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  • 1 Medical Faculty University of Belgrade, Serbia
  • | 2 Institute for Pulmonary Diseases of Vojvodina, Serbia
  • | 3 University of Banja Luka, Bosnia and Herzegovina
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Numerous reports have confirmed that increased macrolide use in the treatment of respiratory tract infection has contributed to the emergence of antibiotic resistance worldwide. Studies have also shown that pneumococcal vaccine can reduce pneumococcal resistance. The aim of this study was to determine the prevalence of co-resistance to penicillin and other antibiotics in macrolide-resistant (MR) non-invasive pneumococcal isolates and to evaluate serotype distribution in resistant strains in the pre-vaccine era in Serbia. About 80% of MR isolates expressed the MLS phenotype with very high resistance to both erythromycin and clindamycin. A total of 132 (84.1%) MR isolates were multiresistant, i.e., they were resistant to erythromycin, penicillin, tetracycline, and trimethoprim–sulfamethoxazole. Among 157 MR pneumococci, 11 different serotypes were found. Four serotypes, 19F, 14, 6B, and 23F, accounted for 77.7% of all MR pneumococcal isolates. Among isolates with the cMLS phenotype, serotypes 19F and 14 were predominant, whereas serotype 6A was the most common among those with the M phenotype, followed by 14. In conclusion, co-resistance to macrolides and penicillin in our non-invasive pneumococcal isolates is high. The majority of tested strains (∼80%) belonged to the four serotypes (19F, 14, 6B, and 23F) that are included in all conjugate vaccine formulations.

  • 1.

    Advisory Committee on Immunization Practices: Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 49, 135 (2000).

    • Search Google Scholar
    • Export Citation
  • 2.

    Robinson, K. A., Baughman, W., Rothrock, G., Barrett, N. L., Pass, M., Lexau, C., Damaske, B., Stefonek, K., Barnes, B., Patterson, J., Zell, E. R., Schuchat, A., Whitney, C. G., Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network: Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: Opportunities for prevention in the conjugate vaccine era. JAMA 285, 17291735 (2001).

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

    Farha, T., Thomson, A. H.: The burden of pneumonia in children in the developed world. Paediatr Respir Rev 6, 7682 (2005).

  • 4.

    Felmingham, D., White, A. R., Jacobs, M. R., Appelbaum, P. C., Poupard, J., Miller, L. A., Grüneberg, R. N.: The Alexander Project: The benefits from a decade of surveillance. J Antimicrob Chemother 56, ii3ii21 (2005).

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

    European Centre for Disease Prevention and Control (ECDC): Antimicrobial resistance surveillance in Europe: Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control (ECDC), Luxembourg, 2014. Available at https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/antimicrobial-resistance-europe-2015.pdf

    • Search Google Scholar
    • Export Citation
  • 6.

    Leclercq, R., Courvalin, P.: Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. Antimicrob Agents Chemother 46, 27273274 (2002).

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

    Ambrose, K. D., Nisbet, R., Stephens, D. S.: Macrolide efflux in Streptococcus pneumoniae is mediated by a dual efflux pump (mel and mef) and is erythromycin inducible. Antimicrob Agents Chemother 49, 42034209 (2005).

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

    Bley, C., van der Linden, M., Reinert, R. R.: mef(A) is the predominant macrolide resistance determinant in Streptococcus pneumoniae and Streptococcus pyogenes in Germany. Int J Antimicrob Agents 37, 425431 (2011).

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

    Del Grosso, M., Camilli, R., Iannelli, F., Pozzi, G., Pantosti, A.: The mef(E)-carrying genetic element (mega) of Streptococcus pneumoniae: Insertion sites and association with other genetic elements. Antimicrob Agents Chemother 50, 33613366 (2006).

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

    Varaldo, P. E., Montanari, M. P., Giovanetti, E.: Genetic elements responsible for erythromycin resistance in streptococci. Antimicrob Agents Chemother 53, 343353 (2009).

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

    Gajic, I., Mijac, V., Ranin, L., Andjelkovic, D., Radicevic, M., Opavski, N.: Invasive isolates of Streptococcus pneumoniae in Serbia: Antimicrobial susceptibility and serotypes. Srp Arh Celok Lek 141, 4853 (2013).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Cillóniz, C., Amaro, R., Torres, A.: Pneumococcal vaccination. Curr Opin Infect Dis 29, 187196 (2016).

  • 13.

    The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 5.0, 2015. Available at http://www.eucast.org/ast_of_bacteria/previous_versions_of_documents/

    • Search Google Scholar
    • Export Citation
  • 14.

    Montanari, M. P., Mingoia, M., Giovanetti, E., Varaldo, P. E.: Differentiation of resistance phenotypes among erythromycin-resistant pneumococci. J Clin Microbiol 39, 13111315 (2001).

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

    Sirekbasan, L., Gönüllü, N., Sirekbasan, S., Kuşkucu, M., Midilli, K.: Phenotypes and genotypes of macrolide-resistant Streptococcus pneumoniae. Balkan Med J 32, 8488 (2015).

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

    European Medicines Agency. Summary of product characteristics, 2014. Available at http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000973/human_med_001071.jsp&mid=WC0b01ac058001d124. (last updated on January 9, 2018).

    • Search Google Scholar
    • Export Citation
  • 17.

    Felmingham, D., Canton, R., Jenkins, S. G.: Regional trends in beta-lactam, macrolide, fluoroquinolone and telithromycin resistance among Streptococcus pneumoniae isolates 2001–2004. J Infect 55, 111118 (2007).

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

    Reinert, R. R., Reinert, S., van der Linden, M., Cil, M. Y., Al-Lahham, A., Appelbaum, P.: Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother 49, 29032913 (2005).

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

    Cantón, R., Unal, S., Farrell, D. J.: Antibacterial resistance patterns in Streptococcus pneumoniae isolated from elderly patients: PROTEKT years 1–5 (1999–2004). Int J Antimicrob Agents 30, 546550 (2007).

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

    Inoue, M., Kaneko, K., Akizawa, K., Fujita, S., Kaku, M., Igari, J., Yamaguchi, K., Kohno, S., Yamanaka, K., Iinuma, Y., Murase, M., Yokoyama, T., Asari, S., Hirakata, Y.: Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1–3 (1999–2002). J Infect Chemother 12, 921 (2006).

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

    Mason, E. O. Jr., Wald, E. R., Bradley, J. S., Barson, W. J., Kaplan, S. L.: Macrolide resistance among middle ear isolates of Streptococcus pneumoniae observed at eight United States pediatric centers: Prevalence of M and MLSB phenotypes. Pediatr Infect Dis J 22, 623627 (2003).

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

    Wierzbowski, A. K., Nichol, K., Laing, N., Hisanaga, T., Nikulin, A., Karlowsky, J. A., Hoban, D. J., Zhanel, G. G.: Macrolide resistance mechanisms among Streptococcus pneumoniae isolated over 6 years of Canadian Respiratory Organism Susceptibility Study (CROSS) (1998–2004). J Antimicrob Chemother 60, 733740 (2007).

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

    Souli, M., Volonakis, K., Kapaskelis, A., Galani, I., Grammelis, V., Vorou, R., Tsivra, M., Chryssouli, Z., Katsala, D., Giamarellou, H.: Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003. Clin Microbiol Infect 13, 7077 (2007).

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

    Mijac, V., Opavski, N., Markovic, M., Gajic, I., Vasiljevic, Z., Sipetic, T., Bajcetic, M.: Trends in macrolide resistance of respiratory tract pathogens in the paediatric population in Serbia from 2004 to 2009. Epidemiol Infect 143, 648652 (2015).

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

    Versporten, A., Bolokhovets, G., Ghazaryan, L., Abilova, V., Pyshnik, G., Spasojevic, T., Korinteli, I., Raka, L., Kambaralieva, B., Cizmovic, L., Carp, A., Radonjic, V., Maqsudova, N., Celik, H. D., Payerl-Pal, M., Pedersen, H. B., Sautenkova, N., Goossens, H., WHO/Europe-ESAC Project Group: Antibiotic use in Eastern Europe: A cross-national database study in coordination with the WHO Regional Office for Europe. Lancet Infect Dis 14, 381387 (2014).

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

    Vestrheim, D. F., Hoiby, E. A., Aaberge, I. S., Caugant, D. A.: Impact of a pneumococcal conjugate vaccination program on carriage among children in Norway. Clin Vaccine Immunol 17, 325334 (2010).

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

    Bogaert, D., Sluijter, M., Toom, N. L., Mitchell, T. J., Goessens, W. H., Clarke, S. C., de Groot, R., Hermans, P. W.: Dynamics of pneumococcal colonization in healthy Dutch children. Microbiology 152, 377385 (2006).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Zemlickova, H., Urbaskova, P., Adamkova, V., Motlova, J., Lebedova, V., Prochazka, B.: Characteristics of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus isolated from the nasopharynx of healthy children attending day-care centres in the Czech Republic. Epidemiol Infect 134, 11791187 (2006).

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

    Tamm, E., Naaber, P., Maimets, M., Oona, M., Koljalg, S., Lutsar, I.: Antimicrobial susceptibility and serogroup/serotype distribution of nasopharyngeal isolates of Streptococcus pneumoniae in healthy Estonian children in 1999–2003. Clin Microbiol Infect 13, 824826 (2007).

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

    Poulakou, G., Katsarolis, I., Matthaiopoulou, I., Tsiodras, S., Kanavaki, S., Hatzaki, D., Roilides, E., Sofianou, D., Kavaliotis, I., Kansouzidou, A., Kafetzis, D. A., Paraskakis, I., Foustoukou, M., Daikos, G. L., Syriopoulou, V., Pangalis, A., Leveidiotou, S., Giamarellou, H., Hellenic Study Group for the Susceptibility of Streptococcus pneumoniae: Nationwide surveillance of Streptococcus pneumoniae in Greece: Patterns of resistance and serotype epidemiology. Int J Antimicrob Agents 30, 8792 (2007).

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

    Korona-Glowniak, I., Niedzielski, A., Malm, A.: Upper respiratory colonization by Streptococcus pneumoniae in healthy pre-school children in south-east Poland. Int J Pediatr Otorhinolaryngol 75, 15291534 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Falup-Pecurariu, O., Bleotu, L., Zavarache, C., Peled, N., Anton, O., Robu, M., Falup-Pecurariu, C., Rogozea, L., Porat, N., Greenberg, D., Dagan, R., Leibovitz, E.: Streptococcus pneumoniae nasopharyngeal colonization in children in Brasov, Central Romania: High antibiotic resistance and coverage by conjugate vaccines. Pediatr Infect Dis J 30, 7678 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Angoulvant, F., Cohen, R., Doit, C., Elbez, A., Werner, A., Béchet, S., Bonacorsi, S., Varon, E., Levy, C.: Trends in antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharyngeal flora in children with acute otitis media in France before and after 13 valent pneumococcal conjugate vaccine introduction. BMC Infect Dis 15, 236 (2015).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Daana, M., Rahav, G., Hamdan, A., Thalji, A., Jaar, F., Abdeen, Z., Jaber, H., Goral, A., Huppert, A., Raz, M., Regev-Yochay, G., PICR Study Group: Measuring the effects of pneumococcal conjugate vaccine (PCV7) on Streptococcus pneumoniae carriage and antibiotic resistance: The Palestinian-Israeli Collaborative Research (PICR). Vaccine 33, 10211026 (2015).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Sheppard, C., Fry, N.K., Mushtaq, S., Woodford, N., Reynolds, R., Janes, R., Pike, R., Hill, R., Kimuli, M., Staves, P., Doumith, M., Harrison, T., Livermore, D. M.: Rise of multidrug-resistant non-vaccine serotype 15A Streptococcus pneumoniae in the United Kingdom, 2001 to 2014. Euro Surveill 21, 30423 (2016).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Park, M., Kim, H. S., Kim, H. S., Park, J. Y., Song, W., Cho, H. C., Kim, J. S.: Novel levofloxacin-resistant multidrug-resistant Streptococcus pneumoniae serotype 11A isolates, South Korea. Emerg Infect Dis 22, 19781980 (2016).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    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
  • 38.

    Brenciani, A., Bacciaglia, A., Vecchi, M., Vitali, L. A., Varaldo, P. E., Giovanetti, E.: Genetic elements carrying erm(B) in Streptococcus pyogenes and association with tet(M) tetracycline resistance gene. Antimicrob Agents Chemother 51, 12091216 (2007).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Richter, S. S., Heilmann, K. P., Dohrn, C. L., Riahi, F., Diekema, D. J., Doern, G. V.: Pneumococcal serotypes before and after introduction of conjugate vaccines, United States, 1999–2011. Emerg Infect Dis 19, 10741083 (2013).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Weinberger, D. M., Malley, R., Lipsitch, M.: Serotype replacement in disease after pneumococcal vaccination. Lancet 378, 19621973 (2011).

    • Crossref
    • Search Google Scholar
    • Export Citation
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