Skip to main content

Dynamic changes in otopathogens colonizing the nasopharynx and causing acute otitis media in children after 13-valent (PCV13) pneumococcal conjugate vaccination during 2015–2019

European Journal of Clinical Microbiology & Infectious Diseases volume 41, pages 37–44 (2022)Cite this article

Abstract

The otopathogens colonizing the nasopharynx (NP) and causing acute otitis media (AOM) have shown dynamic changes following introduction of pneumococcal conjugate vaccines. Five hundred eighty-nine children were prospectively enrolled, 2015–2019. Two thousand fifty-nine visits (1528 healthy, 393 AOM, and 138 AOM follow-up) were studied. Two thousand forty-two NP and 495 middle ear fluid (MEF) samples by tympanocentesis from 319 AOM cases were cultured for bacterial identification and antibiotic susceptibility. Streptococcus pneumoniae (Spn) isolates were serotyped by Quellung, and multi-locus sequence type (ST) determined by genomic analysis. Haemophilus influenzae (Hi) was the most common otopathogen cultured from MEF during AOM (34% in MEF) followed by Spn (24% in MEF), then Moraxella catarrhalis (Mcat) (15% in MEF). NP isolates during healthy visit were Mcat (39%), Spn (32%), Hi (12%). 48.6% of Hi isolates from MEF were beta-lactamase-producing. Spn non-susceptibility to penicillin and other antibiotics was high. The most common Spn serotypes associated with AOM (and colonizing the NP during healthy visits) were 35B, 23B, and 15B/C. ST558 and ST199 were the most common sequence types. During 2015–2019, Hi was the most common otopathogen cultured from MEF during AOM among young children. Pneumococcal AOM was most commonly caused by non-PCV13 serotypes of Spn, predominantly 35B, 23B, and 15B/C. Resistance to common antibiotics among Spn strains showed an increasing trend.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1

adapted from a previous publication by our group [30]

Data availability

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

Code availability

N/A

References

  1. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y (1997) Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics. J Infect Dis 175(6):1440–1445

    CAS  Article  Google Scholar 

  2. Casey JR, Adlowitz DG, Pichichero ME (2010) New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J 29(4):304–309

    Article  Google Scholar 

  3. Casey JR, Kaur R, Friedel VC, Pichichero ME (2013) Acute otitis media otopathogens during 2008 to 2010 in Rochester, New York. Pediatr Infect Dis J 32(8):805–809

    Article  Google Scholar 

  4. Kaur R, Casey JR, Pichichero ME (2016) Emerging Streptococcus pneumoniae strains colonizing the nasopharynx in children after 13-valent pneumococcal conjugate vaccination in comparison to the 7-valent era, 2006–2015. Pediatr Infect Dis J 35(8):901–906

    Article  Google Scholar 

  5. Kaur R, Pham M, Yu KOA, Pichichero ME (2020) Rising pneumococcal antibiotic resistance in the post 13-valent pneumococcal conjugate vaccine era in pediatric isolates from a primary care setting. Clin Infect Dis 72(5):797–805

  6. Casey JR, Pichichero ME (2004) Changes in frequency and pathogens causing acute otitis media in 1995–2003. Pediatr Infect Dis J 23(9):824–828

    Article  Google Scholar 

  7. Pichichero ME, Casey JR (2007) Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA 298(15):1772–1778

    CAS  Article  Google Scholar 

  8. Clinical and Laboratory Standards Institute (2007) M100-performance standards for antimicrobial susceptibility testing. Seventeenth Informational Supplement. CLSI, Wayne, PA, pp 126–128

  9. Jolley KA, Bray JE, Maiden MCJ (2018) Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 24(3):124

  10. Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M, Carrico JA (2012) PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13:87

    Article  Google Scholar 

  11. Levy C, Varon E, Ouldali N, Wollner A, Thollot F, Corrard F, Werner A, Bechet S, Bonacorsi S, Cohen R (2019) Bacterial causes of otitis media with spontaneous perforation of the tympanic membrane in the era of 13 valent pneumococcal conjugate vaccine. PLoS One 14(2):e0211712

    CAS  Article  Google Scholar 

  12. Rybak A, Levy C, Bonacorsi S, Bechet S, Vie le Sage F, Elbez A, Varon E, Cohen R (2018) Antibiotic resistance of potential otopathogens isolated from nasopharyngeal flora of children with acute otitis media before, during and after pneumococcal conjugate vaccines implementation. Pediatr Infect Dis J 37(3):e72–e78

    Article  Google Scholar 

  13. Takeuchi N, Naito S, Ohkusu M, Abe K, Shizuno K, Takahashi Y, Omata Y, Nakazawa T, Takeshita K, Hishiki H, Hoshino T, Sato Y, Ishiwada N (2020) Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan. Epidemiol Infect 148:e91

    CAS  Article  Google Scholar 

  14. Zhang Z, Chen M, Yu Y, Pan S, Liu Y (2019) Antimicrobial susceptibility among Streptococcus pneumoniae and Haemophilus influenzae collected globally between 2015 and 2017 as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Infect Drug Resist 12:1209–1220

    CAS  Article  Google Scholar 

  15. Kaplan SL, Center KJ, Barson WJ, Ling-Lin P, Romero JR, Bradley JS, Tan TQ, Hoffman JA, Peters TR, Gurtman A, Scott DA, Trammel J, Gruber WC, Hulten KG, Mason EO (2015) Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Dis  60(9):1339–1345

    PubMed  Google Scholar 

  16. Quirk SJ, Haraldsson G, Erlendsdottir H, Hjalmarsdottir MA, van Tonder AJ, Hrafnkelsson B, Sigurdsson S, Bentley SD, Haraldsson A, Brueggemann AB, Kristinsson KG (2018) Effect of vaccination on pneumococci isolated from the nasopharynx of healthy children and the middle ear of children with otitis media in Iceland. J Clin Microbiol 27;56 (12):e01046–18

  17. Olarte L, Barson WJ, Barson RM, Lin PL, Romero JR, Tan TQ, Givner LB, Bradley JS, Hoffman JA, Hulten KG, Mason EO, Kaplan SL (2015) Impact of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis  61(5):767–775

    Article  Google Scholar 

  18. Pichichero M, Kaur R, Scott DA, Gruber WC, Trammel J, Almudevar A, Center KJ (2018) Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study. Lancet Child Adolesc Health 2(8):561–568

    Article  Google Scholar 

  19. Morales M, Ludwig G, Ercibengoa M, Esteva C, Sanchez-Encinales V, Alonso M, Munoz-Almagro C, Marimon JM (2018) Changes in the serotype distribution of Streptococcus pneumoniae causing otitis media after PCV13 introduction in Spain. PLoS One 13(12):e0209048

    Article  Google Scholar 

  20. Lee GM, Kleinman K, Pelton S, Lipsitch M, Huang SS, Lakoma M, Dutta-Linn M, Rett M, Hanage WP, Finkelstein JA (2017) Immunization, antibiotic use, and pneumococcal colonization over a 15-year period. Pediatrics 140(5):e20170001

    Article  Google Scholar 

  21. Kaplan SL, Barson WJ, Lin PL, Romero JR, Bradley JS, Tan TQ, Pannaraj PS, Givner LB, Hulten KG (2019) Invasive pneumococcal disease in children’s hospitals: 2014–2017. Pediatrics 144(3):e20190567

    Article  Google Scholar 

  22. Ben-Shimol S, Givon-Lavi N, Greenberg D, Dagan R (2016) Pneumococcal nasopharyngeal carriage in children <5 years of age visiting the pediatric emergency room in relation to PCV7 and PCV13 introduction in southern Israel. Hum Vaccin Immunother 12(2):268–276

    Article  Google Scholar 

  23. Ben-Shimol S, Givon-Lavi N, Greenberg D, van der Beek BA, Leibovitz E, Dagan R (2020) Substantial reduction of antibiotic-non-susceptible pneumococcal otitis media following PCV7/PCV13 sequential introduction. J Antimicrob Chemother 75(10):3038–3045

    CAS  Article  Google Scholar 

  24. Sheppard CL, Groves N, Andrews N, Litt DJ, Fry NK, Southern J, Miller E (2019) The genomics of Streptococcus pneumoniae carriage isolates from UK children and their household contacts, pre-PCV7 to post-PCV13. Genes (Basel) 10(9):687

  25. Azarian T, Mitchell PK, Georgieva M, Thompson CM, Ghouila A, Pollard AJ, von Gottberg A, du Plessis M, Antonio M, Kwambana-Adams BA, Clarke SC, Everett D, Cornick J, Sadowy E, Hryniewicz W, Skoczynska A, Moisi JC, McGee L, Beall B, Metcalf BJ, Breiman RF, Ho PL, Reid R, O’Brien KL, Gladstone RA, Bentley SD, Hanage WP (2018) Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathog 14(11):e1007438

    Article  Google Scholar 

  26. Kaur R, Czup K, Casey JR, Pichichero ME (2014) Correlation of nasopharyngeal cultures prior to and at onset of acute otitis media with middle ear fluid cultures. BMC Infect Dis 14:640

    Article  Google Scholar 

  27. Christensen ED, Thorsen J, Stokholm J, Pedersen TM, Brix S, Krogfelt KA, Schjorring S, Chawes B, Bonnelykke K, Bisgaard H, Rasmussen MA (2020) Early life bacterial airway colonization, local immune mediator response and risk of otitis media. J Med Microbiol 69(8):1124–1131

    CAS  Article  Google Scholar 

  28. Marchisio P, Esposito S, Picca M, Baggi E, Terranova L, Orenti A, Biganzoli E, Principi N, Milan AOMSG (2017) Prospective evaluation of the aetiology of acute otitis media with spontaneous tympanic membrane perforation. Clin Microbiol Infect 23(7):486 e481–486.e6

  29. Khan MA, Northwood JB, Levy F, Verhaegh SJ, Farrell DJ, Van Belkum A, Hays JP (2010) bro {beta}-lactamase and antibiotic resistances in a global cross-sectional study of Moraxella catarrhalis from children and adults. J Antimicrob Chemother 65(1):91–97

    CAS  Article  Google Scholar 

  30. Kaur R, Morris M, Pichichero ME (2017) Epidemiology of acute otitis media in the postpneumococcal conjugate vaccine era. Pediatrics 140(3):e20170181

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Sanofi Pasteur. We thank all the nurses and staff of pediatric practices, the parents who consented, the children who participated in this, study and the lab members (Karin Pryharski, Eduardo Gonzalez) who performed the microbiology over the years. Edna Yellamaty assisted with antibiotic susceptibility testing in the clinical microbiology lab of Rochester General Hospital.

Funding

Sanofi Pasteur funded this study but had no role in study design, data analysis, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, 1425 Portland Avenue, NY, 14621, Rochester, USA

    Ravinder Kaur, Naoko Fuji & Michael E. Pichichero

Authors
  1. Ravinder Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoko Fuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael E. Pichichero
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Kaur has collected and analyzed the data. She wrote the overall manuscript. Dr. Fuji helped in data analysis and manuscript writing. Dr. Pichichero designed the study along with manuscript writing.

Corresponding author

Correspondence to Michael E. Pichichero.

Ethics declarations

Ethics approval

The study was approved by the Rochester General Hospital Institutional Review Board, and the study was performed in accordance with the ethical standards as set out by such.

Consent to participate

Written informed consent was obtained from the parents.

Consent for publication

Parents signed informed consent regarding publishing their data.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 141 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kaur, R., Fuji, N. & Pichichero, M.E. Dynamic changes in otopathogens colonizing the nasopharynx and causing acute otitis media in children after 13-valent (PCV13) pneumococcal conjugate vaccination during 2015–2019. Eur J Clin Microbiol Infect Dis 41, 37–44 (2022). https://doi.org/10.1007/s10096-021-04324-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-021-04324-0

Keywords

  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Moraxella catarrhalis
  • Serotypes
  • Antibiotic susceptibility