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
3. Murray EB. The Life and Times of Enterococcus. Clinical Microbiology Reviews. 1990.
5. Vancomycin-resistant enterococcal bacteremia pharmacotherapy. Annals of Pharmacotherapy. 2015.
Disclosures: The authors report no financial conflicts of interest.
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