Skip to main content

Advertisement

Log in

Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007–2019

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

Abstract

The aim of this study is to present the first nationwide microbiological and epidemiological study of invasive group A Streptococcus (iGAS) disease in Spain. One thousand eight hundred ninety-three iGAS isolates were analyzed over 2007–2019. emm typing was performed by sequencing the gene’s variable 5’ end, exotoxin genes were identified by PCR, and antimicrobial susceptibility explored via the E test and disk diffusion. Five hundred twenty-three isolates were associated with sepsis, 292 with cellulitis, 232 with scarlet fever, 153 with pneumonia, 141 with streptococcal toxic shock syndrome, and 94 with necrotizing fasciitis. The most prevalent emm types were emm1 (449/1893 isolates), emm89 (210/1893), emm3 (208/1893), emm4 (150/1893), emm12 (112/1893) emm6 (107/1893), emm87 (89/1893), emm28 (88/1893), emm75 (78/1893), emm77 (78/1893), emm11 (58/1893), and emm22 (35/1893). emm1, emm3, emm4, and emm6 were the predominant types affecting children (mostly respiratory infections), while emm11, emm77, and emm89 prevailed in the elderly (mostly skin infections). Each emm type was associated with one or more exotoxin gene (spe, sme, and ssa) profiles. speA was detected in 660 isolates, speB in 1829, speC in 1014, speF in 1826, speG in 1651, speJ in 716, speH in 331, smeZ in 720, and ssa in 512. Isolates with speA were associated with the most severe infections. Penicillin susceptibility was universal. Two hundred twenty-four isolates were resistant to tetracycline, 169 to erythromycin, and 81 to clindamycin. Tetracycline, erythromycin, and clindamycin resistance rates declined over the study period. The above information could serve as the basis for continued surveillance efforts designed to control disease cause by this bacterium.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bisno AL, Brito MO, Collins CM (2003) Molecular basis of group A streptococcal virulence. Lancet Infect Dis 3:191–200. https://doi.org/10.1016/S1473-3099(03)00576-0

    Article  CAS  PubMed  Google Scholar 

  2. Cole JN, Barnett T, Nizet V, Walker MJ (2011) Molecular insight into invasive group A streptococcal disease. Nat Rev 9:724–736. https://doi.org/10.1038/nrmicro2648

    Article  CAS  Google Scholar 

  3. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, Sriprakash KS, Sanderson-Smith ML, Nizet V (2014) Disease manifestations and pathogenic mechanisms of group A Streptococcus. Clin Microbiol Rev 27:264–301. https://doi.org/10.1128/CMR.00101-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fischetti VA (1989) Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev 2:285–314. https://doi.org/10.1128/cmr.2.3.285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Smeesters PR, McMillan DJ, Sriprakash KS (2010) The streptococcal M protein: a highly versatile molecule. Trends Microbiol 18:275–282. https://doi.org/10.1016/j.tim.2010.02.007

    Article  CAS  PubMed  Google Scholar 

  6. Bessen DE, McShan WM, Nguyen SV, Shetty A, Agrawal S, Tettelin H (2015) Molecular epidemiology and genomics of group A streptococcus. Infect Genet Evol 33:393–418. https://doi.org/10.1016/j.meegid.2014.10.011

    Article  CAS  PubMed  Google Scholar 

  7. Working Group on Severe Streptococcal Infections (1993) Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. JAMA 269:390–391

    Article  Google Scholar 

  8. Efstratiou A (2000) Group A streptococci in the 1990s. J Antimicrob Chemother 45:3–12. https://doi.org/10.1093/jac/45.suppl_1.3

    Article  CAS  PubMed  Google Scholar 

  9. Carapetis JR, Steer AC, Mulholland EK, Weber M (2005) The global burden of group A streptococcal diseases. Lancet Infect Dis 5:685–694. https://doi.org/10.1016/S1473-3099(05)70267-X

    Article  PubMed  Google Scholar 

  10. Hamilton SM, Stevens DL, Bryant AE (2013) Pregnancy-related group A streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome. Clin Infect Dis 57:870–876. https://doi.org/10.1093/cid/cit282

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sumby P, Porcella SF, Madrigal AG, Barbian KD, Virtaneva K, Ricklefs SM, Sturdevant DE, Graham MR, Vuopio-Varkila J, Hoe NP (2005) Musser JM (2005) Evolutionary origin and emergence of a highly successful clone of serotype M1 group A Streptococcus involved multiple horizontal gene transfer events. J Infect Dis 192:771–782. https://doi.org/10.1086/432514

    Article  CAS  PubMed  Google Scholar 

  12. Barnett TC, Bowen AC, Carapetis JR (2019) The fall and rise of group A Streptococcus diseases. Epidemiol Infect 147:e4,1–e4,6. https://doi.org/10.1017/S0950268818002285

    Article  Google Scholar 

  13. Turner CE, Abbott J, Lamagni T, Holden MTG, David S, Jones MD, Game L, Efstratiou A, Sriskandan S (2015) Emergence of a new highly successful acapsular group A Streptococcus clade of genotype emm89 in the United Kingdom. mBio 6:e00622–e00615. https://doi.org/10.1128/mBio.00622-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lamagni TL, Darenberg J, Luca-Harari B, Siljander T, Efstratiou A, Henriques-Normark B, Vuopio-Varkila J, Bouvet A, Creti R, Ekelund K, Koliou M, Reinert RR, Stathi A, Strakova L, Ungureanu V, Schalén C, Strep-EURO Study Group, Jasir A (2008) Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 46:2359–2367. https://doi.org/10.1128/JCM.00422-08

    Article  PubMed  PubMed Central  Google Scholar 

  15. Luca-Harari B, Darenberg J, Neal S, Siljander T, Strakova L, Tanna A, Creti R, Ekelund K, Koliou M, Tassios PT, van der Linden M, Straut M, Vuopio-Varkila J, Bouvet A, Efstratiou A, Schalén C, Henriques-Normark B, Strep-EURO Study Group, Jasir A (2009) Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 47:1155–1165. https://doi.org/10.1128/JCM.02155-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Creti R, Imperi M, Baldassarri L, Pataracchia M, Recchia S, Alfarone G, Orefici G (2007) emm types, virulence factors, and antibiotic resistance of invasive Streptococcus pyogenes isolates from Italy: what has changed in 11 years? J Clin Microbiol 45:2249–2256. https://doi.org/10.1128/JCM.00513-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Darenberg J, Henriques-Normark B, Lepp T, Teggmark-Wissell K, Tegnell A, Widgren K (2013) Increased incidence of invasive group A streptococcal infections in Sweden, January 2012-February 2013. Eur Surveill 18(14):20443. https://doi.org/10.2807/1560-7917.es2013.18.14.20443

    Article  CAS  Google Scholar 

  18. Lepoutre A, Doloy A, Bidet P, Leblond A, Perrocheau A, Bingen E, Trieu-Cuot P, Bouvet A, Poyart C, Lévy-Bruhl D, Microbiologists of the Epibac Network (2011) Epidemiology of invasive Streptococcus pyogenes infections in France in 2007. J Clin Microbiol 49:4094–4100. https://doi.org/10.1128/JCM.00070-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Luca-Harari B, Ekelund K, van der Linden M, Staum-Kaltoft M, Hammerum AM, Jasir A (2008) Clinical and epidemiological aspects of invasive Streptococcus pyogenes in Denmark during 2003 and 2004. J Clin Microbiol 46:79–86. https://doi.org/10.1128/jcm.01626-07

    Article  CAS  PubMed  Google Scholar 

  20. Naseer U, Steinbakk M, Blystad H, Caugant DA (2016) Epidemiology of invasive group A streptococcal infections in Norway 2010-2014: a retrospective cohort study. Eur J Clin Microbiol Infect Dis 35:1639–1648. https://doi.org/10.1007/s10096-016-2704-y

    Article  CAS  PubMed  Google Scholar 

  21. Nelson GE, Pondo T, Toews KA, Farley MM, Lindegren ML, Lynfield R, Aragon D, Zansky SM, Watt JP, Cieslak PR, Angeles K, Harrison LH, Petit S, Beall B, van Veneden CA (2016) Epidemiology of invasive group A streptococcal infections in the United States, 2005-2012. Clin Infect Dis 63:478–486. https://doi.org/10.1093/cid/ciw248

    Article  PubMed  Google Scholar 

  22. Olafsdottir LB, Erlensdóttir H, Melo-Cristino J, Weinberger DM, Ramírez M, Kristinsson KG, Gottfredsson M (2014) Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012. Euro Surveill 19(17):20784. https://doi.org/10.2807/1560-7917.ES2014.19.17.20784

    Article  PubMed  Google Scholar 

  23. Vlaminckx BJM, van Pelt W, Schouls LM, van Silfhout A, Mascini EM, Elzenaar CP, Fernandes T, Bosman A, Schellekens JFP (2005) Long-term surveillance of invasive group A streptococcal disease in The Netherlands, 1994-2003. Clin Microbiol Infect 11:226–231. https://doi.org/10.1111/j.1469-0691.2004.01068.x

    Article  CAS  PubMed  Google Scholar 

  24. Instituto de Salud Carlos III. Centro Nacional de Microbiología. Área de Orientación Diagnóstica. Programas de Vigilancia de Bacterias. Vigilancia de la Infección Estreptocócica https://www.isciii.es/QueHacemos/Servicios/DiagnosticoMicrobiol%C3%B3gicoyProgramasVigilancia/Paginas/default.aspx. Accessed 16 March 2021.

  25. Center for Disease Control and Prevention. Streptococcus Laboratory. Available at: https://www.cdc.gov/streplab/groupa-strep/index.html. Accessed 16 March 2021

  26. Schmitz FJ, Beyer A, Charpentier E, Henriques Normark B, Schade M, Fluit AC, Hafner D, Novak R (2003) Toxin-gene profile heterogeneity among endemic invasive European group A streptococcal isolates. J Infect Dis 188:1578–1586. https://doi.org/10.1086/379230

    Article  CAS  PubMed  Google Scholar 

  27. The European Committee of Antimicrobial Susceptibility Testing. Clinical breakpoints–bacteria(v10.0).https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10.0_Breakpoint_Tables.pdf. Accessed 16 March 2021.

  28. Giovanetti E, Montanari MP, Mingoia M, Varaldo PE (1999) Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains in Italy and heterogeneity of inducibly resistant strains. Antimicrob Agents Chemother 43:1935–1940. https://doi.org/10.1128/AAC.43.8.1935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Montes M, Ardanuy C, Tamayo E, Domènech A, Liñares J, Pérez-Trallero E (2011) Epidemiological and molecular analysis of Streptococcus pyogenes causing invasive disease in Spain (1998-2009): comparison with non-invasive isolates. Eur J Clin Microbiol Infect Dis 30:1295–1302. https://doi.org/10.1007/s10096-011-1226-x

    Article  CAS  PubMed  Google Scholar 

  30. Tamayo E, Montes M, García-Arenzana JM, Pérez-Trallero E (2014) Streptococcus pyogenes emm-types in northern Spain; population dynamics over a 7-year period. J Inf Secur 68:50–57. https://doi.org/10.1016/j.jinf.2013.08.013

    Article  Google Scholar 

  31. Sánchez-Encinales V, Ludwig G, Tamayo E, García-Arenzana JM, Muñoz-Almagro C, Montes M (2019) Molecular characterization of Streptococcus pyogenes causing invasive disease in pediatric population in Spain, a 12-year study. Pediatr Infect Dis J 38:1168–1172. https://doi.org/10.1097/INF.0000000000002471

    Article  PubMed  Google Scholar 

  32. Instituto Nacional de Estadítica de España. Available at: http://www.ine.es. Accessed 16 March 2021

  33. Steer AC, Law I, Matatolu L, Beall BW, Carapetis JR (2009) Global emm type distribution of group a streptococci: systematic review and implications for vaccine development. Lancet Infect 9:611–616. https://doi.org/10.1016/S1473-3099(09)70178-1

    Article  Google Scholar 

  34. Commons R, Rogers S, Gooding T, Danchin M, Carapetis J, Robins-Browne R, Curtis N (2008) Superantigen genes in group A streptococcal isolates and their relationship with emm types. J Med Microbiol 57:1238–1246. https://doi.org/10.1099/jmm.0.2008/001156-0

    Article  CAS  PubMed  Google Scholar 

  35. Lintges M, van der Linden M, Hilgers RD, Arlt S, Al-Lahham A, Reinert RR, Plücken S, Rink L (2010) Superantigen genes are more important than the emm type for the invasiveness of group A Streptococcus infection. J Infect Dis 202:20–28. https://doi.org/10.1086/653082

    Article  PubMed  Google Scholar 

  36. Dale JB, Penfound TA, Chiang EY, Walton WJ (2011) New 30-valent M protein-based vaccine evokes cross-opsonic antibodies against non-vaccine serotypes of group A streptococci. Vaccine 29:8175–8178. https://doi.org/10.1016/j.vaccine.2011.09.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sanderson-Smith M, De Oliveira DMP, Guglielmini J, McMillan DJ, Vu T, Holien JK, Henningham A, Steer AC, Bessen DE, Dale JB, Curtis N, Beall BW, Walker MJ, Parker MW, Carapetis JR, van Melderen L, Sriprakash KS, Smeesters PR (2014) A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis 210:1325–1338. https://doi.org/10.1093/infdis/jiu260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ardanuy C, Domenech A, Rolo D, Calatayud L, Tubau F, Ayats J, Martín R, Liñares J (2010) Molecular characterization of macrolide- and multidrug-resistant Streptococcus pyogenes isolated from adult patients in Barcelona, Spain (1993-2008). J Antimicrob Chemother 65:634–643. https://doi.org/10.1093/jac/dkq006

    Article  CAS  PubMed  Google Scholar 

  39. Rubio-López V, Valdezate S, Álvarez D, Villalón P, Medina MJ, Salcedo C, Sáez-Nieto JA (2012) Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (1994-2006). BMC Microbiol 12:215. https://doi.org/10.1186/1471-2180-12-215

    Article  PubMed  PubMed Central  Google Scholar 

  40. Varaldo PE, Montanari MP, Giovanetti E (2009) Genetic elements responsible for erythromycin resistance in streptococci. Antimicrob Agents Chemother 53:343–353. https://doi.org/10.1128/AAC.00781-08

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the microbiology laboratories across Spain for their interest and participation in SPIGAS. We also thank Adrian Burton for editing and language assistance (Physical Evidence Scientific Translations; http://physicalevidence.es).

Funding

This work was partially funded by the Instituto de Salud Carlos III (MPY 377/18).

Author information

Authors and Affiliations

Authors

Contributions

Villalón P: conception and design of the study, acquisition, analysis and interpretation of data, and drafting the article. Sáez-Nieto JA, Rubio-López V, Medina-Pascual MJ, Garrido N, Carrasco G, and Pino-Rosa S: acquisition, analysis and interpretation of data, and critical review. Valdezate S: conception of the study, analysis and interpretation of data, critical review of the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Pilar Villalón.

Ethics declarations

Conflicts 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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villalón, P., Sáez-Nieto, J.A., Rubio-López, V. et al. Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007–2019. Eur J Clin Microbiol Infect Dis 40, 2295–2303 (2021). https://doi.org/10.1007/s10096-021-04279-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-021-04279-2

Keywords

Navigation