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Methicillin-resistant Staphylococcus aureus

Nature Reviews Disease Primers volume 4, Article number: 18033 (2018) Cite this article

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Abstract

Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most β-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.

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Figure 1: Worldwide prevalence of MRSA.
Figure 2: Prevalence of MRSA in Europe.
Figure 3: Most frequent MRSA clones.
Figure 4: Stages of Staphylococcus aureus infection.
Figure 5: Bacterial targets of antibiotics active against MRSA.

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References

  1. Wertheim, H. F. et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect. Dis. 5, 751–762 (2005).

    PubMed  Google Scholar 

  2. Becker, K. et al. Staphylococcus aureus from the German general population is highly diverse. Int. J. Med. Microbiol. 307, 21–27 (2017).

    CAS  PubMed  Google Scholar 

  3. Kuehnert, M. J. et al. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001–2002. J. Infect. Dis. 193, 172–179 (2006).

    CAS  PubMed  Google Scholar 

  4. Lowy, F. D. Staphylococcus aureus infections. N. Engi J. Med. 339, 520–532 (1998).

    CAS  Google Scholar 

  5. Jevons, M. “Celbenin”-resistant staphylococci. BMJ 1, 124–125 (1961).

    PubMed Central  Google Scholar 

  6. Dzintars, K. in Kucers’ The Use of Antibiotics (eds Grayson, M. et al.) 136–142 (CRC Press, 2018).

    Google Scholar 

  7. Chambers, H. F. & Deleo, F. R. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat. Rev. Microbiol. 7, 629–641 (2009). This is an in-depth review of the clinical and molecular epidemiology of S. aureus, including MRSA, with an emphasis on CA-MRSA.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Faoagali, J. L., Thong, M. L. & Grant, D. Ten years’ experience with methicillin-resistant Staphylococcus aureus in a large Australian hospital. J. Hosp. Infect. 20, 113–119 (1992).

    CAS  PubMed  Google Scholar 

  9. Fridkin, S. K. et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N. Engl. J. Med. 352, 1436–1444 (2005).

    CAS  PubMed  Google Scholar 

  10. Voss, A., Loeffen, F., Bakker, J., Klaassen, C. & Wulf, M. Methicillin-resistant Staphylococcus aureus in pig farming. Emerg. Infect. Dis. 11, 1965–1966 (2005).

    PubMed  PubMed Central  Google Scholar 

  11. Tenover, F. C. et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J. Clin. Microbiol. 33, 2233–2239 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ito, T., Katayama, Y. & Hiramatsu, K. Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrob. Agents Chemother 43, 1449–1458 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Harkins, C. P. et al. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol. 18, 130 (2017).

    PubMed  PubMed Central  Google Scholar 

  14. Diekema, D. J. et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin. Infect. Dis. 32 (Suppl. 2), S114–S132 (2001).

    CAS  PubMed  Google Scholar 

  15. Enright, M. C., Day, N. P., Davies, C. E., Peacock, S. J. & Spratt, B. G. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J. Clin. Microbiol. 38, 1008–1015 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Monecke, S. et al. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS ONE 6, e17936 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. [No authors listed.] European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Controlhttp://ecdc.europa.eu/en/activities/surveillance/EARS-Net/Pages/index.aspx (2018).

  18. Kock, R. et al. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Eurosurveillance 15, 19688 (2010).

    CAS  PubMed  Google Scholar 

  19. Nielsen, K. L. et al. Fitness cost: a bacteriological explanation for the demise of the first international methicillin-resistant Staphylococcus aureus epidemic. J. Antimicrob. Chemother. 67, 1325–1332 (2012).

    CAS  PubMed  Google Scholar 

  20. Rolain, J. M., Abat, C., Brouqui, P. & Raoult, D. Worldwide decrease in methicillin-resistant Staphylococcus aureus: do we understand something? Clin. Microbiol. Infect. 21, 515–517 (2015).

    PubMed  Google Scholar 

  21. Garcia- Alvarez, L., Dawson, S., Cookson, B. & Hawkey, P. Working across the veterinary and human health sectors. J. Antimicrob. Chemother. 67 (Suppl. 1), Í37–Í49 (2012).

    Google Scholar 

  22. van Alen, S. et al. In the centre of an epidemic: fifteen years of LA-MRSA CC398 at the University Hospital Munster. Vet. Microbiol. 200, 19–24 (2017).

    CAS  PubMed  Google Scholar 

  23. Lozano, C. et al. High prevalence of spa types associated with the clonal lineage CC398 among tetracycline-resistant methicillin-resistant Staphylococcus aureus strains in a Spanish hospital. J. Antimicrob. Chemother. 67, 330–334 (2012).

    CAS  PubMed  Google Scholar 

  24. van Cleef, B. A. et al. Livestock-associated methicillin-resistant Staphylococcus aureus in humans, Europe. Emerg. Infect. Dis. 17, 502–505 (2011).

    PubMed  PubMed Central  Google Scholar 

  25. Larsen, J. et al. Meticillin-resistant Staphylococcus aureus CC398 is an increasing cause of disease in people with no livestock contact in Denmark, 1999 to 2011. Eurosurveillance 20, 30021 (2015).

    Google Scholar 

  26. Hetem, D. J., Bootsma, M. C., Troelstra, A. & Bonten, M. J. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus. Emerg. Infect. Dis. 19, 1797–1802 (2013).

    PubMed  Google Scholar 

  27. Styers, D., Sheehan, D. J., Hogan, P. & Sahm, D. F. Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann. Clin. Microbiol. Antimicrob. 5, 2 (2006).

    PubMed  PubMed Central  Google Scholar 

  28. Talan, D. A. et al. Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin. Infect. Dis. 53, 144–149 (2011).

    PubMed  Google Scholar 

  29. Moran, G. J. et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl. J. Med. 355, 666–674 (2006).

    CAS  PubMed  Google Scholar 

  30. Seybold, U. et al. Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin. Infect. Dis. 42, 647–656 (2006).

    CAS  PubMed  Google Scholar 

  31. Popovich, K. J., Weinstein, R. A. & Hota, B. Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains? Clin. Infect. Dis. 46, 787–794 (2008).

    PubMed  Google Scholar 

  32. Planet, P. J. et al. Parallel epidemics of community-associated methicillin-resistant Staphylococcus aureus USA300 infection in North and South America. J. Infect. Dis. 212, 1874–1882 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Von Dach, E. et al. Comparative genomics of community-associated methicillin-resistant Staphylococcus aureus shows the emergence of clone ST8-USA300 in Geneva, Switzerland. J. Infect. Dis. 213, 1370–1379 (2016).

    CAS  PubMed  Google Scholar 

  34. Dantes, R. et al. National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern. Med. 173, 1970–1978 (2013).

    PubMed  Google Scholar 

  35. Jain, R. et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N. Engl. J. Med. 364, 1419–1430 (2011).

    CAS  PubMed  Google Scholar 

  36. Lee, G. M. et al. Effect of nonpayment for preventable infections in U. S. hospitals. N. Engl. J. Med. 367, 1428–1437 (2012).

    CAS  PubMed  Google Scholar 

  37. Chen, C. J. & Huang, Y. C. New epidemiology of Staphylococcus aureus infection in Asia. Clin. Microbiol. Infect. 20, 605–623 (2014).

    CAS  PubMed  Google Scholar 

  38. Mendes, R. E. et al. Regional resistance surveillance program results for 12 Asia-Pacific nations (2011). Antimicrob. Agents Chemother. 57, 5721–5726 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Lai, C. C., Lin, S. H., Sheng, W. H. & Hsueh, P. R. Decrease in the incidence of meticillin-resistant Staphylococcus aureus nosocomial bloodstream infections in Taiwan. Int. J. Antimicrob. Agents 41, 591–592 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. [No authors listed.] Australian Group on Antimicrobial Resistance (AGAR). AGAR Grouphttp://www.agargroup.org.au/ (2018).

  41. Mitchell, B. G., Collignon, P. J., McCann, R., Wilkinson, I. J. & Wells, A. A major reduction in hospital-onset Staphylococcus aureus bacteremia in Australia-12 years of progress: an observational study. Clin. Infect. Dis. 59, 969–975 (2014).

    PubMed  Google Scholar 

  42. Williamson, D. A., Coombs, G. W. & Nimmo, G. R. Staphylococcus aureus ‘Down Under’: contemporary epidemiology of S. aureus in Australia, New Zealand, and the South West Pacific. Clin. Microbiol. Infect. 20, 597–604 (2014).

    CAS  PubMed  Google Scholar 

  43. Falagas, M. E., Karageorgopoulos, D. E., Leptidis, J. & Korbila, I. P. MRSA in Africa: filling the global map of antimicrobial resistance. PLoS ONE 8, e68024 (2013).

    PubMed  PubMed Central  Google Scholar 

  44. Brink, A., Moolman, J., da Silva, M. C., Botha, M. & National Antibiotic Surveillance Forum. Antimicrobial susceptibility profile of selected bacteraemic pathogens from private institutions in South Africa. S. Afr. Med. J. 97, 273–279 (2007).

    CAS  Google Scholar 

  45. Jansen van Rensburg, M. J., Whitelaw, A. C. & Elisha, B. G. Genetic basis of rifampicin resistance in methicillin-resistant Staphylococcus aureus suggests clonal expansion in hospitals in Cape Town, South Africa. BMC Microbiol. 12, 46 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Zervou, F. N., Zacharioudakis, I. M., Ziakas, P. D., Rich, J. D. & Mylonakis, E. Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization in HIV infection: a meta-analysis. Clin. Infect. Dis. 59, 1302–1311 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kluytmans, J., van Belkum, A. & Verbrugh, H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 10, 505–520 (1997). This is a comprehensive review of staphylococcal nasal colonization including its clinical relevance.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Sim, B. L., McBryde, E., Street, A. C. & Marshall, C. Multiple site surveillance cultures as a predictor of methicillin-resistant Staphylococcus aureus infections. Infect. Control Hosp. Epidemiol. 34, 818–824 (2013).

    PubMed  Google Scholar 

  49. Eriksen, N. H., Espersen, F., Rosdahl, V. T. & Jensen, K. Carriage of Staphylococcus aureus among 104 healthy persons during a 19-month period. Epidemiol. Infect. 115, 51–60 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Hoffler, U., Bulanda, M., Heczko, P. B. & Pulverer, G. A comparison of staphylococcal nasal carrier rates in Germany and Poland. Med. Microbiol. Immunol. 164, 285–290 (1978).

    CAS  PubMed  Google Scholar 

  51. Emonts, M. et al. Host polymorphisms in interleukin 4, complement factor H, and C-reactive protein associated with nasal carriage of Staphylococcus aureus and occurrence of boils. J. Infect. Dis. 197, 1244–1253 (2008).

    CAS  PubMed  Google Scholar 

  52. Lucet, J. C. et al. Carriage of methicillin-resistant Staphylococcus aureus in home care settings: prevalence, duration, and transmission to household members. Arch. Intern. Med. 169, 1372–1378 (2009).

    PubMed  Google Scholar 

  53. Burian, M. et al. Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization. J. Infect. Dis. 201, 1414–1421 (2010).

    CAS  PubMed  Google Scholar 

  54. Weidenmaier, C. et al. Differential roles of sortase-anchored surface proteins and wall teichoic acid in Staphylococcus aureus nasal colonization. Int. J. Med. Microbiol. 298, 505–513 (2008).

    CAS  PubMed  Google Scholar 

  55. Wertheim, H. F. et al. Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans. PLoS Med. 5, e17 (2008).

    PubMed  PubMed Central  Google Scholar 

  56. O’Brien, L. M., Walsh, E. J., Massey, R. C., Peacock, S. J. & Foster, T. J. Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization. Cell. Microbiol. 4, 759–770 (2002).

    PubMed  Google Scholar 

  57. Liu, C. M. et al. Staphylococcus aureus and the ecology of the nasal microbiome. Sci. Adv. 1, e1400216 (2015).

    PubMed  PubMed Central  Google Scholar 

  58. Lemon, K. P. et al. Comparative analyses of the bacterial microbiota of the human nostril and oropharynx. mBio 1, e00129–10 (2010).

    PubMed  PubMed Central  Google Scholar 

  59. Krismer, B. et al. Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation in the human nose. PLoS Pathog. 10, e1003862 (2014).

    PubMed  PubMed Central  Google Scholar 

  60. Zipperer, A. et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535, 511–516 (2016).

    CAS  PubMed  Google Scholar 

  61. Kaspar, U. et al. The culturome of the human nose habitats reveals individual bacterial fingerprint patterns. Environ. Microbiol. 18, 2130–2142 (2016).

    CAS  PubMed  Google Scholar 

  62. Krismer, B., Weidenmaier, C., Zipperer, A. & Peschel, A. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat. Rev. Microbiol. 15, 675–687 (2017). This review provides a detailed discussion of the complex interplay between S. aureus and other organisms that form part of the nasal microbiota.

    CAS  PubMed  Google Scholar 

  63. Boyle-Vavra, S. et al. USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a capsular polysaccharide due to conserved mutations in the cap5 locus. mBio 6, e02585–14 (2015).

    PubMed  PubMed Central  Google Scholar 

  64. Spaan, A. N., van Strijp, J. A. G. & Torres, V. J. Leukocidins: staphylococcal bi-component pore-forming toxins find their receptors. Nat. Rev. Microbiol. 15, 435–447 (2017). This is a comprehensive overview of the various pore-forming protein toxins and their cognate host receptors.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Laabei, M. et al. Predicting the virulence of MRSA from its genome sequence. Genome Res. 24, 839–849 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Thammavongsa, V., Kim, H. K., Missiakas, D. & Schneewind, O. Staphylococcal manipulation of host immune responses. Nat. Rev. Microbiol. 13, 529–543 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Recker, M. et al. Clonal differences in Staphylococcus aureus bacteraemia-associated mortality. Nat. Microbiol. 2, 1381–1388 (2017). This paper reveals how different S. aureus lineages have adopted different strategies to overcome host responses and cause severe pathology.

    CAS  PubMed  Google Scholar 

  68. Kluytmans, J. A. et al. Nasal carriage of Staphylococcus aureus as a major risk factor for wound infections after cardiac surgery. J. Infect. Dis. 171, 216–219 (1995).

    CAS  PubMed  Google Scholar 

  69. von Eiff, C., Becker, K., Machka, K., Stammer, H. & Peters, G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med. 344, 11–16 (2001).

    CAS  PubMed  Google Scholar 

  70. Foster, T. J., Geoghegan, J. A., Ganesh, V. K. & Hook, M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49–62 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Vanhommerig, E. et al. Comparison of biofilm formation between major clonal lineages of methicillin resistant Staphylococcus aureus. PLoS ONE 9, e104561 (2014).

    PubMed  PubMed Central  Google Scholar 

  72. Spaan, A. N., Surewaard, B. G., Nijland, R. & van Strijp, J. A. Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu. Rev. Microbiol. 67, 629–650 (2013).

    CAS  PubMed  Google Scholar 

  73. Hanzelmann, D. et al. Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants. Nat. Commun. 7, 12304 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Cheng, A. G., DeDent, A. C., Schneewind, O. & Missiakas, D. A play in four acts: Staphylococcus aureus abscess formation. Trends Microbiol. 19, 225–232 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Laarman, A., Milder, F., van Strijp, J. & Rooijakkers, S. Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications. J. Mol. Med. 88, 115–120 (2010).

    CAS  PubMed  Google Scholar 

  76. Stapels, D. A. et al. Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors. Proc. Natl Acad. Sci. USA 111, 13187–13192 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Peschel, A. & Sahl, H. G. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat. Rev. Microbiol. 4, 529–536 (2006).

    CAS  PubMed  Google Scholar 

  78. Loffler, B. et al. Staphylococcus aureus panton–valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog. 6, e1000715 (2010).

    PubMed  PubMed Central  Google Scholar 

  79. Spaulding, A. R. et al. Staphylococcal and streptococcal superantigen exotoxins. Clin. Microbiol. Rev. 26, 422–447 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Chavakis, T., Wiechmann, K., Preissner, K. T. & Herrmann, M. Staphylococcus aureus interactions with the endothelium: the role of bacterial “secretable expanded repertoire adhesive molecules” (SERAM) in disturbing host defense systems. Thromb. Haemost. 94, 278–285 (2005).

    CAS  PubMed  Google Scholar 

  81. Weidenmaier, C. et al. Lack of wall teichoic acids in Staphylococcus aureus leads to reduced interactions with endothelial cells and to attenuated virulence in a rabbit model of endocarditis. J. Infect. Dis. 191, 1771–1777 (2005).

    CAS  PubMed  Google Scholar 

  82. Loffler, B., Tuchscherr, L., Niemann, S. & Peters, G. Staphylococcus aureus persistence in non-professional phagocytes. Int. J. Med. Microbiol. 304, 170–176 (2014).

    PubMed  Google Scholar 

  83. Thomer, L., Schneewind, O. & Missiakas, D. Pathogenesis of Staphylococcus aureus bloodstream infections. Annu. Rev. Pathol. 11, 343–364 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Le, K. Y. & Otto, M. Quorum-sensing regulation in staphylococci-an overview. Front. Microbiol. 6, 1174 (2015).

    PubMed  PubMed Central  Google Scholar 

  85. Cheung, G. Y., Wang, R., Khan, B. A., Sturdevant, D. E. & Otto, M. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect. Immun. 79, 1927–1935 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kaito, C. et al. Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence. PLoS Pathog. 9, e1003269 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Painter, K. L., Krishna, A., Wigneshweraraj, S. & Edwards, A. M. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia? Trends Microbiol. 22, 676–685 (2014).

    CAS  PubMed  Google Scholar 

  88. Crisostomo, M. I. et al. The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones. Proc. Natl Acad. Sci. USA 98, 9865–9870 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC). Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob. Agents Chemother. 53, 4961–4967 (2009). This paper describes the main SCCmec types and the nomenclature to be followed for the naming of new SCCmec types.

    Google Scholar 

  90. Bal, A. M. et al. Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin-resistant Staphylococcus aureus: Blurring of the traditional definitions. J. Glob. Antimicrob. Resist 6, 95–101 (2016).

    CAS  PubMed  Google Scholar 

  91. Hartman, B. J. & Tomasz, A. Low-affinity penicillin-binding protein associated with beta-lactam resistance in Staphylococcus aureus. J. Bacteriol. 158, 513–516 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Garcia-Alvarez, L. et al. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect. Dis. 11, 595–603 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Kim, C. et al. Properties of a novel PBP2A protein homolog from Staphylococcus aureus strain LGA251 and its contribution to the beta-lactam-resistant phenotype. J. Biol. Chem. 287, 36854–36863 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Milheirico, C., de Lencastre, H. & Tomasz, A. Full-genome sequencing identifies in the genetic background several determinants that modulate the resistance phenotype in methicillin-resistant Staphylococcus aureus strains carrying the novel mecC gene. Antimicrob. Agents Chemother. 61, e02500–16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Becker, K. et al. Plasmid-encoded transferable mecB-mediated methicillin resistance in Staphylococcus aureus. Emerg. Infect. Dis. 24, 242–248 (2018).

    CAS  PubMed  Google Scholar 

  96. Hiramatsu, K., Asada, K., Suzuki, E., Okonogi, K. & Yokota, T. Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA). FEBSLett. 298, 133–136 (1992).

    CAS  Google Scholar 

  97. Arede, P., Milheirico, C., de Lencastre, H. & Oliveira, D. C. The anti-repressor MecR2 promotes the proteolysis of the mecA repressor and enables optimal expression of beta-lactam resistance in MRSA. PLoS Pathog. 8, e1002816 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Zhang, H. Z., Hackbarth, C. J., Chansky, K. M. & ≈Chambers, H. F. A proteolytic transmembrane signaling pathway and resistance to beta-lactams in staphylococci. Science 291, 1962–1965 (2001).

    CAS  PubMed  Google Scholar 

  99. De Lencastre, H. et al. Antibiotic resistance as a stress response: complete sequencing of a large number of chromosomal loci in Staphylococcus aureus strain COL that impact on the expression of resistance to methicillin. Microb. Drug Resist 5, 163–175 (1999).

    PubMed  Google Scholar 

  100. Kim, C. et al. The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response. PLoS ONE 8, e82814 (2013).

    PubMed  PubMed Central  Google Scholar 

  101. Boyle-Vavra, S., Yin, S. & Daum, R. S. The VraS/VraR two-component regulatory system required for oxacillin resistance in community-acquired methicillin-resistant Staphylococcus aureus. FEMS Microbiol. Lett. 262, 163–171 (2006).

    CAS  PubMed  Google Scholar 

  102. Jousselin, A. et al. The Staphylococcus aureus chaperone PrsA is a new auxiliary factor of oxacillin resistance affecting penicillin-binding protein 2A. Antimicrob. Agents Chemother 60, 1656–1666 (2015).

    PubMed  Google Scholar 

  103. Kim, C. K., Milheirico, C., de Lencastre, H. & Tomasz, A. Antibiotic resistance as a stress response: recovery of high-level oxacillin resistance in methicillin-resistant Staphylococcus aureus “Auxiliary” (fem) mutants by induction of the stringent stress response. Antimicrob. Agents Chemother 61, e00313-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  104. Gardete, S. & Tomasz, A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J. Clin. Invest. 124, 2836–2840 (2014). This is a comprehensive review of the mechanisms of vancomycin resistance in S. aureus.

    PubMed  Google Scholar 

  105. Klevens, R. M. et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298, 1763–1771 (2007).

    CAS  PubMed  Google Scholar 

  106. Epstein, L. et al. Risk factors for invasive methicillin-resistant Staphylococcus aureus infection after recent discharge from an acute-care hospitalization, 2011–2013. Clin. Infect. Dis. 62, 45–52 (2016).

    PubMed  Google Scholar 

  107. Davis, K. A., Stewart, J. J., Crouch, H. K., Florez, C. E. & Hospenthal, D. R. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection. Clin. Infect. Dis. 39, 776–782 (2004).

    PubMed  Google Scholar 

  108. Francis, J. S. et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton–Valentine leukocidin genes. Clin. Infect. Dis. 40, 100–107 (2005).

    PubMed  Google Scholar 

  109. Miller, L. G. et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N. Engl. J. Med. 352, 1445–1453 (2005).

    CAS  PubMed  Google Scholar 

  110. Kazakova, S. V. et al. A clone of methicillin-resistant Staphylococcus aureus among professional football players. N. Engl. J. Med. 352, 468–475 (2005).

    CAS  PubMed  Google Scholar 

  111. Aiello, A. E., Lowy, F. D., Wright, L. N. & Larson, E. L. Meticillin-resistant Staphylococcus aureus among US prisoners and military personnel: review and recommendations for future studies. Lancet Infect. Dis. 6, 335–341 (2006).

    PubMed  Google Scholar 

  112. Drougka, E. et al. A 12-year survey of methicillin-resistant Staphylococcus aureus infections in Greece: ST80-IV epidemic? Clin. Microbiol. Infect. 20, O796–803 (2014).

    CAS  PubMed  Google Scholar 

  113. Clinical and Laboratory Standards Institute. M100-S23. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Third Informational Supplement (CLSI, 2013).

  114. Ryffel, C., Strassle, A., Kayser, F. H. & Berger-Bachi, B. Mechanisms of heteroresistance in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 38, 724–728 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Penn, C. et al. Wound infections caused by inducible meticillin-resistant Staphylococcus aureus strains. J. Glob. Antimicrob. Resist 1, 79–83 (2013).

    PubMed  Google Scholar 

  116. Winstanley, T. & Courvalin, P. Expert systems in clinical microbiology. Clin. Microbiol. Rev. 24, 515–556 (2011). This reference is a good overview of automated systems for the detection of resistance mechanisms with a critical review of published evaluations of the performance of each system.

    PubMed  PubMed Central  Google Scholar 

  117. Bhowmick, T. et al. Controlled multicenter evaluation of a bacteriophage-based method for rapid detection of Staphylococcus aureus in positive blood cultures. J. Clin. Microbiol. 51, 1226–1230 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Opota, O., Croxatto, A., Prod’hom, G. & Greub, G. Blood culture-based diagnosis of bacteraemia: state of the art. Clin. Microbiol. Infect. 21, 313–322 (2015).

    CAS  PubMed  Google Scholar 

  119. Romero-Gomez, M. P., Cendejas-Bueno, E., Garcia Rodriguez, J. & Mingorance, J. Impact of rapid diagnosis of Staphylococcus aureus bacteremia from positive blood cultures on patient management. Eur. J. Clin. Microbiol. Infect. Dis. 36, 2469–2473 (2017).

    CAS  PubMed  Google Scholar 

  120. Malhotra-Kumar, S. et al. Current trends in rapid diagnostics for methicillin-resistant Staphylococcus aureus and glycopeptide-resistant enterococcus species. J. Clin. Microbiol. 46, 1577–1587 (2008).

    PubMed  PubMed Central  Google Scholar 

  121. Malhotra- Kumar, S. et al. Evaluation of molecular assays for rapid detection of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 48, 4598–4601 (2010).

    Google Scholar 

  122. Blaschke, A. J. et al. Rapid identification of pathogens from positive blood cultures by multiplex polymerase chain reaction using the FilmArray system. Diagnost. Microbiol. Infect. Dis. 74, 349–355 (2012).

    CAS  Google Scholar 

  123. Almuhayawi, M., Altun, O., Stralin, K. & Ozenci, V. Identification of microorganisms by FilmArray and matrix-assisted laser desorption ionization-time of flight mass spectrometry prior to positivity in the blood culture system. J. Clin. Microbiol. 52, 3230–3236 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Cao, M. D. et al. Streaming algorithms for identification of pathogens and antibiotic resistance potential from real-time MinION(TM) sequencing. GigaScience 5, 32 (2016).

    PubMed  PubMed Central  Google Scholar 

  125. Aanensen, D. M. et al. Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcus aureus in Europe. mBio 7, e00444-16 (2016).

    PubMed  PubMed Central  Google Scholar 

  126. Koser, C. U. et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N. Engl. J. Med. 366, 2267–2275 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Millar, E. V. et al. Genomic characterization of USA300 methicillin-resistant Staphylococcus aureus (MRSA) to evaluate intraclass transmission and recurrence of skin and soft tissue infection (SSTI) among high-risk military trainees. Clin. Infect. Dis. 65, 461–468 (2017).

    PubMed  PubMed Central  Google Scholar 

  128. Merlino, J., Leroi, M., Bradbury, R., Veal, D. & Harbour, C. New chromogenic identification and detection of Staphylococcus aureus and methicillin-resistant S. aureus. J. Clin. Microbiol. 38, 2378–2380 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Perry, J. D. A. Decade of development of chromogenic culture media for clinical microbiology in an era of molecular diagnostics. Clin. Microbiol. Rev. 30, 449–479 (2017). Tqhis is a comprehensive reference reviewing rapid culture methods for the detection of MRSA and other multidrug-resistant organisms.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Gazin, M. et al. Culture-based detection of methicillin-resistant Staphylococcus aureus by a network of European laboratories: an external quality assessment study. Eur. J. Clin. Microbiol. Infect. Dis. 31, 1765–1770 (2012).

    CAS  PubMed  Google Scholar 

  131. Luthje, P. et al. Identification of microorganisms grown on chromogenic media by MALDI-TOF MS. J. Microbiol. Methods 136, 17–20 (2017).

    CAS  PubMed  Google Scholar 

  132. Faron, M. L. et al. Automated scoring of chromogenic media for detection of methicillin-resistant Staphylococcus aureus by use of WASPLab image analysis software. J. Clin. Microbiol. 54, 620–624 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Cunningham, R. et al. Effect on MRSA transmission of rapid PCR testing of patients admitted to critical care. J. Hosp. Infect. 65, 24–28 (2007).

    CAS  PubMed  Google Scholar 

  134. Derde, L. P. G. et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect. Dis. 14, 31–39 (2014).

    PubMed  PubMed Central  Google Scholar 

  135. Wu, P. J., Jeyaratnam, D., Tosas, O., Cooper, B. S. & French, G. L. Point-of-care universal screening for meticillin-resistant Staphylococcus aureus: a cluster-randomized cross-over trial. J. Hosp. Infect. 95, 245–252 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Calfee, D. P. et al. Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update. Infect. Control Hosp. Epidemiol. 35, 772–796 (2014). This paper is an expert guidance document, with grading of the quality of the evidence, for MRSA control in acute care facilities.

    PubMed  Google Scholar 

  137. World Health Organization. WHO Guidelines on Hand Hygiene in Health Care. World Alliance for Patient Safety (WHO Press, Geneva, 2009).

  138. Sax, H. et al. ‘My five moments for hand hygiene’: a user-centred design approach to understand, train, monitor and report hand hygiene. J. Hosp. Infect. 67, 9–21 (2007).

    CAS  PubMed  Google Scholar 

  139. Pittet, D. et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Lancet 356, 1307–1312 (2000).

    CAS  PubMed  Google Scholar 

  140. Stone, S. P. et al. Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study. BMJ 344, e3005 (2012).

    PubMed  PubMed Central  Google Scholar 

  141. Salgado, C. D. & Farr, B. M. What proportion of hospital patients colonized with methicillin-resistant Staphylococcus aureus are identified by clinical microbiological cultures? Infect. Control Hosp. Epidemiol. 27, 116–121 (2006).

    PubMed  Google Scholar 

  142. Robicsek, A. et al. Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Ann. Intern. Med. 148, 409–418 (2008).

    PubMed  Google Scholar 

  143. Harbarth, S. et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA 299, 1149–1157 (2008).

    CAS  PubMed  Google Scholar 

  144. Lee, A. S. et al. Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial. BMJ Open 3, e003126 (2013).

    PubMed  PubMed Central  Google Scholar 

  145. Robotham, J. V. et al. Cost-effectiveness of national mandatory screening of all admissions to English National Health Service hospitals for meticillin-resistant Staphylococcus aureus: a mathematical modelling study. Lancet Infect. Dis. 16, 348–356 (2016).

    PubMed  Google Scholar 

  146. Huskins, W. C. et al. Intervention to reduce transmission of resistant bacteria in intensive care. N. Engl. J. Med. 364, 1407–1418 (2011).

    PubMed  PubMed Central  Google Scholar 

  147. Derde, L. P. et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect. Dis. 14, 31–39 (2014).

    PubMed  PubMed Central  Google Scholar 

  148. Harris, A. D. et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial. JAMA 310, 1571–1580 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Cepeda, J. A. et al. Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective two-centre study. Lancet 365, 295–304 (2005).

    PubMed  Google Scholar 

  150. Fatkenheuer, G., Hirschel, B. & Harbarth, S. Screening and isolation to control meticillin-resistant Staphylococcus aureus: sense, nonsense, and evidence. Lancet 385, 1146–1149 (2015). This commentary provides an update regarding the growing evidence for and against the role of active surveillance in MRSA control.

    PubMed  Google Scholar 

  151. Loeb, M., Main, C., Walker-Dilks, C. & Eady, A. Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization. Cochrane Database Syst. Rev. 4, CD003340 (2003).

    Google Scholar 

  152. Poovelikunnel, T., Gethin, G. & Humphreys, H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J. Antimicrob. Chemother. 70, 2681–2692 (2015).

    CAS  PubMed  Google Scholar 

  153. Landelle, C. et al. Randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy of polyhexanide for topical decolonization of MRSA carriers. J. Antimicrob. Chemother. 71, 531–538 (2016).

    CAS  PubMed  Google Scholar 

  154. Bode, L. G. et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med. 362, 9–17 (2010).

    CAS  PubMed  Google Scholar 

  155. van Rijen, M. M., Bode, L. G., Baak, D. A., Kluytmans, J. A. & Vos, M. C. Reduced costs for Staphylococcus aureus carriers treated prophylactically with mupirocin and chlorhexidine in cardiothoracic and orthopaedic surgery. PLoS ONE 7, e43065 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Huang, S. S. et al. Targeted versus universal decolonization to prevent ICU infection. N. Engl. J. Med. 368, 2255–2265 (2013).

    CAS  PubMed  Google Scholar 

  157. Ammerlaan, H. S. et al. Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness of a national guideline. J. Antimicrob. Chemother. 66, 2409–2417 (2011).

    CAS  PubMed  Google Scholar 

  158. Ammerlaan, H. S. et al. Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of treatment failure. J. Antimicrob. Chemother. 66, 2418–2424 (2011).

    CAS  PubMed  Google Scholar 

  159. Talan, D. A. et al. Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N. Engl. J. Med. 374, 823–832 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Daum, R. S. et al. A placebo-controlled trial of antibiotics for smaller skin abscesses. N. Engl. J. Med. 376, 2545–2555 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Liu, C. et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin. Infect. Dis. 52, e18–55 (2011). This paper represents an essential and up-to-date guidance document for management of MRSA infection.

    PubMed  Google Scholar 

  162. Gould, I. M. et al. New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. Int. J. Antimicrob. Agents 39, 96–104 (2012).

    CAS  PubMed  Google Scholar 

  163. Svetitsky, S., Leibovici, L. & Paul, M. Comparative efficacy and safety of vancomycin versus teicoplanin: systematic review and meta-analysis. Antimicrob. Agents Chemother. 53, 4069–4079 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Vandecasteele, S. J., De Vriese, A. S. & Tacconelli, E. The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties. J. Antimicrob. Chemother. 68, 743–748 (2013).

    CAS  PubMed  Google Scholar 

  165. Lodise, T. P., Patel, N., Lomaestro, B. M., Rodvold, K. A. & Drusano, G. L. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin. Infect. Dis. 49, 507–514 (2009).

    CAS  PubMed  Google Scholar 

  166. Cataldo, M. A., Tacconelli, E., Grilli, E., Pea, F. & Petrosillo, N. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J. Antimicrob. Chemother. 67, 17–24 (2012).

    CAS  PubMed  Google Scholar 

  167. Bradley, J. S. Which antibiotic for resistant Gram-positives, and why? J. Infect. 68 (Suppl. 1), S63–75 (2014).

    PubMed  Google Scholar 

  168. Falagas, M. E. & Vardakas, K. Z. Benefit-risk assessment of linezolid for serious gram-positive bacterial infections. DrugSaf. 31, 753–768 (2008).

    CAS  Google Scholar 

  169. Cosgrove, S. E. et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin. Infect. Dis. 36, 53–59 (2003).

    PubMed  Google Scholar 

  170. Fowler, V. G. Jr. et al. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch. Intern. Med. 163, 2066–2072 (2003).

    PubMed  Google Scholar 

  171. Thwaites, G. E. et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect. Dis. 11, 208–222 (2011). This is an important reference for all persons interested in the optimal treatment of S. aureus bacteraemia.

    PubMed  Google Scholar 

  172. Houlihan, H. H., Mercier, R. C. & Rybak, M. J. Pharmacodynamics of vancomycin alone and in combination with gentamicin at various dosing intervals against methicillin-resistant Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model. Antimicrob. Agents Chemother. 41, 2497–2501 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Tsuji, B. T. & Rybak, M. J. Short-course gentamicin in combination with daptomycin or vancomycin against Staphylococcus aureus in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob. Agents Chemother. 49, 2735–2745 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Rehm, S. J. et al. Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates. J. Antimicrob. Chemother. 62, 1413–1421 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Fowler, V. G. Jr. et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N. Engl. J. Med. 355, 653–665 (2006).

    CAS  PubMed  Google Scholar 

  176. Bayer, A. S. & Murray, B. E. Initial low-dose aminoglycosides in Staphylococcus aureus bacteremia: good science, urban legend, or just plain toxic? Clin. Infect. Dis. 48, 722–724 (2009).

    PubMed  Google Scholar 

  177. Forrest, G. N. & Tamura, K. Rifampin combination therapy for nonmycobacterial infections. Clin. Microbiol. Rev. 23, 14–34 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Thwaites, G. E. et al. Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 391, 668–678 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Davis, J. S. et al. Combination of vancomycin and beta-lactam therapy for methicillin-resistant Staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial. Clin. Infect. Dis. 62, 173–180 (2016).

    CAS  PubMed  Google Scholar 

  180. Sakoulas, G. et al. Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline. Clin. Ther. 36, 1317–1333 (2014).

    CAS  PubMed  Google Scholar 

  181. Rose, W. E., Berti, A. D., Hatch, J. B. & Maki, D. G. Relationship of in vitro synergy and treatment outcome with daptomycin plus rifampin in patients with invasive methicillin-resistant Staphylococcus aureus infections. Antimicrob. Agents Chemother. 57, 3450–3452 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Cosimi, R. A., Beik, N., Kubiak, D. W. & Johnson, J. A. Ceftaroline for severe methicillin-resistant Staphylococcus aureus infections: a systematic review. Open Forum Infect. Dis. 4, ofx084 (2017).

    PubMed  PubMed Central  Google Scholar 

  183. Tattevin, P., Basuino, L., Bauer, D., Diep, B. A. & Chambers, H. F. Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 54, 610–613 (2010).

    CAS  PubMed  Google Scholar 

  184. Oltolini, C. et al. Meticillin-resistant Staphylococcus aureus endocarditis: first report of daptomycin plus ceftobiprole combination as salvage therapy. Int. J. Antimicrob. Agents 47, 502–504 (2016).

    CAS  PubMed  Google Scholar 

  185. Andrey, D. O. et al. Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013–2014 at the Geneva University Hospitals. Eur. J. Clin. Microbiol. Infect. Dis. 36, 343–350 (2017).

    CAS  PubMed  Google Scholar 

  186. Long, S. W. et al. PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus isolates. Antimicrob. Agents Chemother. 58, 6668–6674 (2014).

    PubMed  PubMed Central  Google Scholar 

  187. Mendes, R. E. et al. Characterization of methicillin-resistant Staphylococcus aureus displaying increased MICs of ceftaroline. J. Antimicrob. Chemother. 67, 1321–1324 (2012).

    CAS  PubMed  Google Scholar 

  188. Zhanel, G. G. et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs 70, 859–886 (2010).

    CAS  PubMed  Google Scholar 

  189. McCurdy, S. P., Jones, R. N., Mendes, R. E., Puttagunta, S. & Dunne, M. W. In vitro activity of dalbavancin against drug-resistant Staphylococcus aureus isolates from a global surveillance program. Antimicrob. Agents Chemother. 59, 5007–5009 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Werth, B. J. et al. Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen. Clin. Microbiol. Infect. 24, 429.e1–429.e5 (2018).

    CAS  Google Scholar 

  191. Yaw, L. K., Robinson, J. O. & Ho, K. M. A comparison of long-term outcomes after meticillin-resistant and meticillin-sensitive Staphylococcus aureus bacteraemia: an observational cohort study. Lancet Infect. Dis. 14, 967–975 (2014).

    PubMed  Google Scholar 

  192. Fatkenheuer, G. & Kaasch, A. J. How deadly is meticillin-resistant Staphylococcus aureus? Lancet Infect. Dis. 14, 905–907 (2014).

    Google Scholar 

  193. De Angelis, G. et al. Multistate modelling to estimate the excess length of stay associated with meticillin-resistant Staphylococcus aureus colonisation and infection in surgical patients. J. Hosp. Infect. 78, 86–91 (2011).

    CAS  PubMed  Google Scholar 

  194. De Angelis, G., Murthy, A., Beyersmann, J. & Harbarth, S. Estimating the impact of healthcare-associated infections on length of stay and costs. Clin. Microbiol. Infect. 16, 1729–1735 (2010).

    CAS  PubMed  Google Scholar 

  195. Stewardson, A. J. et al. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. Eurosurveillance 21, 30319 (2016). This is a methodologically sound analysis of excess length of stay of MRSA bacteraemia.

    PubMed Central  Google Scholar 

  196. Haessler, S., Mackenzie, T. & Kirkland, K. B. Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus. J. Hosp. Infect. 69, 39–45 (2008).

    CAS  PubMed  Google Scholar 

  197. Pendleton, A. & Kocher, M. S. Methicillin-resistant Staphylococcus aureus bone and joint infections in children. J. Am. Acad. Orthop. Surg. 23, 29–37 (2015).

    PubMed  Google Scholar 

  198. Salgado, C. D., Dash, S., Cantey, J. R. & Marculescu, C. E. Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clin. Orthop. Relat. Res. 461, 48–53 (2007).

    PubMed  Google Scholar 

  199. Gleeson, A., Larkin, P. & O'Sullivan, N. The impact of meticillin-resistant Staphylococcus aureus on patients with advanced cancer and their family members: a qualitative study. Palliat. Med. 30, 382–391 (2016).

    PubMed  Google Scholar 

  200. van Cleef, B. A. et al. Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistant Staphylococcus aureus. Epidemiol. Infect. 144, 1774–1783 (2016).

    CAS  PubMed  Google Scholar 

  201. Ammerlaan, H. S. et al. Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin. Infect. Dis. 56, 798–805 (2013). This is most likely the best paper evaluating the question of whether MRSA adds to the overall burden of nosocomial infections.

    CAS  PubMed  Google Scholar 

  202. Jones, B. E. et al. Variation in empiric coverage versus detection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in hospitalizations for community-onset pneumonia across 128 US veterans affairs medical centers. Infect. Control Hosp. Epidemiol. 38, 937–944 (2017).

    PubMed  Google Scholar 

  203. Herr, C. E., Heckrodt, T. H., Hofmann, F. A., Schnettler, R. & Eikmann, T. F. Additional costs for preventing the spread of methicillin-resistant Staphylococcus aureus and a strategy for reducing these costs on a surgical ward. Infect. Control Hosp. Epidemiol. 24, 673–678 (2003).

    PubMed  Google Scholar 

  204. Wertheim, H. F. et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 364, 703–705 (2004).

    PubMed  Google Scholar 

  205. Pozzi, C. et al. Vaccines for Staphylococcus aureus and target populations. Curr. Top. Microbiol. Immunol. 409, 491–528 (2017).

    CAS  PubMed  Google Scholar 

  206. Fowler, V. G. et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA 309, 1368–1378 (2013).

    CAS  PubMed  Google Scholar 

  207. Shinefield, H. et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N. Engl. J. Med. 346, 491–496 (2002).

    PubMed  Google Scholar 

  208. Fowler, V. G. Jr & Proctor, R. A. Where does a Staphylococcus aureus vaccine stand? Clin. Microbiol. Infect. 20 (Suppl. 5), 66–75 (2014).

    PubMed  PubMed Central  Google Scholar 

  209. Stentzel, S. et al. Specific serum IgG at diagnosis of Staphylococcus aureus bloodstream invasion is correlated with disease progression. J. Proteom. 128, 1–7 (2015).

    CAS  Google Scholar 

  210. Kurokawa, K., Takahashi, K. & Lee, B. L. The staphylococcal surface-glycopolymer wall teichoic acid (WTA) is crucial for complement activation and immunological defense against Staphylococcus aureus infection. Immunobiology 221, 1091–1101 (2016).

    CAS  PubMed  Google Scholar 

  211. Bekeredjian-Ding, I. Deciphering the significance of the T cell response to Staphylococcus aureus. Future Microbiol. 12, 1023–1026 (2017).

    CAS  PubMed  Google Scholar 

  212. Lehar, S. M. et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323–328 (2015).

    CAS  PubMed  Google Scholar 

  213. World Health Organization. Prioritization of Pathogens to Guide Discovery, Research and Development of New Antibiotics for Drug-Resistant Bacterial Infections, Including Tuberculosis (WHO, Geneva, 2017).

  214. Idelevich, E. A. et al. In vitro activity against Staphylococcus aureus of a novel antimicrobial agent, PRF-119, a recombinant chimeric bacteriophage endolysin. Antimicrob. Agents Chemother. 55, 4416–4419 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. Hiramatsu, K. et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemother. 40, 135–136 (1997).

    CAS  PubMed  Google Scholar 

  216. Mwangi, M. M. et al. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. Proc. Natl Acad. Sci. USA 104, 9451–9456 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Howden, B. P., Davies, J. K., Johnson, P. D., Stinear, T. P. & Grayson, M. L. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin. Microbiol. Rev. 23, 99–139 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  218. Khatib, R. et al. Relevance of vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia. J. Antimicrob. Chemother. 66, 1594–1599 (2011).

    CAS  PubMed  Google Scholar 

  219. Satola, S. W. et al. Clinical and laboratory characteristics of invasive infections due to methicillin-resistant Staphylococcus aureus isolates demonstrating a vancomycin MIC of 2 micrograms per milliliter: lack of effect of heteroresistant vancomycin-intermediate S. aureus phenotype. J. Clin. Microbiol. 49, 1583–1587 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  220. Sievert, D. M. et al. Vancomycin-resistant Staphylococcus aureus in the United States, 2002–2006. Clin. Infect. Dis. 46, 668–674 (2008).

    CAS  PubMed  Google Scholar 

  221. Weigel, L. M. et al. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302, 1569–1571 (2003).

    CAS  PubMed  Google Scholar 

  222. Foucault, M. L., Courvalin, P. & Grillot-Courvalin, C. Fitness cost of VanA-type vancomycin resistance in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53, 2354–2359 (2009).

    CAS  PubMed  Google Scholar 

  223. Stefani, S. et al. Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods. Int. J. Antimicrob. Agents 39, 273–282 (2012).

    CAS  PubMed  Google Scholar 

  224. Carlet, J. et al. French national program for prevention of healthcare-associated infections and antimicrobial resistance, 1992-2008: positive trends, but perseverance needed. Infect. Control Hosp. Epidemiol. 30, 737–745 (2009).

    PubMed  Google Scholar 

  225. Duerden, B., Fry, C., Johnson, A. P. & Wilcox, M. H. The control of methicillin-resistant Staphylococcus aureus blood stream infections in England. Open Forum Infect. Dis. 2, ofv035 (2015).

    PubMed  PubMed Central  Google Scholar 

  226. [No authors listed.] PubMLST. University of Oxfordhttps://pubmlst.org/ (2018).

  227. Thurlow, L. R., Joshi, G. S. & Richardson, A. R. Virulence strategies of the dominant USA300 lineage of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). FEMS Immunol. Med. Microbiol. 65, 5–22 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Peschel, A. & Otto, M. Phenol-soluble modulins and staphylococcal infection. Nat. Rev. Microbiol. 11, 667–673 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  229. Wright, G. D. Q&A: Antibiotic resistance: where does it come from and what can we do about it? BMC Biol. 8, 123 (2010).

    PubMed  PubMed Central  Google Scholar 

  230. McCarthy, A. J. & Lindsay, J. A. Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study. Infect. Genet. Evol. 19, 7–14 (2013).

    CAS  PubMed  Google Scholar 

  231. Markowitz, N., Quinn, E. L. & Saravolatz, L. D. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann. Intern. Med. 117, 390–398 (1992).

    CAS  PubMed  Google Scholar 

  232. Landersdorfer, C. B., Bulitta, J. B., Kinzig, M., Holzgrabe, U. & Sorgel, F. Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations. Clin. Pharmacokinet. 48, 89–124 (2009).

    CAS  PubMed  Google Scholar 

  233. Sakoulas, G., Alder, J., Thauvin-Eliopoulos, C., Moellering, R. C. Jr & Eliopoulos, G. M. Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin. Antimicrob. Agents Chemother. 50, 1581–1585 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  234. Pertel, P. E. et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin. Infect. Dis. 46, 1142–1151 (2008).

    CAS  PubMed  Google Scholar 

  235. Fenton, C., Keating, G. M. & Curran, M. P. Daptomycin. Drugs 64, 445–455 (2004).

    CAS  PubMed  Google Scholar 

  236. Pea, F. et al. Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J. Antimicrob. Chemother. 67, 2034–2042 (2012).

    CAS  PubMed  Google Scholar 

  237. Itani, K. M. et al. Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus. Am. J. Surg. 199, 804–816 (2010).

    CAS  PubMed  Google Scholar 

  238. Corey, G. R. et al. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J. Antimicrob. Chemother. 65 (Suppl. 4), iv41–iv51 (2010).

    CAS  PubMed  Google Scholar 

  239. Wilcox, M. H. et al. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J. Antimicrob. Chemother. 65 (Suppl. 4), iv53–iv65 (2010).

    CAS  PubMed  Google Scholar 

  240. Dryden, M., Zhang, Y., Wilson, D., Iaconis, J. P. & Gonzalez, J. A. Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. J. Antimicrob. Chemother. 71, 3575–3584 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Noel, G. J., Bush, K., Bagchi, P., Ianus, J. & Strauss, R. S. A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections. Clin. Infect. Dis. 46, 647–655 (2008).

    PubMed  Google Scholar 

  242. [No authors listed.] Vibativ (telavancin) [prescribing information]. Astellashttp://www.astellas.us/docs/us/VIBATIV_PI_Final.pdf (2009).

  243. Rubinstein, E. et al. Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin. Infect. Dis. 52, 31–40 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  244. Stryjewski, M. E. et al. A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study. BMC Infect. Dis. 14, 289 (2014).

    PubMed  PubMed Central  Google Scholar 

  245. Nord, C. E., Rasmanis, G. & Wahlund, E. Effect of dalbavancin on the normal intestinal microflora. J. Antimicrob. Chemother. 58, 627–631 (2006).

    CAS  PubMed  Google Scholar 

  246. Ramdeen, S. & Boucher, H. W. Dalbavancin for the treatment of acute bacterial skin and skin structure infections. Expert Opin. Pharmacother. 16, 2073–2081 (2015).

    PubMed  PubMed Central  Google Scholar 

  247. Messina, J. A., Fowler, V. G. Jr & Corey, G. R. Oritavancin for acute bacterial skin and skin structure infections. Expert Opin. Pharmacother. 16, 1091–1098 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  248. Biedenbach, D. J., Arhin, F. F., Moeck, G., Lynch, T. F. & Sahm, D. F. In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011–2014. Int. J. Antimicrob. Agents 46, 674–681 (2015).

    CAS  PubMed  Google Scholar 

  249. Prokocimer, P., De Anda, C., Fang, E., Mehra, P. & Das, A. Tedizolid phosphate versus linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA 309, 559–569 (2013).

    CAS  PubMed  Google Scholar 

  250. Moran, G. J. et al. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect. Dis. 14, 696–705 (2014).

    CAS  PubMed  Google Scholar 

  251. Van Bambeke, F. Delafloxacin, a non-zwitterionic fluoroquinolone in Phase III of clinical development: evaluation of its pharmacology, pharmacokinetics, pharmacodynamics and clinical efficacy. Future Microbiol. 10, 1111–1123 (2015).

    CAS  PubMed  Google Scholar 

  252. Kingsley, J. et al. A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin. J. Antimicrob. Chemother 71, 821–829 (2016).

    CAS  PubMed  Google Scholar 

  253. Pullman, J. et al. Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: a phase 3, double-blind, randomized study. J. Antimicrob. Chemother. 72, 3471–3480 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

H.d.L. thanks A. Tomasz and C. Milheiriço for helpful discussions while preparing the manuscript. H.d.L.'s research is supported by Project LISBOA-01-0145-FEDER-007660 funded by the European Regional Development Fund through COMPETE2020 (POCI) and by national funds through Fundação para a Ciência e Tecnologia. A.P. thanks S. Heilbronner for helpful discussions and critical reading of the manuscript. A.P.'s research is supported by grants from the Deutsche Forschungsgemeinschaft (TRR34, TRR156, SFB766, SFB685, GRK1708 and PE805/5-1), the Deutsches Zentrum für Infektionsforschung (TTU HAARBI) and the European Innovative Medicines Initiative (COMBACTE). S.H. receives financial support from COMBACTE.

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Authors and Affiliations

  1. Departments of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

    Andie S. Lee

  2. Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia

    Andie S. Lee

  3. Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, NY, USA

    Hermínia de Lencastre

  4. Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal

    Hermínia de Lencastre

  5. Department of Medicine, Hospital Universitari Mutua de Terrassa, Barcelona, Spain

    Javier Garau

  6. Department of Infection Control, Amphia Hospital, Breda, Netherlands

    Jan Kluytmans

  7. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

    Jan Kluytmans

  8. Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Universiteit Antwerpen, Wilrijk, Belgium

    Surbhi Malhotra-Kumar

  9. Infection Biology Department, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany

    Andreas Peschel

  10. German Center for Infection Research, Partner Site Tübingen, Tübingen, Germany

    Andreas Peschel

  11. Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, WHO Collaborating Center, Geneva, Switzerland

    Stephan Harbarth

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Contributions

Introduction (A.S.L.); Epidemiology (A.S.L. and S.H.); Mechanisms/pathophysiology (H.d.L., S.M.-K., J.K. and A.P.); Diagnosis, screening and prevention (A.S.L., S.M.-K. and S.H.); Management (J.K., S.H. and J.G.); Quality of life (S.H.); Outlook (A.P. and S.H.); Overview of Primer (S.H. and A.S.L.).

Corresponding authors

Correspondence to Andie S. Lee or Stephan Harbarth.

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Competing interests

J.G. has acted as a consultant for Roche, Nabriva, Paratek and Menarini. J.K. acts as a consultant for Pfizer, 3M and Destiny Pharma. S.M.-K. has received grants from Abbott and Agfa Health. She is receiving research grants from Pfizer and Huvepharma and has a service agreement with AiCuris. A.P. receives a consultant fee from Crucell and research grants from Crucell, Medimmune, MorphoSys and Roche; he has a patent pending for lugdunin. S.H. was a temporary member of the speakers’ bureau for Takeda; has participated in the scientific advisory boards of DNA Electronics, Sandoz, GlaxoSmithKline and Bayer; and has received financial support for research activities from Pfizer and B. Braun. A.S.L. and H.d.L. declare no conflicts of interest.

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Lee, A., de Lencastre, H., Garau, J. et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers 4, 18033 (2018). https://doi.org/10.1038/nrdp.2018.33

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