Skip to main content
SpringerLink
Log in

Interaction of the heptavalent pneumococcal conjugate vaccine and the use of individual antibiotics among children on nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The purpose of this study was to assess the complex interaction of the heptavalent pneumococcal conjugate vaccine (PCV7) and individual classes of antimicrobial agents on the nasopharyngeal carriage of erythromycin-resistant pneumococci within the day-care center population. Between February 2005 and May 2007, nasopharyngeal cultures for Streptococcus pneumoniae were obtained from 1,829 day-care center attendees in Central Greece. Thirty-one percent of the pneumococci were erythromycin-resistant; 85.2% of these isolates were also penicillin-nonsusceptible. PCV7 immunization was associated with decreased carriage of erythromycin-resistant PCV7 serotypes but not with an overall decrease in erythromycin-resistant S. pneumoniae colonization. The largest decline in the carriage of erythromycin-resistant pneumococci, particularly of PCV7 serotypes, was observed among vaccinated attendees who had not been exposed to antimicrobials within the preceding 3 months. Exposure to macrolides, 90% clarithromycin, significantly correlated with erythromycin resistance (adjusted odds ratio [AOR] = 2.08, 95% confidence interval [CI] = 1.38–3.12). There was a trend toward an association between the use of oral cephalosporins, other than cefprozil and cefaclor, and colonization with erythromycin-resistant pneumococci (AOR = 1.91, 95% CI = 0.92–3.96). Penicillins had a nonsignificant correlation with the carriage of erythromycin-resistant pneumococci (AOR = 1.17, 95% CI = 0.80–1.71). Despite the widespread PCV7 immunization, the antibiotic pressure, particularly of macrolides, continues to cause dissemination of erythromycin-resistant, commonly multidrug-resistant, pneumococci within the day-care center population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Klein JO (1981) The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis 3:246–253

    CAS  PubMed  Google Scholar 

  2. Gray BM, Converse GM 3rd, Dillon HC Jr (1980) Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 142:923–933

    CAS  PubMed  Google Scholar 

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

  4. Sleeman KL, Griffiths D, Shackley F, Diggle L, Gupta S, Maiden MC, Moxon ER, Crook DW, Peto TEA (2006) Capsular serotype-specific attack rates and duration of carriage of Streptococcus pneumoniae in a population of children. J Infect Dis 194:682–688. doi:10.1086/505710

    Article  PubMed  Google Scholar 

  5. Samore MH, Lipsitch M, Alder SC, Haddadin B, Stoddard G, Williamson J, Sebastian K, Carroll K, Ergonul O, Carmeli Y, Sande MA (2006) Mechanisms by which antibiotics promote dissemination of resistant pneumococci in human populations. Am J Epidemiol 163:160–170. doi:10.1093/aje/kwj021

    Article  PubMed  Google Scholar 

  6. Syrogiannopoulos GA, Grivea IN, Beratis NG, Spiliopoulou AE, Fasola EL, Bajaksouzian S, Appelbaum PC, Jacobs MR (1997) Resistance patterns of Streptococcus pneumoniae from carriers attending day-care centers in southwestern Greece. Clin Infect Dis 25:188–194

    Article  CAS  PubMed  Google Scholar 

  7. Syrogiannopoulos GA, Grivea IN, Davies TA, Katopodis GD, Appelbaum PC, Beratis NG (2000) Antimicrobial use and colonization with erythromycin-resistant Streptococcus pneumoniae in Greece during the first 2 years of life. Clin Infect Dis 31:887–893. doi:10.1086/318118

    Article  CAS  PubMed  Google Scholar 

  8. Dagan R, Givon-Lavi N, Zamir O, Fraser D (2003) Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J 22:532–540

    Article  PubMed  Google Scholar 

  9. Nunes S, Sá-Leão R, Carriço J, Alves CR, Mato R, Avô AB, Saldanha J, Almeida JS, Sanches IS, de Lencastre H (2005) Trends in drug resistance, serotypes, and molecular types of Streptococcus pneumoniae colonizing preschool-age children attending day care centers in Lisbon, Portugal: a summary of 4 years of annual surveillance. J Clin Microbiol 43:1285–1293. doi:10.1128/JCM.43.3.1285-1293.2005

    Article  CAS  PubMed  Google Scholar 

  10. Van Eldere J, Meekers E, Lagrou K, Massonet C, Canu A, Devenyns I, Verhaegen J, Syrogiannopoulos G, Leclercq R (2005) Macrolide-resistance mechanisms in Streptococcus pneumoniae isolates from Belgium. Clin Microbiol Infect 11:332–334. doi:10.1111/j.1469-0691.2005.01077.x

    Article  PubMed  Google Scholar 

  11. Jacobs MR, Good CE, Beall B, Bajaksouzian S, Windau AR, Whitney CG (2008) Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience. J Clin Microbiol 46:982–990. doi:10.1128/JCM.02321-07

    Article  PubMed  Google Scholar 

  12. Farrell DJ, Klugman KP, Pichichero M (2007) Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States. Pediatr Infect Dis J 26:123–128. doi:10.1097/01.inf.0000253059.84602.c3

    Article  PubMed  Google Scholar 

  13. Inoue M, Farrell DJ, Kaneko K, Akizawa K, Fujita S, Kaku M, Igari J, Yamaguchi K, Yamanaka K, Murase M, Asari S, Hirakata Y, Baba H, Itaha H (2008) Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1–5 (1999–2004). Microb Drug Resist 14:109–117. doi:10.1089/mdr.2008.0806

    Article  CAS  PubMed  Google Scholar 

  14. Yang F, Xu XG, Yang MJ, Zhang YY, Klugman KP, McGee L (2008) Antimicrobial susceptibility and molecular epidemiology of Streptococcus pneumoniae isolated from Shanghai, China. Int J Antimicrob Agents 32:386–391. doi:10.1016/j.ijantimicag.2008.05.004

    Article  PubMed  Google Scholar 

  15. Syrogiannopoulos GA, Katopodis GD, Grivea IN, Beratis NG (2002) Antimicrobial use and serotype distribution of nasopharyngeal Streptococcus pneumoniae isolates recovered from Greek children younger than 2 years old. Clin Infect Dis 35:1174–1182. doi:10.1086/343824

    Article  PubMed  Google Scholar 

  16. Huang SS, Platt R, Rifas-Shiman SL, Pelton SI, Goldmann D, Finkelstein JA (2005) Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics 116:e408–e413. doi:10.1542/peds.2004-2338

    Article  PubMed  Google Scholar 

  17. Hennessy TW, Singleton RJ, Bulkow LR, Bruden DL, Hurlburt DA, Parks D, Moore M, Parkinson AJ, Schuchat A, Butler JC (2005) Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity. Vaccine 23:5464–5473. doi:10.1016/j.vaccine.2005.08.100

    Article  CAS  PubMed  Google Scholar 

  18. Cohen R, Levy C, de La Rocque F, Gelbert N, Wollner A, Fritzell B, Bonnet E, Tetelboum R, Varon E (2006) Impact of pneumococcal conjugate vaccine and of reduction of antibiotic use on nasopharyngeal carriage of nonsusceptible pneumococci in children with acute otitis media. Pediatr Infect Dis J 25:1001–1007. doi:10.1097/01.inf.0000243163.85163.a8

    Article  PubMed  Google Scholar 

  19. Grivea IN, Panagiotou M, Tsantouli AG, Syrogiannopoulos GA (2008) Impact of heptavalent pneumococcal conjugate vaccine on nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae among day-care center attendees in central Greece. Pediatr Infect Dis J 27:519–525. doi:10.1097/INF.0b013e318168d28a

    Article  PubMed  Google Scholar 

  20. Hellenic National Committee for Immunizations. National Immunization Program (2006) Paediatriki 69:78–82

    Google Scholar 

  21. Clinical and Laboratory Standards Institute (CLSI) (2008) Performance standards for antimicrobial susceptibility testing. Eighteenth informational supplement M100-S18. CLSI, Wayne, Pennsylvania

    Google Scholar 

  22. Centers for Disease Control and Prevention (CDC) (2000) Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 49(RR-9):1–35

    Google Scholar 

  23. American Academy of Pediatrics (AAP) (2006) Pneumococcal infections. In: Pickering LK, Baker CJ, Long SS, McMillan JA (eds) Red book: 2006 report of the Committee on Infectious Diseases, 27th edn. AAP, Elk Grove Village, Illinois, pp 525–537

    Google Scholar 

  24. Lipsitch M (2001) Measuring and interpreting associations between antibiotic use and penicillin resistance in Streptococcus pneumoniae. Clin Infect Dis 32:1044–1054. doi:10.1086/319604

    Article  CAS  PubMed  Google Scholar 

  25. Finkelstein JA, Huang SS, Daniel J, Rifas-Shiman SL, Kleinman K, Goldmann D, Pelton SI, DeMaria A, Platt R (2003) Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample. Pediatrics 112:862–869

    Article  PubMed  Google Scholar 

  26. Dagan R, Leibovitz E, Greenberg D, Yagupsky P, Fliss DM, Leiberman A (1998) Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients. Pediatr Infect Dis J 17:880–885

    Article  CAS  PubMed  Google Scholar 

  27. Ghaffar F, Muniz LS, Katz K, Reynolds J, Smith JL, Davis P, Friedland IR, McCracken GH Jr (2000) Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media. Clin Infect Dis 31:875–880. doi:10.1086/318160

    Article  CAS  PubMed  Google Scholar 

  28. Greenberg D, Givon-Lavi N, Sharf AZ, Vardy D, Dagan R (2008) The association between antibiotic use in the community and nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae in Bedouin children. Pediatr Infect Dis J 27:776–782

    Article  PubMed  Google Scholar 

  29. Toltzis P, Dul M, O’Riordan MA, Toltzis H, Blumer JL (2005) Impact of amoxicillin on pneumococcal colonization compared with other therapies for acute otitis media. Pediatr Infect Dis J 24:24–28

    Article  PubMed  Google Scholar 

  30. Jacobs MR, Bajaksouzian S, Windau A, Good CE, Lin G, Pankuch GA, Appelbaum PC (2004) Susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to 17 oral antimicrobial agents based on pharmacodynamic parameters: 1998–2001 U.S. Surveillance Study. Clin Lab Med 24:503–530. doi:10.1016/j.cll.2004.03.008

    Article  PubMed  Google Scholar 

  31. Varon E, Levy C, de La Rocque F, Boucherat M, Deforche D, Podglajen I, Navel M, Cohen R (2000) Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections. Clin Infect Dis 31:477–481. doi:10.1086/313981

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This paper was presented in part at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America 46th Annual Meeting, Washington, DC, October 2008 (abstract no. G1-2104).

We thank Dr. Elias Zintzaras for performing the statistical analysis. The study was partially supported by an investigator-initiated grant from Wyeth Vaccines and the 3089 grant from the Research Committee of the University of Thessaly, Greece.

G.A.S.: received grant support from Wyeth. I.N.G., A.G.T., and D.C.C.: no potential conflicts.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Thessaly, School of Medicine, General University Hospital, Biopolis, 411 10, Larissa, Greece

    Ioanna N. Grivea, Alexandra G. Tsantouli, Denise C. Chryssanthopoulou & George A. Syrogiannopoulos

Authors
  1. Ioanna N. Grivea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra G. Tsantouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denise C. Chryssanthopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George A. Syrogiannopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George A. Syrogiannopoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grivea, I.N., Tsantouli, A.G., Chryssanthopoulou, D.C. et al. Interaction of the heptavalent pneumococcal conjugate vaccine and the use of individual antibiotics among children on nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae . Eur J Clin Microbiol Infect Dis 29, 97–105 (2010). https://doi.org/10.1007/s10096-009-0826-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-009-0826-1

Keywords

Search

Navigation