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  • 1 Medical University of Sofia, Bulgaria
  • 2 Medical University of Sofia, Bulgaria
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Serogroup 6 remains common in the pneumococcal-conjugated vaccine era in Bulgaria; therefore, we investigated its clonal and serotype dynamics. The antibiotic susceptibilities were assessed by broth microdilution. Strains identified as serogroup 6 with latex agglutination method were subjected to serotype-specific PCRs. Erythromycin-resistant strains were analyzed by PCR for presence of ermB and mefE genes. MLST was performed to define clonal composition of the sequence types (STs). Serogroup 6 was represented by 40 (13.3%) from 301 invasive and non-invasive Streptococcus pneumoniae isolates. Molecular serotyping revealed new emerging serotype 6C (6.6%), not detected in pre-vaccine era. Among unvaccinated patients, mostly we observed serotypes 6А (57.1%) and 6В (28.6%). Serotype 6C was distinctive for vaccinated children (64%), followed by 6A (24%). Penicillin and ceftriaxone non-susceptible serogroup 6 strains were 65% and 5%, respectively; erythromycin- and clindamycin-resistant were 70.0% and 52.5%, respectively. Multidrug-resistant strains were 57.5%. Prevalent genetic determinant for macrolide resistance was ermB gene (75%). MLST revealed 17 STs into 5 clonal complexes and 7 singletons. Predominant genetic lineage was CC386, represented by MDR-6C non-invasive strains. Serotype 6B, principally responsible for invasive diseases in the pre-vaccine era, retreated this position to serotype 6A.

  • 1.

    Pilishvili, T., Lexau, C., Farley, M. M., Hadler, J., Harrison, L. H., Bennett, N. M., Reingold, A., Thomas, A., Schaffner, W., Craig, A. S., Smith, P. J., Beall, B. W., Whitney, C. G., Moore, M. R.: Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 201, 3241 (2010).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Miller, E., Andrews, N. J., Waight, P. A., Slack, M. P., George, R. C.: Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: An observational cohort study. Lancet Infect Dis 11, 760768 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Parra, E. L., Duarte, C., Rodríguez, K., Sanabria, O., Moreno, J.: Frequency and molecular characterization of invasive isolates of Streptococcus pneumoniae serotypes 6C and 6D in Colombia. Enferm Infecc Microbiol Clin 35, 283286 (2017).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Baek, J. Y., Park, I. H., Song, J. H., Ko, K. S.: Prevalence of isolates of Streptococcus pneumoniae putative serotype 6E in South Korea. J Clin Microbiol 52, 20962099 (2014).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Jacobs, M. R., Bajaksouzian, S., Bonomo, R. A., Good, C. E., Windau, A. R., Hujer, A. M., Massire, C., Melton, R., Blyn, L. B., Ecker, D. J., Sampath, R.: Occurrence, distribution, and origins of Streptococcus pneumoniae serotype 6C, a recently recognized serotype. J Clin Microbiol 47, 6472 (2009).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Porat, N., Benisty, R., Givon-Lavi, N., Trefler, R., Dagan, R.: The impact of pneumococcal conjugate vaccines on carriage of and disease caused by Streptococcus pneumoniae serotypes 6C and 6D in southern Israel. Vaccine 27, 28062812 (2016).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Varghese, R., Jayaraman, R., Veeraraghavan, B.: Current challenges in the accurate identification of Streptococcus pneumoniae and its serogroups/serotypes in the vaccine era. J Microbiol Methods 141, 4854 (2017).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Millar, E. V., Watt, J. P., Bronsdon, M. A., Dallas, J., Reid, R., Santosham, M., O’Brien, K. L.: Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal colonization among unvaccinated household members. Clin Infect Dis 47, 989996 (2008).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Yun, K. W., Cho, E. Y., Choi, E. H., Lee, H. J.: Capsular polysaccharide gene diversity of pneumococcal serotypes 6A, 6B, 6C, and 6D. Int J Med Microbiol 304, 110917 (2014).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Pai, R., Limor, J., Beall, B.: Use of pyrosequencing to differentiate Streptococcus pneumoniae serotypes 6A and 6B. J Clin Microbiol 43, 48204822 (2005).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    The European Committee on Antimicrobial Susceptibility Testing: Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 6.0 (2018). Available at http://www.eucast.org.

    • Search Google Scholar
    • Export Citation
  • 12.

    Sutcliffe, J., Grebe, T., Tait-Kamradt, A., Wondrack, L.: Detection of erythromycin-resistant determinants by PCR. Antimicrob Agents Chemother 40, 25622566 (1996).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Jin, P., Xiao, M., Kong, F., Oftadeh, S., Zhou, F., Liu, C., Gilbert, G. L.: Simple, accurate, serotype-specific PCR assay to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C. J Clin Microbiol 47, 24702474 (2009).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Park, I. H., Park, S., Hollingshead, S. K., Nahm, M. H.: Genetic basis for the new pneumococcal serotype, 6C. Infect Immunol 75, 44824489 (2007).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Setchanova, L. P., Alexandrova, A., Dacheva, D., Mitov, I., Kaneva, R., Mitev, V.: Dominance of multidrug-resistant Denmark(14)-32 (ST230) clone among Streptococcus pneumoniae serotype 19A isolates causing pneumococcal disease in Bulgaria from 1992 to 2013. Microb Drug Resist 21, 3542 (2015).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Setchanova, L., Alexandrova, A., Mitov, I., Nashev, D., Kantardjiev, T.: The group for microbiological surveillance of pneumococci: Serotype distribution and antimicrobial resistance of invasive streptococcus pneumoniae isolates in Bulgaria before the introduction of pneumococcal conjugate vaccine. J Chemother 24, 1217 (2012).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Setchanova, L. P., Kostyanev, T., Alexandrova, A., Mitov, I., Nashev, D., Kantardjiev, T.: Microbiological characterization of Streptococcus pneumoniae and non-typeable Haemophilus influenzae isolates as primary causes of acute otitis media in Bulgarian children before the introduction of conjugate vaccines. Ann Clin Microbiol Antimicrob 12, 6 (2013).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Setchanova, L., Murdjeva, M., Stancheva, I., Alexandrova, A., Sredkova, M., Stoeva, T., Yoneva, M., Kurchatova, A., Mitov, I.: Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria. Braz J Infect Dis 21, 433440 (2017).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Rolo, D., Fenoll, A., Ardanuy, C., Calatayud, L., Cubero, M., de la Campa, A. G., Liñares, J.: Trends of invasive serotype 6C pneumococci in Spain: Emergence of a new lineage. J Antimicrob Chemother 66, 17121718 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Song, J. H., Baek, J. Y., Ko, K. S.: Comparison of capsular genes of Streptococcus pneumoniae serotype 6A, 6B, 6C, and 6D isolates. J Clin Microbiol 49, 17581764 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Elberse, K., Witteveen, S., van der Heide, H., van de Pol, I., Schot, C., van der Ende, A., Berbers, G., Schouls, L.: Sequence diversity within the capsular genes of Streptococcus pneumoniae serogroup 6 and 19. PLoS One 6, 25018 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Neves, F. P. G., Cardoso, N. T., Souza, A. R. V., Snyder, R. E., Marlow, M. M., Pinto, T. C. A., Teixeira, L. M., Riley, L. W.: Population structure of Streptococcus pneumoniae colonizing children before and after universal use of pneumococcal conjugate vaccines in Brazil: Emergence and expansion of the MDR serotype 6C-CC386 lineage. J Antimicrob Chemother 73, 2061212 (2018).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Janoir, C., Cohen, R., Levy, C., Bingen, E., Lepoutre, A., Gutmann, L., Varon, E., Observatoires Régionaux du Pneumocoque (ORP) network: Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France. PLoS One 9, e90935 (2014).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Diamantino-Miranda, J., Aguiar, S. I., Carriço, J. A., Melo-Cristino, J., Ramirez, M.: Clonal and serotype dynamics of serogroup 6 isolates causing invasive pneumococcal disease in Portugal: 1999–2012. PLoS One 12, e0170354 (2017).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Marimon, J. M., Ercibengoa, M., Alonso, M., García-Medina, G., Pérez-Trallero, E.: Prevalence and molecular characterization of Streptococcus pneumoniae serotype 6C causing invasive disease in Gipuzkoa, northern Spain 1990–2009. Eur J Clin Microbiol Infect Dis 29, 10351038 (2010).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Andam, C. P., Mitchell, P. K., Callendrello, A., Chang, Q., Corander, J., Chaguza, C., McGee, L., Beall, B. W., Hanage, W. P.: Genomic epidemiology of penicillin – Nonsusceptible pneumococci with nonvaccine serotypes causing invasive disease in the United States. J Clin Microbiol 55, 11041115 (2017).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Carvalho Mda, G., Pimenta, F. C., Gertz, R. E., Jr, Joshi, H. H., Trujillo, A. A., Keys, L. E., Findley, J., Moura, I. S., Park, I. H., Hollingshead, S. K., Pilishvili, T., Whitney, C. G., Nahm, M. H., Beall, B. W., Active Bacterial Core Surveillance Team: PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype 6C, in the United States in 1999 and 2006 to 2007. J ClinMicrobiol 47, 554559 (2009).

    • Search Google Scholar
    • Export Citation
  • 28.

    Obolski, U., Lourenço, J., Thompson, C., Thompson, R., Gori, A., Gupta, S.: Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae. Proc Natl Acad Sci U S A 115, 31023107 (2018).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Hackel, M., Lascols, C., Bouchillon, S., Hilton, B., Morgenstern, D., Purdy, J.: Serotype prevalence and antibiotic resistance in Streptococcus pneumoniae clinical isolates among global populations. Vaccine 31, 48814887 (2013).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Bratcher, P. E., Park, I. H., Oliver, M. B., Hortal, M., Camilli, R., Hollingshead, S. K., Camou, T., Nahm, M. H.: Evolution of the capsular gene locus of Streptococcus pneumoniae serogroup 6. Microbiology 157, 189198 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Calatayud, L., Ardanuy, C., Tubau, F., Rolo, D., Grau, I., Pallarés, R., Martín, R., Liñares, J.: Serotype and genotype replacement among macrolide-resistant invasive pneumococci in adults: Mechanisms of resistance and association with different transposons. J Clin Microbiol 48, 13101316 (2010).

    • Crossref
    • Search Google Scholar
    • Export Citation

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