixteen fulfilled inclusion criteria and were included in the final analysis. The predominant serotypes were 19A, 19F, 14, 23F, and 6B, and the estimated impact of PCV13 was 90.4%. The isolates exhibited a high frequency of resistance to cefuroxime, cefaclor, and erythromycin.


It is necessary for Chinese children to receive PCV13. Clinical workers should pay attention to the high frequency of resistance to antimicrobial agents.


Antibiotic resistance Children Invasive pneumococcal disease Pneumococcal conjugate vaccine Serotype 



  1. 1.
    World Health Organization (2019) WHO vaccine-preventable diseases: monitoring system. 2018 global summary. 2018; Accessed 01 April 2019
  2. 2.
    Whitney CG, Pilishvili T, Farley MM, Schaffner W, Craig AS, Lynfield R, Nyquist AC, Gershman KA, Vazquez M, Bennett NM, Reingold A, Thomas A, Glode MP, Zell ER, Jorgensen JH, Beall B, Schuchat A (2006) Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study. Lancet 368:1495–1502PubMedCrossRefGoogle Scholar
  3. 3.
    Weatherholtz R, Millar EV, Moulton LH, Reid R, Rudolph K, Santosham M, O’Brien KL (2010) Invasive pneumococcal disease a decade after pneumococcal conjugate vaccine use in an American Indian population at high risk for disease. Clin Infect Dis 50:1238–1246CrossRefGoogle Scholar
  4. 4.
    Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, Reingold A, Thomas A, Schaffner W, Craig AS, Smith PJ, Beall BW, Whitney CG, Moore MR, Active Bacterial Core Surveillance/Emerging Infections Program Network (2010) Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 201:32–41PubMedCrossRefGoogle Scholar
  5. 5.
    Moore MR, Link-Gelles R, Schaffner W, Lynfield R, Holtzman C, Harrison LH, Zansky SM, Rosen JB, Reingold A, Scherzinger K, Thomas A, Guevara RE, Motala T, Eason J, Barnes M, Petit S, Farley MM, McGee L, Jorgensen JH, Whitney CG (2016) Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study. Lancet Respir Med 4:399–406CrossRefGoogle Scholar
  6. 6.
    Cohen C, von Mollendorf C, de Gouveia L, Lengana S, Meiring S, Quan V et al (2017) Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South Africa children: a case-control study. Lancet Glob Health 5:e359–e369PubMedCrossRefGoogle Scholar
  7. 7.
    Kambiré D, Soeters HM, Ouédraogo-Traoré R, Medah I, Sangaré L, Yaméogo I et al (2018) Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis-Burkina Faso, 2014-2015. J Inf Secur 76:270–279Google Scholar
  8. 8.
    Whitney CG (2018) Examining duration of protection: should a booster dose be part of all infant pneumococcal conjugate vaccine programs? Clin Infect Dis 67:375–377CrossRefGoogle Scholar
  9. 9.
    Kent A, Makwana A, Sheppard CL, Collins S, Fry NK, Heath PT, Ramsay M, Ladhani SN (2019) Invasive pneumococcal disease in UK children under 1 year of age in the post-PCV13 era: what are the risks now? Clin Infect Dis 69:84–90PubMedCrossRefGoogle Scholar
  10. 10.
    Arushothy R, Ahmad N, Amran F, Hashim R, Samsudin N, Azih CRC (2019) Pneumococcal serotype distribution and antibiotic susceptibility in Malaysia: a four-year study (2014-2017) on invasive paediatric isolates. Int J Infect Dis 80:129–133CrossRefGoogle Scholar
  11. 11.
    Perniciaro S, Imöhl M, Fitzner C, van der Linden M (2019) Regional variations in serotype distribution and vaccination status in children under six years of age with invasive pneumococcal disease in Germany. PLoS One 14(1):e0210278PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Stephens DS, Zughaier SM, Whitney CG, Baughman WS, Barker L, Gay K, Jackson D, Orenstein WA, Arnold K, Schuchat A, Farley MM, Georgia Emerging Infections Program (2005) Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment. Lancet 365:855–863PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    von Gottberg A, de Gouveia L, Tempia S, Quan V, Meiring S, von Mollendorf C et al (2014) Effects of vaccination on invasive pneumococcal disease in South Africa. N Engl J Med 371:1889–1899CrossRefGoogle Scholar
  14. 14.
    Kim L, McGee L, Tomczyk S, Beall B (2016) Biological and epidemiological features of antibiotic-resistant Streptococcus pneumoniae in pre- and post-conjugate vaccine eras: a United States perspective. Clin Microbiol Rev 29:525–552PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Schroeder MR, Chancey ST, Thomas S, Kuo WH, Satola SW, Farley MM, Stephens DS (2017) A population-based assessment of the impact of 7- and 13-valent pneumococcal conjugate vaccines on macrolide-resistant invasive pneumococcal disease: emergence and decline of Streptococcus pneumoniae serotype 19A (CC320) with dual macrolide resistance mechanisms. Clin Infect Dis 65:990–998PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Zheng JS, Cao L, Guo SC, A KZ, Wang L, Yu WZ et al (2012) Survey on the immunization status of category B vaccine among children aged 1 to 2 years in China. Chin J Vaccine Immunization 18:233–237 (in Chinese)Google Scholar
  17. 17.
    Xue L, Yao K, Xie G, Zheng Y, Wang C, Shang Y, Wang H, Wan L, Liu L, Li C, Ji W, Xu X, Wang Y, Xu P, Liu Z, Yu S, Yang Y (2010) Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates that cause invasive disease among Chinese children. Clin Infect Dis 50:741–744PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Kan QC, Wen JG, Liu XH, Li ZZ (2016) Inappropriate use of antibiotics in children in China. Lancet 387:1273–1274CrossRefGoogle Scholar
  19. 19.
    Yao KH, Wang LB, Zhao GM, Zheng YJ, Deng L, Huang JF, Wang JX, Zhao RZ, Deng QL, Hu YH, Yu SJ, Yang YH, Young M (2011) Pneumococcal serotype distribution and antimicrobial resistance in Chinese children hospitalized for pneumonia. Vaccine 29:2296–2301PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Zhou X, Liu J, Zhang Z, Liu Y, Wang Y, Liu Y (2016) Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China. Eur J Clin Microbiol Infect Dis 35:633–645PubMedCrossRefGoogle Scholar
  21. 21.
    Xu F, Chi FL, Tan H, Liu XM, Cao T, Pan W et al (2012) Study on serotype distribution in 48 isolates of invasive Streptococcus pneumoniae with which children infected. Chin J Biochem Pharm 33:909–912 (in Chinese)Google Scholar
  22. 22.
    Lu C (2015) Investigation on serotype distribution of invasive pneumococcal disease isolates from children. Int J Lab Med 36:990–992 (in Chinese)Google Scholar
  23. 23.
    Zhou K, Xie GJ, Wang XW, Xu F, Yao KH (2015) Clinical characteristics of invasive pneumococcal disease and its serotype distribution. Chin J Nosocomiol 25:3392–3394 (in Chinese)Google Scholar
  24. 24.
    Wang J, Liu F, Ao P, Li X, Zheng H, Wu D et al (2017) Detection of serotype distribution and drug resistance of Streptococcus pneumoniae isolated from pediatric patients. Lab Med 48:39–45PubMedCrossRefGoogle Scholar
  25. 25.
    Shi W, Li J, Dong F, Qian S, Liu G, Xu B, Zhou L, Xu W, Meng Q, Wang Q, Shen K, Ma L, Yao K (2019) Serotype distribution, antibiotic resistance pattern, and multilocus sequence types of invasive Streptococcus pneumoniae isolates in two tertiary pediatric hospitals in Beijing prior to PCV13 availability. Expert Rev Vaccines 18:89–94PubMedCrossRefGoogle Scholar
  26. 26.
    Ma X, Zhao R, Ma Z, Yao K, Yu S, Zheng Y et al (2013) Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates causing invasive diseases from Shenzhen Children’s Hospital. PLoS One 8:e67507PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Liu Y, Wang H, Chen M, Sun Z, Zhao R, Zhang L et al (2008) Serotype distribution and antimicrobial resistance patterns of Streptococcus pneumoniae isolated from children in China younger than 5 years. Diagn Microbiol Infect Dis 61:256–263PubMedCrossRefGoogle Scholar
  28. 28.
    Wang Q, Wu J, Liu J, Dong F, Yao KH, Shen KL et al (2016) Clinical features and outcomes of invasive pneumococcal disease in pediatric intensive care unit. Chin J Appl Clin Pediatr 31:1400–1404 (in Chinese)Google Scholar
  29. 29.
    Cai K, Wang Y, Guo Z, Xu X, Li H, Zhang Q (2018) Clinical characteristics and antimicrobial resistance of pneumococcal isolates of pediatric invasive pneumococcal disease in China. Infect Drug Resist 11:2461–2469PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Su M, Chang L, Zhou W, Mu LY, Kuang LH (2015) Clinical characteristics of children with meningitis caused by Streptococcus pneumoniae and antibiotic resistance of Streptococcus pneumoniae strains. Chin J Contemp Pediatr 17:706–709 (in Chinese)Google Scholar
  31. 31.
    Zou ZP (2015) Clinical features and antimicrobial resistance patterns of 102 pediatric cases with invasive pneumococcal disease. Shenzhen J Integr Tradit Chin W Med 25:188–190 (in Chinese)Google Scholar
  32. 32.
    Wang HM, Ma DL, Quan JL, Huang BX, Zhao RZ, Chen HY (2012) Drug-resistance of Streptococcus pneumoniae isolated from children. Chin J Infect Control 11(221–222):220 (in Chinese)Google Scholar
  33. 33.
    Zhang TD, Kong Q, Wang C, Qin HH, Zhang H (2014) Resistant mechanism of β-lactam antibiotic of invasive Streptococcus pneumoniae. Chin J Lab Med 37:748–752 (in Chinese)Google Scholar
  34. 34.
    Wang ML, Yan YD, Huang L, Zhu CH, Wang YQ, Chen ZR et al (2012) Clinical features and antimicrobial resistance of invasive pneumococcal disease in 38 children. Chin J Pract Pediatr 27:604–607 (in Chinese)Google Scholar
  35. 35.
    Lyu S, Hu HL, Yang YH, Yao KH (2017) A systematic review about Streptococcus pneumoniae serotype distribution in children in mainland of China before the PCV13 was licensed. Expert Rev Vaccines 16:997–1006PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Chen K, Zhang X, Shan W, Zhao G, Zhang T (2018) Serotype distribution of Streptococcus pneumoniae and potential impact of pneumococcal conjugate vaccines in China: a systematic review and meta-analysis. Hum Vaccin Immunother 14:1453–1463PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Jyotsana Singh J, Sundaresan S, Manoharan A, Shet A (2017) Serotype distribution and antimicrobial susceptibility pattern in children ≤ 5 years with invasive pneumococcal disease in India-a systematic review. Vaccine 35:4501–4509PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Johnson HL, Deloria-Knoll M, Levine OS, Stoszek SK, Freimanis Hance L, Reithinger R et al (2010) Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med 7:e1000348PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Jaiswal N, Singh M, Das RR, Jindal I, Agarwal A, Thumburu KK et al (2014) Distribution of serotypes, vaccine coverage, and antimicrobial susceptibility pattern of Streptococcus pneumoniae in children living in SAARC countries: asystematic review. PLoS One 9:e108617PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Harboe ZB, Dalby T, Weinberger DM, Benfield T, Mølbak K, Slotved HC et al (2014) Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumoccal disease incidence and mortality. Clin Infect Dis 59:1066–1073PubMedCrossRefGoogle Scholar
  41. 41.
    Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MP, Miller E (2015) Effect of the 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis 15:535–543PubMedCrossRefGoogle Scholar
  42. 42.
    Mackenzie GA, Hill PC, Jeffries DJ, Hossain I, Uchendu U, Ameh D, Ndiaye M, Adeyemi O, Pathirana J, Olatunji Y, Abatan B, Muhammad BS, Fombah AE, Saha D, Plumb I, Akano A, Ebruke B, Ideh RC, Kuti B, Githua P, Olutunde E, Ofordile O, Green E, Usuf E, Badji H, Ikumapayi UNA, Manjang A, Salaudeen R, Nsekpong ED, Jarju S, Antonio M, Sambou S, Ceesay L, Lowe-Jallow Y, Jasseh M, Mulholland K, Knoll M, Levine OS, Howie SR, Adegbola RA, Greenwood BM, Corrah T (2016) Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis 16:703–711PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Lehmann D, Willis J, Moore HC, Giele C, Murphy D, Keil AD, Harrison C, Bayley K, Watson M, Richmond P (2010) The changing epidemiology of invasive pneumococcal disease in aboriginal and non-aboriginal western Australians from 1997 through 2007 and emergence of nonvaccine serotypes. Clin Infect Dis 50:1477–1486PubMedCrossRefGoogle Scholar
  44. 44.
    Miller E, Andrews NJ, Waight PA, Slack MP, George RC (2011) 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):760–768CrossRefGoogle Scholar
  45. 45.
    Knol MJ, Wagenvoort GHJ, Sanders EAM, Elberse K, Vlaminckx BJ, de Melker HE et al (2015) Invasive pneumococcal disease 3 years after introduction of 10-valent pneumococcal conjugate vaccine, the Netherlands. Emerg Infect Dis 2015(21):2040–2044CrossRefGoogle Scholar
  46. 46.
    Galanis I, Lindstrand A, Darenberg J, Browall S, Nannapaneni P, Sjöström K et al (2016) Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden. Eur Respir J 2016(47):1208–1218CrossRefGoogle Scholar
  47. 47.
    Clinical and Laboratory Standards Institute (CLSI) (2006) Performance standards for antimicrobial susceptibility testing; 20th informational supplement. Clinical and Laboratory Standards Institute, Wayne, pp M100–MS16Google Scholar
  48. 48.
    Clinical and Laboratory Standards Institute (CLSI) (2010) Performance standards for antimicrobial susceptibility testing; 20th informational supplement. Clinical and Laboratory Standards Institute, Wayne, pp M100–MS20Google Scholar
  49. 49.
    Kim SH, Song JH, Chung DR, Thamlikitkul V, Yang Y, Wang H et al (2012) Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study. Antimicrob Agents Chemother 56:1418–1426PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Sociedade Brasileira de Microbiologia 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryAffiliated Hospital of Hebei UniversityBaodingChina
  2. 2.Department of PediatricsAffiliated Hospital of Hebei UniversityBaodingChina
  3. 3.Beijing Pediatric Research Institute, Beijing Children’s HospitalCapital Medical University, National Center for Children’s HealthBeijingChina

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