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Fatality of Staphylococcus aureus infections in a Greek university hospital: role of inappropriate empiric treatment, methicillin resistance, and toxin genes’ presence

  • Ioanna Katsarou
  • Nefeli-Marina Paraskevopoulou
  • Matthaios Papadimitriou-Olivgeris
  • Nikolaos Giormezis
  • Maria Militsopoulou
  • Fevronia Kolonitsiou
  • Markos Marangos
  • Evangelos D. Anastassiou
  • Iris SpiliopoulouEmail author
Original Article

Abstract

The aim of the present study was to identify predictors of fatality among patients with S. aureus infections requiring hospitalization. Cases hospitalized with S. aureus infections at the University General Hospital of Patras, Greece, during a 4-year period (2013–2016) were studied. mecA, lukS/lukF-PV (Panton-Valentine leukocidin, PVL), tst (toxic shock syndrome toxin), fnbA (fibronectin-binding protein A), eta, and etb (epidermolytic toxins) genes’ carriage was detected by PCR in 149 selected patients. Among 464 patients, 346 were included (118 with missing data). Primary bacteremia predominated (44.2%), followed by lower respiratory tract infections (13.6%), deep seated infections (9.8%), osteoarticular (9.5%), and catheter-related bloodstream infections (6.1%). Methicillin-resistant S. aureus (MRSA) represented 33.8% of infections and were less likely to receive appropriate empiric treatment (79.5% versus 97.4%; P < 0.001). Thirty-day fatality was 14.5%. Multivariate analysis revealed that development of septic shock, Charlson Comorbidity Index, lower respiratory tract infection, bacteremia (primary or secondary), MRSA, and CRP was significantly associated with fatality. Appropriate empiric treatment was a predictor of good prognosis. Thirty-two out of 149 S. aureus (21.5%) carried lukS/lukF-PV genes, whereas, 14 (9.4%), 133 (78.7%), four (2.7%), and one (0.7%) carried tst, fnbA, eta, and etb genes, respectively. No difference was found among toxin genes’ presence and mortality. PVL was significantly more frequently found among MRSA as compared to MSSA (45.1% versus 9.2%; P < 0.001). MRSA represented one third of the infections requiring hospitalization and were independently associated with fatality, probably since were more likely to receive inappropriate antibiotic treatment as compared to MSSA.

Keywords

Staphylococcus aureus MRSA Bacteremia Pneumonia PVL Toxic shock syndrome toxin (TSST-1) Fatality 

Notes

Funding information

This work received no specific grant from any funding agency and was supported by internal funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Ethics Committee of the University General Hospital of Patras and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    European Centre for Disease Prevention and Control (ECDC) (2013) Point prevalence survey of healthcare associated infections and antimicrobial use in European acute care hospitals. ECDC, StockholmGoogle Scholar
  2. 2.
    Kolonitsiou F, Papadimitriou-Olivgeris M, Spiliopoulou A, Stamouli V, Papakostas V, Apostolopoulou E et al (2017) Trends of bloodstream infections in a University Greek Hospital during a three-year period: incidence of multidrug-resistant bacteria and seasonality in gram-negative predominance. Pol J Microbiol 66:171–180CrossRefGoogle Scholar
  3. 3.
    Bouchiat C, Curtis S, Spiliopoulou I, Bes M, Cocuzza C, Codita I et al (2017) MRSA infections among patients in the emergency department: a European multicentre study. J Antimicrob Chemother 72:372–375CrossRefGoogle Scholar
  4. 4.
    Drougka E, Foka A, Liakopoulos A, Doudoulakakis A, Jelastopulu E, Chini V et al (2014) A 12-year survey of methicillin-resistant Staphylococcus aureus infections in Greece: ST80-IV epidemic? Clin Microbiol Infect 20:O796–O803CrossRefGoogle Scholar
  5. 5.
    Argudin MA, Argumosa V, Mendoza MC, Guerra B, Rodicio MR (2013) Population structure and exotoxin gene content of methicillin-susceptible Staphylococcus aureus from Spanish healthy carriers. Microb Pathog 54:26–33CrossRefGoogle Scholar
  6. 6.
    Papadimitriou-Olivgeris M, Drougka E, Fligou F, Dodou V, Kolonitsiou F, Filos KS et al (2017) Spread of tst-positive Staphylococcus aureus strains belonging to ST30 clone among patients and healthcare workers in two intensive care units. Toxins (Basel) 9:E270CrossRefGoogle Scholar
  7. 7.
    Krakauer T (2019) Staphylococcal superantigens: pyrogenic toxins induce toxic shock. Toxins (Basel) 11Google Scholar
  8. 8.
    Josse J, Laurent F, Diot A (2017) Staphylococcal adhesion and host cell invasion: fibronectin-binding and other mechanisms. Front Microbiol 8:2433CrossRefGoogle Scholar
  9. 9.
    Paul M, Kariv G, Goldberg E, Raskin M, Shaked H, Hazzan R et al (2010) Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 65:2658–2665CrossRefGoogle Scholar
  10. 10.
    Soriano A, Martinez JA, Mensa J, Marco F, Almela M, Moreno-Martínez A et al (2000) Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia. Clin Infect Dis 30:368–373CrossRefGoogle Scholar
  11. 11.
    van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB (2012) Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev 25:362–386CrossRefGoogle Scholar
  12. 12.
    Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332CrossRefGoogle Scholar
  13. 13.
    Zhang K, Sparling J, Chow BL, Elsayed S, Hussain Z, Church DL et al (2004) New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol 42:4947–4955CrossRefGoogle Scholar
  14. 14.
    The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2017) Breakpoint tables for interpretation of MICs and zone diameters. Version 7.1. http://www.eucast.org
  15. 15.
    Morrison MA, Hageman JC, Klevens RM (2006) Case definition for community-associated methicillin-resistant Staphylococcus aureus. J Hosp Infect 62:241CrossRefGoogle Scholar
  16. 16.
    Jarraud S, Mougel C, Thioulouse J, Lina G, Meugnier H, Forey F et al (2002) Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 70:631–641CrossRefGoogle Scholar
  17. 17.
    Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K et al (2002) Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Infect Immun 70:4987–4996CrossRefGoogle Scholar
  18. 18.
    Papadimitriou-Olivgeris M, Kolonitsiou F, Zerva L, Lebessi E, Koutsia C, Drougka E et al (2015) Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008-2012). Diagn Microbiol Infect Dis 83:386–388CrossRefGoogle Scholar
  19. 19.
    Soriano A, Marco F, Martinez JA, Pisos E, Almela M, Dimova VP et al (2008) Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 46:193–200CrossRefGoogle Scholar
  20. 20.
    Wang SZ, Hu JT, Zhang C, Zhou W, Chen XF, Jiang LY et al (2014) The safety and efficacy of daptomycin versus other antibiotics for skin and soft-tissue infections: a meta-analysis of randomised controlled trials. BMJ Open 4:e004744CrossRefGoogle Scholar
  21. 21.
    Jiang H, Tang RN, Wang J (2013) Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: meta-analysis of randomised controlled trials. Eur J Clin Microbiol Infect Dis 32:1121–1128CrossRefGoogle Scholar
  22. 22.
    Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM et al (2008) Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother 52:3315–3320CrossRefGoogle Scholar
  23. 23.
    Shallcross LJ, Fragaszy E, Johnson AM, Hayward AC (2013) The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis. Lancet Infect Dis 13:43–54CrossRefGoogle Scholar
  24. 24.
    Zhang C, Guo L, Chu X, Shen L, Guo Y, Dong H et al (2016) Presence of the Panton-Valentine leukocidin genes in methicillin-resistant Staphylococcus aureus is associated with severity and clinical outcome of hospital-acquired pneumonia in a single center study in China. PLoS One 11:e0156704CrossRefGoogle Scholar
  25. 25.
    Wang M, Zheng Y, Mediavilla JR, Chen L, Kreiswirth BN, Song Y et al (2017) Hospital dissemination of tst-1-positive clonal complex 5 (CC5) methicillin-resistant Staphylococcus aureus. Front Cell Infect Microbiol 7:101PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ioanna Katsarou
    • 1
  • Nefeli-Marina Paraskevopoulou
    • 1
  • Matthaios Papadimitriou-Olivgeris
    • 2
    • 3
  • Nikolaos Giormezis
    • 4
  • Maria Militsopoulou
    • 1
  • Fevronia Kolonitsiou
    • 1
  • Markos Marangos
    • 2
  • Evangelos D. Anastassiou
    • 1
  • Iris Spiliopoulou
    • 1
    • 4
    Email author
  1. 1.Department of Microbiology, School of MedicineUniversity of PatrasPatrasGreece
  2. 2.Division of Infectious Diseases, School of MedicineUniversity of PatrasPatrasGreece
  3. 3.Department of Infectious DiseasesUniversity Hospital of LausanneLausanneSwitzerland
  4. 4.National Reference Laboratory for Staphylococci, School of MedicineUniversity of PatrasPatrasGreece

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