UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus infections

Author
Franklin D Lowy, MD
Section Editor
Daniel J Sexton, MD
Deputy Editor
Elinor L Baron, MD, DTMH

INTRODUCTION

The emergence of Staphylococcus aureus with diminished vancomycin susceptibility was anticipated when vancomycin-resistant enterococci (VRE) were initially described in the late 1980s [1,2]. The expected mechanism of vancomycin resistance in S. aureus was plasmid-mediated transfer of the vanA gene cluster from VRE. It was a surprise, therefore, when the first reported case of diminished vancomycin susceptibility in a clinical isolate of S. aureus in 1997 was mediated not via acquisition of vanA by a strain of methicillin-resistant S. aureus (MRSA) but by an unusually thickened cell wall containing dipeptides capable of binding vancomycin, thereby reducing availability of the drug for intracellular target molecules [3-8]. This was the first observation of vancomycin-intermediate S. aureus (VISA). The predicted mechanism of vanA gene plasmid-mediated transfer from enterococci to S. aureus was later observed for the first time in 2002; this was the first description of vancomycin-resistant S. aureus (VRSA) [9,10].

Issues related to the mechanism, epidemiology, laboratory definitions, treatment, and prevention of S. aureus with reduced susceptibility to vancomycin will be reviewed here. Issues related to MRSA are discussed separately. (See related topics.)

DEFINITIONS

Both the Clinical and Laboratory Standards Institute (CLSI) and the United States Food and Drug Administration (FDA) have established the following vancomycin minimum inhibitory concentration (MIC) interpretive criteria for S. aureus. The definitions have been modified in response to increasing reports of vancomycin treatment failure in infections due to strains with elevated MICs (2 mcg/mL), as well as to flag those isolates that are likely to be heteroresistant; the definitions prior to 2006 are noted in parentheses [11-13]. (See 'Heteroresistance' below.)

Vancomycin susceptible – ≤2 mcg/mL (≤4 mcg/mL)

Vancomycin intermediate – 4 to 8 mcg/mL (8 to 16 mcg/mL)

              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Oct 01 00:00:00 GMT 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med 1988; 319:157.
  2. Uttley AH, Collins CH, Naidoo J, George RC. Vancomycin-resistant enterococci. Lancet 1988; 1:57.
  3. Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997; 40:135.
  4. Cui L, Ma X, Sato K, et al. Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. J Clin Microbiol 2003; 41:5.
  5. Sieradzki K, Tomasz A. Gradual alterations in cell wall structure and metabolism in vancomycin-resistant mutants of Staphylococcus aureus. J Bacteriol 1999; 181:7566.
  6. Cui L, Iwamoto A, Lian JQ, et al. Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 2006; 50:428.
  7. Hanaki H, Kuwahara-Arai K, Boyle-Vavra S, et al. Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50. J Antimicrob Chemother 1998; 42:199.
  8. Cui L, Murakami H, Kuwahara-Arai K, et al. Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Antimicrob Agents Chemother 2000; 44:2276.
  9. Centers for Disease Control and Prevention (CDC). Staphylococcus aureus resistant to vancomycin--United States, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:565.
  10. Howden BP, Davies JK, Johnson PD, et al. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev 2010; 23:99.
  11. Soriano A, Marco F, Martínez JA, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008; 46:193.
  12. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Sixteenth Informational Supplement. M100-S16 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved Standard. Vol 26. No 3. CLSI, Wayne, PA 2006.
  13. Tenover FC, Moellering RC Jr. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clin Infect Dis 2007; 44:1208.
  14. Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 2004; 42:2398.
  15. Hussain FM, Boyle-Vavra S, Shete PB, Daum RS. Evidence for a continuum of decreased vancomycin susceptibility in unselected Staphylococcus aureus clinical isolates. J Infect Dis 2002; 186:661.
  16. Song JH, Hiramatsu K, Suh JY, et al. Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin. Antimicrob Agents Chemother 2004; 48:4926.
  17. Pillai SK, Wennersten C, Venkataraman L, et al. Development of reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus. Clin Infect Dis 2009; 49:1169.
  18. Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339:520.
  19. Howden BP, Johnson PD, Ward PB, et al. Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2006; 50:3039.
  20. Walsh TR, Howe RA. The prevalence and mechanisms of vancomycin resistance in Staphylococcus aureus. Annu Rev Microbiol 2002; 56:657.
  21. Mwangi MM, Wu SW, Zhou Y, et al. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. Proc Natl Acad Sci U S A 2007; 104:9451.
  22. Howden BP, Stinear TP, Allen DL, et al. Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52:3755.
  23. Howden BP, McEvoy CR, Allen DL, et al. Evolution of multidrug resistance during Staphylococcus aureus infection involves mutation of the essential two component regulator WalKR. PLoS Pathog 2011; 7:e1002359.
  24. Shoji M, Cui L, Iizuka R, et al. walK and clpP mutations confer reduced vancomycin susceptibility in Staphylococcus aureus. Antimicrob Agents Chemother 2011; 55:3870.
  25. Sakoulas G, Eliopoulos GM, Moellering RC Jr, et al. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob Agents Chemother 2002; 46:1492.
  26. Smith TL, Pearson ML, Wilcox KR, et al. Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group. N Engl J Med 1999; 340:493.
  27. Rotun SS, McMath V, Schoonmaker DJ, et al. Staphylococcus aureus with reduced susceptibility to vancomycin isolated from a patient with fatal bacteremia. Emerg Infect Dis 1999; 5:147.
  28. Sieradzki K, Roberts RB, Haber SW, Tomasz A. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 1999; 340:517.
  29. Centers for Disease Control and Prevention (CDC). Staphylococcus aureus with reduced susceptibility to vancomycin--Illinois, 1999. MMWR Morb Mortal Wkly Rep 2000; 48:1165.
  30. Centers for Disease Control and Prevention (CDC). Update: Staphylococcus aureus with reduced susceptibility to vancomycin--United States, 1997. MMWR Morb Mortal Wkly Rep 1997; 46:813.
  31. Hiramatsu K, Aritaka N, Hanaki H, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 1997; 350:1670.
  32. Fridkin SK. Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clin Infect Dis 2001; 32:108.
  33. Ploy MC, Grélaud C, Martin C, et al. First clinical isolate of vancomycin-intermediate Staphylococcus aureus in a French hospital. Lancet 1998; 351:1212.
  34. Oliveira GA, Dell'Aquila AM, Masiero RL, et al. Isolation in Brazil of nosocomial Staphylococcus aureus with reduced susceptibility to vancomycin. Infect Control Hosp Epidemiol 2001; 22:443.
  35. Kim MN, Pai CH, Woo JH, et al. Vancomycin-intermediate Staphylococcus aureus in Korea. J Clin Microbiol 2000; 38:3879.
  36. Holland TL, Fowler VG Jr. Vancomycin minimum inhibitory concentration and outcome in patients with Staphylococcus aureus bacteremia: pearl or pellet? J Infect Dis 2011; 204:329.
  37. Holmes NE, Turnidge JD, Munckhof WJ, et al. Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations. J Infect Dis 2011; 204:340.
  38. Hubert SK, Mohammed JM, Fridkin SK, et al. Glycopeptide-intermediate Staphylococcus aureus: evaluation of a novel screening method and results of a survey of selected U.S. hospitals. J Clin Microbiol 1999; 37:3590.
  39. Wong SS, Ho PL, Woo PC, Yuen KY. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance. Clin Infect Dis 1999; 29:760.
  40. Deresinski S. Vancomycin heteroresistance and methicillin-resistant Staphylococcus aureus. J Infect Dis 2009; 199:605.
  41. Charles PG, Ward PB, Johnson PD, et al. Clinical features associated with bacteremia due to heterogeneous vancomycin-intermediate Staphylococcus aureus. Clin Infect Dis 2004; 38:448.
  42. Bae IG, Federspiel JJ, Miró JM, et al. Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance. J Infect Dis 2009; 200:1355.
  43. Wootton M, Howe RA, Hillman R, et al. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. J Antimicrob Chemother 2001; 47:399.
  44. Noble WC, Virani Z, Cree RG. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992; 72:195.
  45. Clark NC, Weigel LM, Patel JB, Tenover FC. Comparison of Tn1546-like elements in vancomycin-resistant Staphylococcus aureus isolates from Michigan and Pennsylvania. Antimicrob Agents Chemother 2005; 49:470.
  46. Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis 2006; 42 Suppl 1:S25.
  47. Kos VN, Desjardins CA, Griggs A, et al. Comparative genomics of vancomycin-resistant Staphylococcus aureus strains and their positions within the clade most commonly associated with Methicillin-resistant S. aureus hospital-acquired infection in the United States. MBio 2012; 3.
  48. Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med 2003; 348:1342.
  49. Centers for Disease Control and Prevention (CDC). Vancomycin-resistant Staphylococcus aureus--Pennsylvania, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:902.
  50. Tenover FC, Weigel LM, Appelbaum PC, et al. Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania. Antimicrob Agents Chemother 2004; 48:275.
  51. Whitener CJ, Park SY, Browne FA, et al. Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clin Infect Dis 2004; 38:1049.
  52. Centers for Disease Control and Prevention (CDC). Vancomycin-resistant Staphylococcus aureus--New York, 2004. MMWR Morb Mortal Wkly Rep 2004; 53:322.
  53. Sievert DM, Rudrik JT, Patel JB, et al. Vancomycin-resistant Staphylococcus aureus in the United States, 2002-2006. Clin Infect Dis 2008; 46:668.
  54. Limbago BM, Kallen AJ, Zhu W, et al. Report of the 13th vancomycin-resistant Staphylococcus aureus isolate from the United States. J Clin Microbiol 2014; 52:998.
  55. Walters MS, Eggers P, Albrecht V, et al. Vancomycin-Resistant Staphylococcus aureus - Delaware, 2015. MMWR Morb Mortal Wkly Rep 2015; 64:1056.
  56. Melo-Cristino J, Resina C, Manuel V, et al. First case of infection with vancomycin-resistant Staphylococcus aureus in Europe. Lancet 2013; 382:205.
  57. Rossi F, Diaz L, Wollam A, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med 2014; 370:1524.
  58. Furuno JP, Perencevich EN, Johnson JA, et al. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci co-colonization. Emerg Infect Dis 2005; 11:1539.
  59. Tenover FC. Vancomycin-resistant Staphylococcus aureus: a perfect but geographically limited storm? Clin Infect Dis 2008; 46:675.
  60. Mendes RE, Deshpande LM, Castanheira M, et al. First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob Agents Chemother 2008; 52:2244.
  61. Sánchez García M, De la Torre MA, Morales G, et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA 2010; 303:2260.
  62. Bonilla H, Huband MD, Seidel J, et al. Multicity outbreak of linezolid-resistant Staphylococcus epidermidis associated with clonal spread of a cfr-containing strain. Clin Infect Dis 2010; 51:796.
  63. Swenson JM, Anderson KF, Lonsway DR, et al. Accuracy of commercial and reference susceptibility testing methods for detecting vancomycin-intermediate Staphylococcus aureus. J Clin Microbiol 2009; 47:2013.
  64. Centers for Disease Control and Prevention (CDC). Laboratory capacity to detect antimicrobial resistance, 1998. MMWR Morb Mortal Wkly Rep 2000; 48:1167.
  65. Tenover FC, Lancaster MV, Hill BC, et al. Characterization of staphylococci with reduced susceptibilities to vancomycin and other glycopeptides. J Clin Microbiol 1998; 36:1020.
  66. Tenover FC, Biddle JW, Lancaster MV. Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerg Infect Dis 2001; 7:327.
  67. Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis 2004; 39:539.
  68. Centers for Disease Control and Prevention: Healthcare-associated Infections (HAI) http://www.cdc.gov/ncidod/dhqp/ar_visavrsa_algo.html (Accessed on August 20, 2009).
  69. Liu C, Bayer A, Cosgrove SE, 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 2011; 52:e18.
  70. Lodise TP, Graves J, Evans A, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother 2008; 52:3315.
  71. Chang FY, Peacock JE Jr, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003; 82:333.
  72. van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis 2012; 54:755.
  73. Kalil AC, Van Schooneveld TC, Fey PD, Rupp ME. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis. JAMA 2014; 312:1552.
  74. Deresinski S. Counterpoint: Vancomycin and Staphylococcus aureus--an antibiotic enters obsolescence. Clin Infect Dis 2007; 44:1543.
  75. Choice of antibacterial drugs. Treat Guidel Med Lett 2007; 5:33.
  76. Drew RH, Perfect JR, Srinath L, et al. Treatment of methicillin-resistant staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. For the Synercid Emergency-Use Study Group. J Antimicrob Chemother 2000; 46:775.
  77. Moise PA, Forrest A, Birmingham MC, Schentag JJ. The efficacy and safety of linezolid as treatment for Staphylococcus aureus infections in compassionate use patients who are intolerant of, or who have failed to respond to, vancomycin. J Antimicrob Chemother 2002; 50:1017.
  78. Cha R, Brown WJ, Rybak MJ. Bactericidal activities of daptomycin, quinupristin-dalfopristin, and linezolid against vancomycin-resistant Staphylococcus aureus in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2003; 47:3960.
  79. Saravolatz LD, Pawlak J, Johnson LB. In vitro susceptibilities and molecular analysis of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus isolates. Clin Infect Dis 2012; 55:582.
  80. Boucher HW, Sakoulas G. Perspectives on Daptomycin resistance, with emphasis on resistance in Staphylococcus aureus. Clin Infect Dis 2007; 45:601.
  81. Hidayat LK, Hsu DI, Quist R, et al. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 2006; 166:2138.
  82. Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991; 115:674.
  83. Deresinski S. Vancomycin in combination with other antibiotics for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2009; 49:1072.
  84. Fowler VG Jr, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006; 355:653.
  85. Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis 2011; 53:158.
  86. Fridkin SK, Hageman J, McDougal LK, et al. Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997-2001. Clin Infect Dis 2003; 36:429.
  87. Jevitt LA, Smith AJ, Williams PP, et al. In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Microb Drug Resist 2003; 9:389.
  88. Climo MW, Patron RL, Archer GL. Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin. Antimicrob Agents Chemother 1999; 43:1747.
  89. Howe RA, Wootton M, Bennett PM, et al. Interactions between methicillin and vancomycin in methicillin-resistant Staphylococcus aureus strains displaying different phenotypes of vancomycin susceptibility. J Clin Microbiol 1999; 37:3068.
  90. de Lassence A, Hidri N, Timsit JF, et al. Control and outcome of a large outbreak of colonization and infection with glycopeptide-intermediate Staphylococcus aureus in an intensive care unit. Clin Infect Dis 2006; 42:170.
  91. Wenzel RP, Edmond MB. Vancomycin-resistant Staphylococcus aureus: infection control considerations. Clin Infect Dis 1998; 27:245.
  92. Evans ME, Kortas KJ. Vancomycin use in a university medical center: comparison with hospital infection control practices advisory committee guidelines. Infect Control Hosp Epidemiol 1996; 17:356.