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An Antibiotic Study Table Comparing VRE Drugs: Daptomycin, Linezolid, and Tigecycline

This text and table is intended for use as a study tool to assist people learning pharmacology of agents used for vancomycin-resistant enterococci (VRE) infections in the acute care setting. Basic information on VRE and a study table comparing VRE drugs daptomycin, linezolid, and tigecycline is provided.



Authored by: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID and Erin K. McCreary, Pharm.D., BCPS


[Last updated: 28 November 2017]

As infectious diseases pharmacists, we have seen many patients treated for vancomycin-resistant enterococci (VRE). Pulling from our training and experience, we have composed this article comparing daptomycin, linezolid, and tigecycline, with the intention of providing a resource for assisting trainees learning common antibiotic treatment options for VRE infection.

The information in this comparison includes some of the most common considerations to be aware of in clinical practice. Readers are cautioned that: (1) this is not a complete review of these three agents, (2) some of what is presented is based upon the opinion of the authors, and (3) this is not a replacement for sound clinical judgment. This is provided for study purposes only.

A little about Enterococci

Under a microscope enterococci look like Gram positive cocci in chains or pairs. They were once grouped with streptococci, but are currently considered their own unique genus of bacteria. Enterococci are facultatively anaerobic bacteria and are common colonizers of the gut. When identified from urine or respiratory cultures, they often represent contamination rather than infection. Infective endocarditis is one of the most serious infections caused by enterococci.

The two most common species of enterococci to cause human infection are Enterococcus faecalis and Enterococcus faecium. Aminopenicillins (e.g., ampicillin, amoxicillin) are widely considered the drugs of choice for infections caused by susceptible isolates, with vancomycin as a second-line drug. Both of these species can acquire vancomycin resistance through genes that cause peptidoglycan precursors to form that have decreased affinity for glycopeptide antibiotics like vancomycin. When vancomycin resistance is present, the organism is called a VRE. Approximately 80% of E. faecium and 5% of E. faecalis strains are vancomycin resistant [1]. Aminopenicillins can still be an option for ampicillin-sensitive VRE isolates.

For VRE infections that cannot be managed with an aminopenicillin, the antibiotics daptomycin, linezolid, and tigecycline are three of the most common therapeutic options to consider. There are other drugs that have activity in vitro against VRE (tedizolid, quinupristin/dalfopristin, fosfomycin, oritavancin, telavancin, chloramphenicol, and nitrofurantoin), however, these are used relatively infrequently for systemic VRE infection in the acute care setting.

Comparison of linezolid, daptomycin, and tigecycline

Linezolid Daptomycin Tigecycline
Brand name Zyvox Cubicin Tygacil
Generic available Yes Yes Yes
Year FDA-approved 2000 2003 2005
Mechanism of action // drug class Inhibition of protein synthesis via 23 rRNA of the 50S subunit

// Oxazolidinone

Cell membrane depolarization

// Cyclic lipopeptide

Inhibition of protein synthesis via 30S subunit

// Glycylcycline

Resistance in VRE possible Yes Yes Yes
Resistance mechanism Altered binding site Mutations controlling cell-envelope stress response Altered binding site
Available oral Yes No No
Available injectable Yes Yes Yes
Loading dose* No No Yes (100mg)
Usual dose* 600mg 4-12mg/kg** 50mg
Usual frequency* Q12H Q24H Q12H
Renal adjustment No Yes No
Hepatic adjustment No No Yes
FDA–approved indication for VRE infection Yes No No
FDA–approved indication for Staphyloccoccus aureus bacteremia No Yes

No

(Achieves poor serum concentrations)

FDA–approved indication for pneumonia Yes

No

(Inactivated by lung surfactant)

Yes
FDA–approved indication for intra-abdominal infection No No Yes
FDA–approved indication for skin/soft tissue infection Yes Yes Yes
FDA–approved indication for urinary tract infection No No No
MRSA activity Yes Yes Yes
VRE activity Yes Yes Yes
Gram-negative organism activity No No Yes
Pseudomonas aeurginosa activity No No No
Bacteroides fragilis activity (anaerobe) No No Yes
Mycobacterium spp. activity Yes No Yes
Notable toxicities to beware Peripheral neuropathy, optic neuritis, thrombocytopenia, serotonin syndrome CPK elevation, myopathy, eosinophilic pneumonitis Nausea, vomiting, diarrhea, LFT abnormalities
Typical baseline and weekly lab monitoring CBC, BMP CBC, CMP, CK CBC, CMP
FDA boxed warnings No No Yes
Major drug-drug interactions MAO inhibitors, SSRIs, SNRIs Monitor for myopathy closely in patients taking concomitant statins None

*Refers to adults

**Dose depends on organism. In general: 4 mg/kg for skin infection, 6mg/kg for Staphylococcal infection, 8mg/kg for Enterococcal infection. Up to 10-12mg/kg for high-MIC pathogens and/or VRE bacteremia has been studied. Commonly rounded to nearest 50mg.

Abbreviations: BMP = basic metabolic panel; CBC = complete blood count; CMP = comprehensive metabolic panel; CK = creatinine kinase; CPK = creatinine phosphokinase; FDA = Food and Drug Administration; LFT = Liver Function Test; MAO = monoamine oxidase; MRSA = methicillin-sensitive Staphylococcus aureus; SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin/ norepinephrine reuptake inhibitor; VRE = vancomycin-resistant enterococci

Closing comments

When it comes to infections caused by Gram-positive bacteria, VRE are feared by many clinicians. In fact, VRE are so problematic that it was labeled a serious threat to human health by the United States Centers for Disease Control and Prevention in 2013. Unfortunately, it looks like VRE will be a problem for healthcare providers for many years to come yet.

We hope this study table can help serve as a resource for people seeking to learn basic pharmacology information of these three antibiotics used to treat VRE infection in the acute care setting.

Recommended Readings

1. Mandell, Douglas, and Bennet’s Principals and Practice of Infectious Diseases, eighth edition. Chapter 30 and chapter 202. 

2. Arias CA, Murray EB. The Rise of Enterococcus: Beyond Vancomycin Resistance. Nature Reviews Microbiology. 2012.

3. Murray EB. The Life and Times of Enterococcus. Clinical Microbiology Reviews. 1990.

4. Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence. Pharmacotherapy. 2017.

5. Vancomycin-resistant enterococcal bacteremia pharmacotherapy. Annals of Pharmacotherapy. 2015.

6. Treatment considerations in vancomycin-resistant enterococcal bacteremia: daptomycin or linezolid? A review. International Journal of Clinical Pharmacy. 2013.

Disclosures: The authors report no financial conflicts of interest.


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Filed Under: Infectious Diseases & Antimicrobial Stewardship

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