Skip to main content
Log in

Treatment of Vancomycin-Resistant Enterococci: Focus on Daptomycin

  • Antimicrobial Development and Drug Resistance (A Pakyz, Section Editors)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Vancomycin-resistant Enterococci (VRE) infections are problematic due to limited availability of anti-VRE agents and their potential for adverse effects and drug interactions. This review focuses on the role of daptomycin in treating VRE infections by summarizing key points of relevant clinical studies.

Recent Findings

Higher doses of daptomycin (≥ 6 mg/kg), as compared to standard doses, were found to be safe in terms of creatinine phosphokinase elevation and associated with successful infection outcomes and microbiological clearance. High doses are especially important in treatment of infections involving elevated daptomycin minimum inhibitory concentration (MIC) values (3–4 μg/mL).

Summary

Daptomycin, especially in higher doses, has been shown to be an effective and safe VRE agent for a variety of serious infection types, such as catheter-associated bloodstream and intra-abdominal infections, and for different populations including oncology. Infections involving higher daptomycin MIC values were associated with previous daptomycin use and prosthetic devices.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med. 1988;319:157–61.

    Article  CAS  PubMed  Google Scholar 

  2. The Centers for Disease Control and Prevention. Antibiotic resistant threats in the United States, 2013. Available at: https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.

  3. Weiner LM, Webb AK, Limbago R, Dudeck MA, Patel J, Kallen AJ, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol. 2016;37:1288–301.

    Article  PubMed  Google Scholar 

  4. Department of Health and Human Services. Supplement Approval Synercid I.V. (quinupristin and dalfoprisitn for infection). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/050747s011,050748s009,050748s010ltr.pdf. Accessed July 05, 2017.

  5. Carver PL, Whang E, VandenBussche HL, Kauffman CA, Malani PN. Risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin therapy. Pharmacotherapy. 2003;23:159–64.

    Article  CAS  PubMed  Google Scholar 

  6. Zyvox [package insert]. New York, NY: Pharmacia & Upjohn Company; 2015.

  7. Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ. Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program. Clin Infect Dis. 2003;36:159–68.

    Article  CAS  PubMed  Google Scholar 

  8. Matsumoto K, Takeshita A, Ikawa K, Shigemi A, Yaji K, Shimodozono Y, et al. Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction. Int J Antimicrob Agents. 2010;36:179–81.

    Article  CAS  PubMed  Google Scholar 

  9. Hogan HL, Hachem RY, Neuhauser M, Raad II, Coyle E. Clinical experience of linezolid in bone marrow transplantation patients. J Pharm Pract. 2010;23:352–7.

    Article  PubMed  Google Scholar 

  10. Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007;27:1189–97.

    Article  CAS  PubMed  Google Scholar 

  11. Mendes RE, Deshpande LM, Jones RN. Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat. 2014;17:1–12.

    Article  PubMed  Google Scholar 

  12. McGregor JC, Hartung DM, Allen GP, Taplitz RA, Traver R, Tong T, et al. Risk factors associated with linezolid non-susceptible enterococcal infections. Am J Infect Control. 2012;40:886–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cubicin [package insert]. Whitehouse Station, NJ: Merck & Co.; 2015.

  14. Balli EP, Venetis CA, Miyakis S. Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia. Antimicrob Agents Chemother. 2014;58:734–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chuang YC, Want JT, Lin HY, Chang SC. Daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bacteremia: systematic review and meta-analysis. BMC Infect Dis. 2014;14:687.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sader HS, Farrell DJ, Flamm RK, Jones RN. Daptomycin activity tested against 164 457 isolates from hospitalized patients: summary of 8 years of a Worldwide Surveillance Programme (2005–2012). Int J Antimicrob Agents. 2014;43:465–9.

    Article  CAS  PubMed  Google Scholar 

  17. •• Shukla BS, Shelbume S, Reyes K, et al. Influence of minimum inhibitory concentration of outcomes of Enterococcus faecium bacteremia treated with daptomycin: is it time to change the breakpoint? Clin Infect Dis. 2016;62:1514–20. This was a multicenter retrospective cohort from 2010 to 2015. Key findings were that elevated enterococcal MICs of 3 to 4 μg/mL and immunosuppression were associated with microbiologic failure to daptomycin.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tran TT, Munita JM, Arias CA. Mechanisms of drug resistance: daptomycin resistance. Ann N Y Acad Sci. 2015;1354:32–53.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Munita JM, Panesso D, Diaz L, et al. Correlation between mutations in liaFSR of Enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints. Antimicrob Agents and Chemother. 2012;56:4354–9.

    Article  CAS  Google Scholar 

  20. DiPippo AJ, Tverdek FP, Tarrand JJ, et al. Daptomycin non-susceptible Enterococcus faecium in leukemia patients: role of prior daptomycin exposure. J Inf Secur. 2017;74:243–7.

    Google Scholar 

  21. • Casapao AM, Kullar R, Davis SL, et al. Multicenter study of high-dose daptomycin for treatment of enterococcal infections. Antimicrob Agents Chemother. 2013;57:4190–6. This was a multicenter retrospective cohort of adult patients with serious enterococcal infections from 2005 to 2012. Important to this review, this was one of the first studies to document the clinical success of high doses of DAP compared to standard doses in terms of 30-day mortality.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. •• Britt NS, Potter EM, Patel N, Steed ME. Comparative effectiveness and safety of standard, medium-, and high-dose daptomycin strategies for the treatment of vancomycin-resistant enterococcal bacteremia among Veterans Affairs patients. Clin Infect Dis. 2017;64:605–13. This was a large-scale and high-quality multicenter retrospective cohort that compared standard, intermediate, and high doses of daptomycin. The study found that high doses improved 30-day mortality and microbiological clearance.

    PubMed  Google Scholar 

  23. • Chuang YC, Lin HY, Chen PY, et al. Effect of daptomycin dose on the outcome of vancomycin-resistant, daptomycin-susceptible Enterococcus faecium bacteremia. Clin Infect Dis. 2017;64:1026–34. This was a prospective observational cohort in two teaching hospitals in Taiwan. High doses of DAP showed improved 14-day mortality and microbiological clearance over lower doses.

    Article  PubMed  Google Scholar 

  24. Zasowski EJ, Claeys KC, Lagnf AM, Davis SL, Rybak MJ. Time is of the essence: the impact of delayed antibiotic therapy on patient outcomes in hospital-onset enterococcal bloodstream infections. Clin Infect Dis. 2016;62:1242–50.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Prematunge C, MacDougall C, Johnstone J, et al. VRE and VSE bacteremia outcomes in the era of effective therapy: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2016;37:26–35.

    Article  PubMed  Google Scholar 

  26. Chong PP, van Duin D, Bangdiwala A, et al. Vancomycin-resistant enterococcal bloodstream infections in hematopoietic stem cell transplant recipients and patients with hematologic malignancies: impact of daptomycin MICs of 3 to 4 mg/L. Clin Ther. 2016;38:2468–76.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amy L. Pakyz.

Ethics declarations

Conflict of Interest

Rose M. Kohinke and Dr. Amy Pakyz declare no relevant financial relationships.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

Additional information

This article is part of the Topical Collection on Antimicrobial Development and Drug Resistance

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kohinke, R.M., Pakyz, A.L. Treatment of Vancomycin-Resistant Enterococci: Focus on Daptomycin. Curr Infect Dis Rep 19, 33 (2017). https://doi.org/10.1007/s11908-017-0589-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11908-017-0589-2

Keywords

Navigation