Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections

doi:10.1128/cmr.00059-22

Review

. 2023 Jun 21;36(2):e0005922.

doi: 10.1128/cmr.00059-22. Epub 2023 Apr 17.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections

Kelly A Cairns^{1

2}, Andrew A Udy^{3

4}, Trisha N Peel¹, Iain J Abbott^{1

5}, Michael J Dooley^{2

6}, Anton Y Peleg^{1

7

8}

Affiliations

¹ Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
² Pharmacy Department, Alfred Health, Melbourne, Victoria, Australia.
³ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁴ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, Victoria, Australia.
⁵ Microbiology Unit, Alfred Health, Melbourne, Victoria, Australia.
⁶ Centre for Medicines Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
⁷ Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia.
⁸ Centre to Impact AMR, Monash University, Clayton, Victoria, Australia.

PMID: 37067406
PMCID: PMC10283489
DOI: 10.1128/cmr.00059-22

Review

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections

Kelly A Cairns et al. Clin Microbiol Rev. 2023.

. 2023 Jun 21;36(2):e0005922.

doi: 10.1128/cmr.00059-22. Epub 2023 Apr 17.

Authors

Kelly A Cairns^{1

2}, Andrew A Udy^{3

4}, Trisha N Peel¹, Iain J Abbott^{1

5}, Michael J Dooley^{2

6}, Anton Y Peleg^{1

7

8}

Affiliations

¹ Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
² Pharmacy Department, Alfred Health, Melbourne, Victoria, Australia.
³ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁴ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, Victoria, Australia.
⁵ Microbiology Unit, Alfred Health, Melbourne, Victoria, Australia.
⁶ Centre for Medicines Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
⁷ Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia.
⁸ Centre to Impact AMR, Monash University, Clayton, Victoria, Australia.

PMID: 37067406
PMCID: PMC10283489
DOI: 10.1128/cmr.00059-22

Abstract

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Keywords: VRE; bacteremia; daptomycin; linezolid; teicoplanin; therapeutic drug monitoring.

PubMed Disclaimer

Conflict of interest statement

The authors declare a conflict of interest. This research received no specific financial support. I.J.A. has undertaken advisory board consultancy for Merck Sharp & Dohme (Australia; June 2021); A.Y.P. has received an investigator-initiated research grant from Merck Sharp & Dohme unrelated to the current project.

Figures

**FIG 1**
Role of VRE in colonization and infection.

See this image and copyright information in PMC

Cited by

Natural flavonoids combat cytosolic MRSA by potentiating phagosome acidification.
Si X, Lv R, Cai Z, Sun Z, Zhang W, Wang J, Liu X. Si X, et al. Cell Commun Signal. 2025 Jun 2;23(1):259. doi: 10.1186/s12964-025-02252-6. Cell Commun Signal. 2025. PMID: 40457373 Free PMC article.
Risk Factors for 30-Day Mortality in Nosocomial Enterococcal Bloodstream Infections.
Zerbato V, Pol R, Sanson G, Suru DA, Pin E, Tabolli V, Monticelli J, Busetti M, Toc DA, Crocè LS, Luzzati R, Di Bella S. Zerbato V, et al. Antibiotics (Basel). 2024 Jun 27;13(7):601. doi: 10.3390/antibiotics13070601. Antibiotics (Basel). 2024. PMID: 39061283 Free PMC article.
Probiotics and Their Bioproducts: A Promising Approach for Targeting Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus.
Jain M, Stitt G, Son L, Enioutina EY. Jain M, et al. Microorganisms. 2023 Sep 25;11(10):2393. doi: 10.3390/microorganisms11102393. Microorganisms. 2023. PMID: 37894051 Free PMC article. Review.
Antimicrobial and antibiofilm effects of essential fatty acids against clinically isolated vancomycin-resistant Enterococcus faecium.
Wei M, Wang P, Li T, Wang Q, Su M, Gu L, Wang S. Wei M, et al. Front Cell Infect Microbiol. 2023 Sep 29;13:1266674. doi: 10.3389/fcimb.2023.1266674. eCollection 2023. Front Cell Infect Microbiol. 2023. PMID: 37842001 Free PMC article.
The Evolving Landscape of Infective Endocarditis: Difficult-to-Treat Resistance Bacteria and Novel Diagnostics at the Foreground.
Rapti V, Giannitsioti E, Spernovasilis N, Magiorakos AP, Poulakou G. Rapti V, et al. J Clin Med. 2025 Mar 19;14(6):2087. doi: 10.3390/jcm14062087. J Clin Med. 2025. PMID: 40142895 Free PMC article. Review.

See all "Cited by" articles

References

1. Dalton KR, Rock C, Carroll KC, Davis MF. 2020. One Health in hospitals: how understanding the dynamics of people, animals, and the hospital built-environment can be used to better inform interventions for antimicrobial-resistant Gram-positive infections. Antimicrob Resist Infect Control 9:78. doi:10.1186/s13756-020-00737-2. - DOI - PMC - PubMed
1. Australian Government. 2015. Responding to the threat of antimicrobial resistance, Australia’s first national antimicrobial resistance strategy 2015–2019. Commonwealth of Australia, Canberra, ACT, Australia.
1. CDC. 2019. Antibiotic resistance threats in the United States, 2019. US Department of Health and Human Services, CDC, Atlanta, GA. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-re....
1. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N. WHO Pathogens Priority List Working Group. 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318–327. doi:10.1016/S1473-3099(17)30753-3. - DOI - PubMed
1. Founou RC, Blocker AJ, Noubom M, Tsayem C, Choukem SP, Van Dongen M, Founou LL. 2021. The COVID-19 pandemic: a threat to antimicrobial resistance containment. Future Sci OA 7:FSO736. doi:10.2144/fsoa-2021-0012. - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

[1] Dalton KR, Rock C, Carroll KC, Davis MF. 2020. One Health in hospitals: how understanding the dynamics of people, animals, and the hospital built-environment can be used to better inform interventions for antimicrobial-resistant Gram-positive infections. Antimicrob Resist Infect Control 9:78. doi:10.1186/s13756-020-00737-2. - DOI - PMC - PubMed

[2] Dalton KR, Rock C, Carroll KC, Davis MF. 2020. One Health in hospitals: how understanding the dynamics of people, animals, and the hospital built-environment can be used to better inform interventions for antimicrobial-resistant Gram-positive infections. Antimicrob Resist Infect Control 9:78. doi:10.1186/s13756-020-00737-2. - DOI - PMC - PubMed

[3] Australian Government. 2015. Responding to the threat of antimicrobial resistance, Australia’s first national antimicrobial resistance strategy 2015–2019. Commonwealth of Australia, Canberra, ACT, Australia.

[4] Australian Government. 2015. Responding to the threat of antimicrobial resistance, Australia’s first national antimicrobial resistance strategy 2015–2019. Commonwealth of Australia, Canberra, ACT, Australia.

[5] CDC. 2019. Antibiotic resistance threats in the United States, 2019. US Department of Health and Human Services, CDC, Atlanta, GA. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-re....

[6] CDC. 2019. Antibiotic resistance threats in the United States, 2019. US Department of Health and Human Services, CDC, Atlanta, GA. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-re....

[7] Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N. WHO Pathogens Priority List Working Group. 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318–327. doi:10.1016/S1473-3099(17)30753-3. - DOI - PubMed

[8] Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N. WHO Pathogens Priority List Working Group. 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318–327. doi:10.1016/S1473-3099(17)30753-3. - DOI - PubMed

[9] Founou RC, Blocker AJ, Noubom M, Tsayem C, Choukem SP, Van Dongen M, Founou LL. 2021. The COVID-19 pandemic: a threat to antimicrobial resistance containment. Future Sci OA 7:FSO736. doi:10.2144/fsoa-2021-0012. - DOI - PMC - PubMed

[10] Founou RC, Blocker AJ, Noubom M, Tsayem C, Choukem SP, Van Dongen M, Founou LL. 2021. The COVID-19 pandemic: a threat to antimicrobial resistance containment. Future Sci OA 7:FSO736. doi:10.2144/fsoa-2021-0012. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections

Affiliations

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical