Abstract
Staphylococcus aureus bloodstream infections (SABSI) are associated with a high burden of morbidity and mortality. The impact of specific S. aureus genotypes on outcome is unclear. The aim of this study was to evaluate the epidemiology and outcome of SABSI, with a special emphasis on the impact of bacterial clonal lineage on mortality. We conducted a 3-year population-based prospective study between 2011 and 2014, including 303 consecutive adult patients. Clinical data were obtained from interviews and medical records. S. aureus isolates were genotyped using DNA microarrays. The incidence rate of SABSI was 27.6 per 100,000 inhabitants [95 % confidence interval (CI) 24.6–31.0]. The median age of the patients was 71 years (interquartile range 56–81 years) and 61.4 % were male. Most SABSI (70.6 %) occurred in hospitals or associated to healthcare, and 34.1 % of these were associated with intravascular catheters. Only five (1.6 %) SABSI were caused by methicillin-resistant S. aureus (MRSA). The 30-day case fatality rate was 20.8 % (95 % CI 16.6–25.7). S. aureus clonal complex 30 [hazard ratio (HR) 3.9; 95 % CI 1.8–8.5, p = 0.001], unknown focus of infection (HR 4.5; 95 % CI 1.9–10.8, p = 0.001) and respiratory tract infection (HR 12.7; 95 % CI 4.6–34.6, p < 0.001) were independent predictors of mortality in a Cox regression analysis after adjusting for age, sex and underlying conditions. A high proportion of potential preventable SABSI calls for effective infection control measures. S. aureus clonal complex 30 genotype was associated with mortality in patients with bloodstream infections. The genetic basis underlying this association remains to be demonstrated.
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References
Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH, Reller LB, Cheng AC, Dudley T, Oddone EZ (2003) Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 163(17):2066–2072
Asgeirsson H, Gudlaugsson O, Kristinsson KG, Heiddal S, Kristjansson M (2011) Staphylococcus aureus bacteraemia in Iceland, 1995–2008: changing incidence and mortality. Clin Microbiol Infect 17(4):513–518
Lyytikäinen O, Ruotsalainen E, Järvinen A, Valtonen V, Ruutu P (2005) Trends and outcome of nosocomial and community-acquired bloodstream infections due to Staphylococcus aureus in Finland, 1995–2001. Eur J Clin Microbiol 24(6):399–404
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(2):362–386
Vogel M, Schmitz RP, Hagel S, Pletz MW, Gagelmann N, Scherag A, Schlattmann P, Brunkhorst FM (2016) Infectious disease consultation for Staphylococcus aureus bacteremia—A systematic review and meta-analysis. J Infect 72(1):19–28. doi:10.1016/j.jinf.2015.09.037
Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y (2003) Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36:53–59. doi:10.1086/345476
Kaasch AJ, Barlow G, Edgeworth JD, Fowler VG Jr, Hellmich M, Hopkins S, Kern WV, Llewelyn MJ, Rieg S, Rodriguez-Baño J, Scarborough M, Seifert H, Soriano A, Tilley R, Tőrők ME, Weiß V, Wilson AP, Thwaites GE; ISAC, INSTINCT, SABG, UKCIRG, and Colleagues (2014) Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect 68(3):242–251
Paul M, Kariv G, Goldberg E, Raskin M, Shaked H, Hazzan R, Samra Z, Paghis D, Bishara J, Leibovici L (2010) Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 65:2658–2665. doi:10.1093/jac/dkq373
Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ (2002) Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137:791–797
Benfield T, Espersen F, Frimodt-Møller N, Jensen AG, Larsen AR, Pallesen LV, Skov R, Westh H, Skinhøj P (2007) Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect 13:257–263. doi:10.1111/j.1469-0691.2006.01589.x
El Atrouni WI, Knoll BM, Lahr BD, Eckel-Passow JE, Sia IG, Baddour LM (2009) Temporal trends in the incidence of Staphylococcus aureus bacteremia in Olmsted County, Minnesota, 1998 to 2005: a population-based study. Clin Infect Dis 49(12):e130–e138
Huggan PJ, Wells JE, Browne M, Richardson A, Murdoch DR, Chambers ST (2010) Population-based epidemiology of Staphylococcus aureus bloodstream infection in Canterbury, New Zealand. Intern Med J 40(2):117–125
Laupland KB, Lyytikäinen O, Søgaard M, Kennedy KJ, Knudsen JD, Ostergaard C, Galbraith JC, Valiquette L, Jacobsson G, Collignon P, Schønheyder HC; International Bacteremia Surveillance Collaborative (2013) The changing epidemiology of Staphylococcus aureus bloodstream infection: a multinational population-based surveillance study. Clin Microbiol Infect 19(5):465–471
Mitchell BG, Gardner A, Stuart L (2012) The epidemiology of Staphylococcus aureus bacteraemia in Tasmania. Healthc Infect 17(3):98–103
Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298(15):1763–1771
Rieg S, Jonas D, Kaasch AJ, Porzelius C, Peyerl-Hoffmann G, Theilacker C, Küpper M-F, Schneider C, Seifert H, Kern WV (2013) Microarray-based genotyping and clinical outcomes of Staphylococcus aureus bloodstream infection: an exploratory study. PLoS One 8(8):e71259
Rasmussen G, Monecke S, Brus O, Ehricht R, Söderquist B (2014) Long term molecular epidemiology of methicillin-susceptible Staphylococcus aureus bacteremia isolates in Sweden. PLoS One 9(12):e114276
Grundmann H, Aanensen DM, van den Wijngaard CC, Spratt BG, Harmsen D, Friedrich AW; European Staphylococcal Reference Laboratory Working Group (2010) Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a molecular-epidemiological analysis. PLoS Med 7(1):e1000215. doi:10.1371/journal.pmed.1000215
Fowler VG Jr, Nelson CL, McIntyre LM, Kreiswirth BN, Monk A, Archer GL, Federspiel J, Naidich S, Remortel B, Rude T, Brown P, Reller LB, Corey GR, Gill SR (2007) Potential associations between hematogenous complications and bacterial genotype in Staphylococcus aureus infection. J Infect Dis 196(5):738–747
Nienaber JJC, Sharma Kuinkel BK, Clarke-Pearson M, Lamlertthon S, Park L, Rude TH, Barriere S, Woods CW, Chu VH, Marín M, Bukovski S, Garcia P, Corey GR, Korman T, Doco-Lecompte T, Murdoch DR, Reller LB, Fowler VG Jr; International Collaboration on Endocarditis-Microbiology Investigators (2011) Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins. J Infect Dis 204(5):704–713
Aamot HV, Blomfeldt A, Eskesen AN (2012) Genotyping of 353 Staphylococcus aureus bloodstream isolates collected between 2004 and 2009 at a Norwegian university hospital and potential associations with clinical parameters. J Clin Microbiol 50(9):3111–3114
Gottlieb GS, Fowler VG Jr, Kong LK, McClelland RS, Gopal AK, Marr KA, Li J, Sexton DJ, Glower D, Corey GR (2000) Staphylococcus aureus bacteremia in the surgical patient: a prospective analysis of 73 postoperative patients who developed Staphylococcus aureus bacteremia at a tertiary care facility. J Am Coll Surg 190(1):50–57
Lautenschlager S, Herzog C, Zimmerli W (1993) Course and outcome of bacteremia due to Staphylococcus aureus: evaluation of different clinical case definitions. Clin Infect Dis 16(4):567–573. doi:10.1093/clind/16.4.567
Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR (2000) Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 30(4):633–638. doi:10.1086/313753
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent J-L, Ramsay G; International Sepsis Definitions Conference (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29(4):530–538. doi:10.1007/s00134-003-1662-x
Monecke S, Slickers P, Ehricht R (2008) Assignment of Staphylococcus aureus isolates to clonal complexes based on microarray analysis and pattern recognition. FEMS Immunol Med Microbiol 53(2):237–251
Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, Borg M, Chow H, Ip M, Jatzwauk L, Jonas D, Kadlec K, Kearns A, Laurent F, O’Brien FG, Pearson J, Ruppelt A, Schwarz S, Scicluna E, Slickers P, Tan HL, Weber S, Ehricht R (2011) A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One 6(4):e17936. doi:10.1371/journal.pone.0017936
Tong SY, Chen LF, Fowler VG Jr (2012) Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance? Semin Immunopathol 34(2):185–200
Miko BA, Hafer CA, Lee CJ, Sullivan SB, Hackel MA, Johnson BM, Whittier S, Della-Latta P, Uhlemann A-C, Lowy FD (2013) Molecular characterization of methicillin-susceptible Staphylococcus aureus clinical isolates in the United States, 2004 to 2010. J Clin Microbiol 51(3):874–879
Chambers HF (2001) The changing epidemiology of Staphylococcus aureus? Emerg Infect Dis 7(2):178–182
Elstrøm P, Kacelnik O, Bruun T, Iversen B, Hauge SH, Aavitsland P (2012) Meticillin-resistant Staphylococcus aureus in Norway, a low-incidence country, 2006–2010. J Hosp Infect 80(1):36–40
Mylotte JM, Tayara A (2000) Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clin Infect Dis 31(5):1170–1174. doi:10.1086/317421
Wertheim HFL, van Leeuwen WB, Snijders S, Vos MC, Voss A, Vandenbroucke-Grauls CMJE, Kluytmans JAJW, Verbrugh HA, van Belkum AV (2005) Associations between Staphylococcus aureus genotype, infection, and in-hospital mortality: a nested case–control study. J Infect Dis 192(7):1196–1200
Xiong YQ, Fowler VG, Yeaman MR, Perdreau-Remington F, Kreiswirth BN, Bayer AS (2009) Phenotypic and genotypic characteristics of persistent methicillin-resistant Staphylococcus aureus bacteremia in vitro and in an experimental endocarditis model. J Infect Dis 199(2):201–208
Price J, Baker G, Heath I, Walker-Bone K, Cubbon M, Curtis S, Enright MC, Lindsay J, Paul J, Llewelyn M (2010) Clinical and microbiological determinants of outcome in Staphylococcus aureus bacteraemia. Int J Microbiol 2010:654858. doi:10.1155/2010/654858
Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G, O’Brien FG, Tenover FC, McDougal LK, Monk AB, Enright MC (2005) Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet 365(9466):1256–1258
Limbago BM, Kallen AJ, Zhu W, Eggers P, McDougal LK, Albrecht VS (2014) Report of the 13th vancomycin-resistant Staphylococcus aureus isolate from the United States. J Clin Microbiol 52(3):998–1002
Rieg S, Peyerl-Hoffmann G, de With K, Theilacker C, Wagner D, Hübner J, Dettenkofer M, Kaasch A, Seifert H, Schneider C, Kern WV (2009) Mortality of S. aureus bacteremia and infectious diseases specialist consultation—a study of 521 patients in Germany. J Infect 59(4):232–239
Paulsen J, Mehl A, Askim Å, Solligård E, Åsvold BO, Damås JK (2015) Epidemiology and outcome of Staphylococcus aureus bloodstream infection and sepsis in a Norwegian county 1996–2011: an observational study. BMC Infect Dis 15(1):116
Asgeirsson H, Kristjansson M, Kristinsson KG, Gudlaugsson O (2011) Staphylococcus aureus bacteraemia—nationwide assessment of treatment adequacy and outcome. J Infect 62(5):339–346
Dendle C, Martin RD, Cameron DR, Grabsch EA, Mayall BC, Grayson ML, Johnson PD (2009) Staphylococcus aureus bacteraemia as a quality indicator for hospital infection control. Med J Aust 191(7):389–392
Duerden B, Fry C, Johnson AP, Wilcox MH (2015) The control of methicillin-resistant Staphylococcus aureus blood stream infections in England. Open Forum Infect Dis 2(2):ofv035. doi:10.1093/ofid/ofv035
Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C (2006) An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 355(26):2725–2732
Mitchell BG, Collignon PJ, McCann R, Wilkinson IJ, Wells A (2014) A major reduction in hospital-onset Staphylococcus aureus bacteremia in Australia—12 years of progress: an observational study. Clin Infect Dis 59(7):969–975
Berenholtz SM, Pronovost PJ, Lipsett PA, Hobson D, Earsing K, Farley JE, Milanovich S, Garrett-Mayer E, Winters BD, Rubin HR, Dorman T, Perl TM (2004) Eliminating catheter-related bloodstream infections in the intensive care unit. Crit Care Med 32(10):2014–2020
Gasink LB, Lautenbach E (2008) Prevention and treatment of health care-acquired infections. Med Clin North Am 92(2):295–313
Richards C, Emori TG, Peavy G, Gaynes R (2001) Promoting quality through measurement of performance and response: prevention success stories. Emerg Infect Dis 7(2):299–301
Geubbels EL, Bakker HG, Houtman P, van Noort-Klaassen MA, Pelk MS, Sassen TM, Wille JC (2004) Promoting quality through surveillance of surgical site infections: five prevention success stories. Am J Infect Control 32(7):424–430
Collignon PJ, Wilkinson IJ, Gilbert GL, Grayson ML, Whitby RM (2006) Health care-associated Staphylococcus aureus bloodstream infections: a clinical quality indicator for all hospitals. Med J Aust 184(8):404–406
Chen P-Y, Chuang Y-C, Wang J-T, Chang S-C (2015) Impact of prior healthcare-associated exposure on clinical and molecular characterization of methicillin-susceptible Staphylococcus aureus bacteremia: results from a retrospective cohort study. Medicine (Baltimore) 94(5):e474
Cardoso T, Almeida M, Friedman ND, Aragão I, Costa-Pereira A, Sarmento AE, Azevedo L (2014) Classification of healthcare-associated infection: a systematic review 10 years after the first proposal. BMC Med 12(1):40
Acknowledgements
We thank Karin Helmersen and colleagues at Akershus University Hospital, Department of Microbiology and Infection Control, for the technical assistance and infectious diseases specialist Margrethe Astrup for evaluating the clinical data. We thank Antje Ruppelt at the Medical Faculty Carl Gustav Carus, Dresden, Germany, for the technical assistance with the microarrays and Stefan Monecke at Alere Technologies GmbH, Jena, Germany, for the interpretation of the microarray results.
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The study was supported by a Strategic Research grant (2619028/90003) from Akershus University Hospital.
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Ethical approval was given by the Norwegian Regional Ethics Committee South-East (2009/2149-1) and by the Data Protection Official at Akershus University Hospital (2010-041).
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Written informed consent was obtained from all individual participants included in the study, except for a small fraction of patients (n = 22) who died before an interview could be performed and consent could be asked for.
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Blomfeldt, A., Eskesen, A.N., Aamot, H.V. et al. Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality. Eur J Clin Microbiol Infect Dis 35, 803–813 (2016). https://doi.org/10.1007/s10096-016-2601-4
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DOI: https://doi.org/10.1007/s10096-016-2601-4