1887

Abstract

Despite universal susceptibility to β-lactams, resistance to second-line antimicrobials (e.g. erythromycin) is increasingly common among group A (GAS). To better understand the frequency of regional GAS antimicrobial resistance, we screened a previously described GAS strain collection from Houston, TX, USA, for resistance to commonly used antimicrobials. A total of 100/929 (10.8 %) showed resistance to at least one antimicrobial. Tetracycline resistance was identified in 52 (5.6 %) GAS strains. The cumulative frequency of erythromycin and clindamycin resistance [macrolide (M) and macrolide-lincosamide-streptogramin (MLS) phenotypes] was greatest among invasive GAS strains (9.9 %) compared to that of strains derived from any other infection type (5.9 %, =0.045). We identified types 11, 75, 77 and 92 as the only types with high (e.g. >50 %) within- type resistance and contributing to the majority (24/26; 92 %) of erythromycin/clindamycin resistance in invasive GAS. High-frequency resistance types were also significantly overrepresented in invasive GAS strains as indicated by invasive index. We performed whole-genome sequencing to define genetic elements associated with resistance among types 11, 75, 77 and 92. Diverse mobile elements contributed to GAS resistance including transposons, integrative conjugative elements, prophage and a plasmid. Phylogenetic analysis suggests recent clonal emergence of GAS strains. Our findings indicate that less frequently encountered GAS types disproportionately contribute to resistance phenotypes, are defined by diverse mobile genetic elements and may favour invasive disease.

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2019-11-01
2024-05-12
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References

  1. Nelson GE, Pondo T, Toews K-A, Farley MM, Lindegren ML et al. Epidemiology of invasive group A streptococcal infections in the United States, 2005–2012. Clin Infect Dis 2016; 63:478–486 [View Article]
    [Google Scholar]
  2. Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics 2010; 126:e557–e564 [View Article]
    [Google Scholar]
  3. Pickering LK, Baker CJ, Kimberlin DW, Long SS. (editors) Red Book, 29th edn. Elk Grove Village, IL: American Academy of Pediatrics; 2012
    [Google Scholar]
  4. Gagliotti C, Nobilio L, Milandri M, Moro ML. for the Emilia-Romagna Antibiotic Resistance Study Group Macrolide prescriptions and erythromycin resistance of Streptococcus pyogenes . Clin Infect Dis 2006; 42:1153–1156 [View Article]
    [Google Scholar]
  5. Papenburg J, Fontela PS, Freitas RR, Burstein B. Inappropriate antibiotic prescribing for acute bronchiolitis in US emergency departments, 2007-2015. J Pediatric Infect Dis Soc 2019 [View Article]
    [Google Scholar]
  6. CDC Antibiotic Resistance Threats in the United States Atlanta, GA: CDC; 2013
    [Google Scholar]
  7. Roberts AP, Mullany P. Tn 916 -like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance. FEMS Microbiol Rev 2011; 35:856–871 [View Article]
    [Google Scholar]
  8. Beres SB, Musser JM. Contribution of exogenous genetic elements to the group A Streptococcus metagenome. PLoS One 2007; 2:e800 [View Article]
    [Google Scholar]
  9. Flores AR, McNeil JC, Shah B, Van Beneden C, Shelburne SA. Capsule-negative emm types are an increasing cause of pediatric group A streptococcal infections at a large pediatric hospital in Texas. J Pediatric Infect Dis Soc 2019; 8:244–250
    [Google Scholar]
  10. CLSI Performance Standards for Antimicrobial Disk Susceptibility Tests, 13th edn. Wayne, PA: Clinical and Laboratory Standards Institute; 2018
    [Google Scholar]
  11. Flores AR, Luna RA, Runge JK, Shelburne SA, Baker CJ. Cluster of fatal group A streptococcal emm87 infections in a single family: molecular basis for invasion and transmission. J Infect Dis 2017; 215:1648–1652 [View Article]
    [Google Scholar]
  12. Chochua S, Metcalf BJ, Li Z, Rivers J, Mathis S et al. Population and whole genome sequence based characterization of invasive group A streptococci recovered in the United States during 2015. MBio 2017; 8:e01422-17 [View Article]
    [Google Scholar]
  13. Chalker V, Jironkin A, Coelho J, Al-Shahib A, Platt S et al. Genome analysis following a national increase in scarlet fever in England 2014. BMC Genomics 2017; 18:224 [View Article]
    [Google Scholar]
  14. Palmieri C, Mingoia M, Massidda O, Giovanetti E, Varaldo PE. Streptococcus pneumoniae transposon Tn1545/Tn6003 changes to Tn6002 due to spontaneous excision in circular form of the erm(B)- and aphA3-containing macrolide-aminoglycoside-streptothricin (MAS) element. Antimicrob Agents Chemother 2012; 56:5994–5997 [View Article]
    [Google Scholar]
  15. Iannelli F, Santagati M, Santoro F, Oggioni MR, Stefani S et al. Nucleotide sequence of conjugative prophage Φ1207.3 (formerly Tn1207.3) carrying the mef(A)/msr(D) genes for efflux resistance to macrolides in Streptococcus pyogenes . Front Microbiol 2014; 5:687 [View Article]
    [Google Scholar]
  16. Malhotra-Kumar S, Mazzariol A, Van Heirstraeten L, Lammens C, de Rijk P et al. Unusual resistance patterns in macrolide-resistant Streptococcus pyogenes harbouring erm(A) . J Antimicrob Chemother 2009; 63:42–46 [View Article]
    [Google Scholar]
  17. Woodbury RL, Klammer KA, Xiong Y, Bailiff T, Glennen A et al. Plasmid-borne erm(T) from invasive, macrolide-resistant Streptococcus pyogenes strains. Antimicrob Agents Chemother 2008; 52:1140–1143 [View Article]
    [Google Scholar]
  18. Athey TBT, Teatero S, Sieswerda LE, Gubbay JB, Marchand-Austin A et al. High incidence of invasive group A Streptococcus disease caused by strains of uncommon emm types in Thunder Bay, Ontario, Canada. J Clin Microbiol 2016; 54:83–92 [View Article]
    [Google Scholar]
  19. Tanz RR, Shulman ST, Shortridge VD, Kabat W, Kabat K et al. Community-based surveillance in the United States of macrolide-resistant pediatric pharyngeal group A streptococci during 3 respiratory disease seasons. Clin Infect Dis 2004; 39:1794–1801 [View Article]
    [Google Scholar]
  20. Richter SS, Heilmann KP, Beekmann SE, Miller NJ, Miller AL et al. Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003. Clin Infect Dis 2005; 41:599–608 [View Article]
    [Google Scholar]
  21. Cameron DR, Howden BP, Peleg AY. The interface between antibiotic resistance and virulence in Staphylococcus aureus and its impact upon clinical outcomes. Clin Infect Dis 2011; 53:576–582 [View Article]
    [Google Scholar]
  22. Kaito C, Saito Y, Nagano G, Ikuo M, Omae Y et al. Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence. PLoS Pathog 2011; 7:e1001267 [View Article]
    [Google Scholar]
  23. Relf WA, Martin DR, Sriprakash KS. Identification of sequence types among the M-nontypeable group A streptococci. J Clin Microbiol 1992; 30:3190–3194
    [Google Scholar]
  24. Beall B, Facklam R, Hoenes T, Schwartz B. Survey of emm gene sequences and T-antigen types from systemic Streptococcus pyogenes infection isolates collected in San Francisco, California; Atlanta, Georgia; and Connecticut in 1994 and 1995. J Clin Microbiol 1997; 35:1231–1235
    [Google Scholar]
  25. Da Cunha V, Davies MR, Douarre P-E, Rosinski-Chupin I, Margarit I et al. Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline. Nat Commun 2014; 5:4544 [View Article]
    [Google Scholar]
  26. Flores AR, Galloway-Peña J, Sahasrabhojane P, Saldaña M, Yao H et al. Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes. Proc Natl Acad Sci USA 2015; 112:6431–6436 [View Article]
    [Google Scholar]
  27. Fittipaldi N, Beres SB, Olsen RJ, Kapur V, Shea PR et al. Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus . Am J Pathol 2012; 180:1522–1534 [View Article]
    [Google Scholar]
  28. Willems RJL, Hanage WP, Bessen DE, Feil EJ. Population biology of gram-positive pathogens: high-risk clones for dissemination of antibiotic resistance. FEMS Microbiol Rev 2011; 35:872–900 [View Article]
    [Google Scholar]
  29. Bessen DE, Sotir CM, Readdy TL, Hollingshead SK. Genetic correlates of throat and skin isolates of group A streptococci. J Infect Dis 1996; 173:896–900 [View Article]
    [Google Scholar]
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