1887

Abstract

infections cause significant morbidity and mortality in children and adolescents.

There is limited data on the characteristics of infections requiring hospitalization in childhood.

To investigate the molecular epidemiology and antibiotic resistance of clinical isolates from children and adolescents.

All isolates recovered from patients aged <18 years, admitted to a referral hospital, with culture-proven invasive or non-invasive infections during the 4 year period 2015 to 2018 were analysed for antimicrobial resistance, virulence genes, PFGE and multilocus sequence typing (MLST). Cases were assigned to community-associated, community-onset healthcare-associated or hospital-associated infections based on epidemiological case definitions.

Among 139  infections, 88.5 % (123/139) were caused by methicillin-susceptible isolates (MSSA) and 73.4 % (102/139) were classified as community-associated infections. and genes were more common among MRSA as compared to MSSA isolates ( p 0.04; p 0.007). Invasive disease was noted in 22/139 patients (15.8 %). Staphylococcal scalded skin syndrome caused by fusidic-resistant MSSA increased over time (22.8 % in 2017–2018 vs 8.3 % in 2015–2016, OR 3.24; 95 % CI 1.10–8.36; 0.03). By PFGE genotyping, 22 pulsotypes were identified. A total of five sequence types (STs) were identified among 58 isolates analysed by MLST. More than one third of MSSA isolates (40/123, 32.5 %) and 13/23 (56.5 %) of SSSS isolates belonged to pulsotype 1, classified as sequence type 121 (ST121). MRSA isolates were equally distributed to pulsotypes A (ST30), B (ST239), C (ST80), H (ST225). ST121 isolates carried (40/40), genes (29/40), exhibited high resistance to fusidic acid and were increasingly resistant to mupirocin.

In our population, community-associated MSSA was the predominant cause of infections characterized by polyclonality, increasing resistance to fusidic acid and mupirocin. PFGE type 1 ST121 clone, harboured exfoliative toxin genes and was associated with rising trends of SSSS.

Keyword(s): MRSA , PVL , SSSS , ST121 , Staphylococcus aureus and virulence
Funding
This study was supported by the:
  • European Society for Paediatric Infectious Disease (Award ESPID Small Grant 2017)
    • Principle Award Recipient: MARIATSIRIGOTAKI
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2022-03-31
2022-05-18
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References

  1. Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015; 28:603–661 [View Article] [PubMed]
    [Google Scholar]
  2. Hultén KG, Mason EO, Lamberth LB, Forbes AR, Revell PA et al. Analysis of invasive community-acquired methicillin-susceptible Staphylococcus aureus infections during a period of declining community acquired methicillin-resistant Staphylococcus aureus infections at a large children’s hospital. Pediatr Infect Dis J 2018; 37:235–241 [View Article] [PubMed]
    [Google Scholar]
  3. Crandall H, Kapusta A, Killpack J, Heyrend C, Nilsson K et al. Clinical and molecular epidemiology of invasive Staphylococcus aureus infection in Utah children; continued dominance of MSSA over MRSA. PLoS One 2020; 15:e0238991 [View Article] [PubMed]
    [Google Scholar]
  4. Gopal Rao G, Batura R, Nicholl R, Coogan F, Patel B et al. Outbreak report of investigation and control of an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in neonates and mothers. BMC Infect Dis 2019; 19:178 [View Article] [PubMed]
    [Google Scholar]
  5. Ismail H, Govender NP, Singh-Moodley A, van Schalkwyk E, Shuping L et al. An outbreak of cutaneous abscesses caused by Panton-Valentine leukocidin-producing methicillin-susceptible Staphylococcus aureus among gold mine workers, South Africa, November 2017 to March 2018. BMC Infect Dis 2020; 20:621 [View Article] [PubMed]
    [Google Scholar]
  6. Bartlett AH, Hulten KG. Staphylococcus aureus pathogenesis: secretion systems, adhesins, and invasins. Pediatr Infect Dis J 2010; 29:860–861 [View Article] [PubMed]
    [Google Scholar]
  7. Ladhani S. Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus . FEMS Immunol Med Microbiol 2003; 39:181–189 [View Article] [PubMed]
    [Google Scholar]
  8. Bukowski M, Wladyka B, Dubin G. Exfoliative toxins of Staphylococcus aureus . Toxins (Basel) 2010; 2:1148–1165 [View Article] [PubMed]
    [Google Scholar]
  9. Handler MZ, Schwartz RA. Staphylococcal scalded skin syndrome: diagnosis and management in children and adults. J Eur Acad Dermatol Venereol 2014; 28:1418–1423 [View Article] [PubMed]
    [Google Scholar]
  10. Otto M. Basis of virulence in community-associated methicillin-resistant Staphylococcus aureus . Annu Rev Microbiol 2010; 64:143–162 [View Article] [PubMed]
    [Google Scholar]
  11. Josse J, Laurent F, Diot A. Staphylococcal adhesion and host cell invasion: fibronectin-binding and other mechanisms. Front Microbiol 2017; 8:2433 [View Article] [PubMed]
    [Google Scholar]
  12. Shinji H, Yosizawa Y, Tajima A, Iwase T, Sugimoto S et al. Role of fibronectin-binding proteins A and B in in vitro cellular infections and in vivo septic infections by Staphylococcus aureus . Infect Immun 2011; 79:2215–2223 [View Article] [PubMed]
    [Google Scholar]
  13. Otto M. Staphylococcus aureus toxins. Curr Opin Microbiol 2014; 17:32–37 [View Article] [PubMed]
    [Google Scholar]
  14. Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem 2004; 68:981–1003 [View Article] [PubMed]
    [Google Scholar]
  15. Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 2003; 9:978–984 [View Article] [PubMed]
    [Google Scholar]
  16. Sdougkos G, Chini V, Papanastasiou DA, Christodoulou G, Stamatakis E et al. Community-associated Staphylococcus aureus infections and nasal carriage among children: molecular microbial data and clinical characteristics. Clin Microbiol Infect 2008; 14:995–1001 [View Article] [PubMed]
    [Google Scholar]
  17. Moschou A, Maraki S, Giormezis N, Moraitaki H, Stafylaki D et al. Prevalence and molecular epidemiology of Staphylococcus aureus nasal colonization in four nursing home residents in Crete, Greece. J Infect Chemother 2020; 26:199–204 [View Article] [PubMed]
    [Google Scholar]
  18. Maree CL, Daum RS, Boyle-Vavra S, Matayoshi K, Miller LG. Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections. Emerg Infect Dis 2007; 13:236–242 [View Article] [PubMed]
    [Google Scholar]
  19. Clinical and Laboratory Standards Institute Performance standards for antimicrobial susceptibility testing: 28th informational supplement.Wayne, PA: Clinical and Laboratory Standards Institute. M100-S28 2018
    [Google Scholar]
  20. Boye K, Schønning K, Westh H, Lisby G. Fast screening for MRSA by quadriplex real- time PCR Barcelona Spain, Poster Number: 1534: 2014
    [Google Scholar]
  21. Stegger M, Andersen PS, Kearns A, Pichon B, Holmes MA et al. Rapid detection, differentiation and typing of methicillin-resistant Staphylococcus aureus harbouring either mecA or the new mecA homologue mecA(LGA251). Clin Microbiol Infect 2012; 18:395–400 [View Article] [PubMed]
    [Google Scholar]
  22. Jarraud S, Mougel C, Thioulouse J, Lina G, Meugnier H et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 2002; 70:631–641 [View Article] [PubMed]
    [Google Scholar]
  23. Gomes AR, Vinga S, Zavolan M, de Lencastre H. Analysis of the genetic variability of virulence-related loci in epidemic clones of methicillin-resistant Staphylococcus aureus . Antimicrob Agents Chemother 2005; 49:366–379 [View Article] [PubMed]
    [Google Scholar]
  24. Miragaia M, Carriço JA, Thomas JC, Couto I, Enright MC et al. Comparison of molecular typing methods for characterization of Staphylococcus epidermidis: proposal for clone definition. J Clin Microbiol 2008; 46:118–129 [View Article] [PubMed]
    [Google Scholar]
  25. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995; 33:2233–2239 [View Article] [PubMed]
    [Google Scholar]
  26. Thomas JC, Vargas MR, Miragaia M, Peacock SJ, Archer GL et al. Improved multilocus sequence typing scheme for Staphylococcus epidermidis . J Clin Microbiol 2007; 45:616–619 [View Article] [PubMed]
    [Google Scholar]
  27. European Centre for Disease Prevention and Control (ECDC) Antimicrobial Resistance Surveillance in Europe 2012. Annual Report of the European Antimicrobial Resistance Surveillance Network Stockholm: ECDC; 2013
    [Google Scholar]
  28. Niniou I, Vourli S, Lebessi E, Foustoukou M, Vatopoulos A et al. Clinical and molecular epidemiology of community-acquired, methicillin-resistant Staphylococcus aureus infections in children in central Greece. Eur J Clin Microbiol Infect Dis 2008; 27:831–837 [View Article] [PubMed]
    [Google Scholar]
  29. Katopodis GD, Grivea IN, Tsantsaridou AJ, Pournaras S, Petinaki E et al. Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece. BMC Infect Dis 2010; 10:351 [View Article] [PubMed]
    [Google Scholar]
  30. Drougka E, Foka A, Liakopoulos A, Doudoulakakis A, Jelastopulu E et al. A 12-year survey of methicillin-resistant Staphylococcus aureus infections in Greece: ST80-IV epidemic?. Clin Microbiol Infect 2014; 20:796–803 [View Article] [PubMed]
    [Google Scholar]
  31. Doudoulakakis AG, Bouras D, Drougka E, Kazantzi M, Michos A et al. Community-associated Staphylococcus aureus pneumonia among Greek children: epidemiology, molecular characteristics, treatment, and outcome. Eur J Clin Microbiol Infect Dis 2016; 35:1177–1185 [View Article] [PubMed]
    [Google Scholar]
  32. Hultén KG, Mason EO, Lamberth LB, Forbes AR, Revell PA et al. Analysis of invasive community-acquired methicillin-susceptible Staphylococcus aureus infections during a period of declining community acquired methicillin-resistant Staphylococcus aureus infections at a large children’s hospital. Pediatr Infect Dis J 2018; 37:235–241 [View Article] [PubMed]
    [Google Scholar]
  33. Mairi A, Touati A, Lavigne J-P. Methicillin-resistant Staphylococcus aureus ST80 clone: a systematic review. Toxins (Basel) 2020; 12:E119 [View Article] [PubMed]
    [Google Scholar]
  34. Doudoulakakis A, Spiliopoulou I, Syridou G, Giormezis N, Militsopoulou M et al. Emergence of staphylococcal scalded skin syndrome associated with a new toxinogenic, methicillin-susceptible Staphylococcus aureus clone. J Med Microbiol 2019; 68:48–51 [View Article] [PubMed]
    [Google Scholar]
  35. Hultén KG, Kok M, King KE, Lamberth LB, Kaplan SL. Increasing Numbers of Staphylococcal Scalded Skin Syndrome Cases Caused by ST121 in Houston, Texas. Pediatr Infect Dis J 2020; 39:30–34 [View Article] [PubMed]
    [Google Scholar]
  36. Schefold JC, Esposito F, Storm C, Heuck D, Krüger A et al. Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report. J Med Case Rep 2007; 1:1752–1947 [View Article] [PubMed]
    [Google Scholar]
  37. Rao Q, Shang W, Hu X, Rao X. Staphylococcus aureus ST121: a globally disseminated hypervirulent clone. J Med Microbiol 2015; 64:1462–1473 [View Article] [PubMed]
    [Google Scholar]
  38. Conceição T, Aires-de-Sousa M, Pona N, Brito MJ, Barradas C et al. High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children. Eur J Clin Microbiol Infect Dis 2011; 30:293–297 [View Article] [PubMed]
    [Google Scholar]
  39. Azarian T, Cella E, Baines SL, Shumaker MJ, Samel C et al. Genomic epidemiology and global population structure of exfoliative toxin A-producing Staphylococcus aureus strains associated with staphylococcal scalded skin syndrome. Front Microbiol 2021; 12:663831 [View Article] [PubMed]
    [Google Scholar]
  40. Doudoulakakis A, Spiliopoulou I, Spyridis N, Giormezis N, Kopsidas J et al. Emergence of a Staphylococcus aureus clone resistant to mupirocin and fusidic acid carrying exotoxin genes and causing mainly skin infections. J Clin Microbiol 2017; 55:2529–2537 [View Article] [PubMed]
    [Google Scholar]
  41. Togashi A, Aung MS, Yoto Y, Tsugawa T, Sueoka H et al. Septic arthritis caused by an emerging ST121 methicillin-susceptible, PVL-negative Staphylococcus aureus harbouring a variant of bone sialoprotein-binding protein gene. New Microbes New Infect 2017; 19:17–18 [View Article] [PubMed]
    [Google Scholar]
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