Linezolid (Zyvox®) versus Vancomycin (Vancocin®)
Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch
Difference between Linezolid and Vancomycin
The first major difference between linezolid and vancomycin is their oral bioavailability. Only linezolid can be administered orally, whereas vancomycin is limited to parenteral use. Oral vancomycin is virtually not absorbed or metabolized, and is excreted in the stool unchanged. So this antibiotic is ideal for the treatment of Clostridium difficile infection.
The high bioavailability (close to 100%) of linezolid translates to reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost.
Linezolid may be particularly useful as an alternative to vancomycin in patients who have impaired renal function 11, poor intravenous access, require outpatient therapy, or who don't tolerate glycopeptides.
| Linezolid | Vancomycin | |
|---|---|---|
| Drug class | Antibiotic, Oxazolidinone |
Antibiotic, Glycopeptide |
| Preparations | Tablets, suspension, injection | Injection, capsules |
| Indications | • Vancomycin-Resistant Enterococcus faecium infections • Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), or Streptococcus pneumoniae (including multi-drug resistant strains). • Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible and resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae • Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible only) or Streptococcus pyogenes. • Community-acquired pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains) |
• Serious or severe infections caused by Gram-positive pathogens, especially those caused by methicillin-resistant staphylococci and in patients hypersensitive to β-lactam antibiotics • Endocarditis caused by Gram-positive pathogens Oral: • Enterocolitis caused by Staphylococcus aureus • Antibiotic-associated pseudomembranous due to C. difficile |
| Mechanism of action | Mainly bacteriostatic Linezolid inhibits bacterial protein synthesis by binding to a site on the bacterial ribosomal RNA of the 50S subunit and preventing the formation of the ternary complex at 70S ribosomal subunit. |
Mainly bactericidal Vancomycin inhibits the second stage of cell wall synthesis by preventing the transglycosylation step in polymerization of peptidoglycan (the major structural cell wall polymer). This weakens bacterial cell wall and damages the underlying cell membrane. |
| Spectrum of antimicrobial activity | • Enterococcus faecium (including vancomycin-resistant strains) • Enterococcus faecalis (including vancomycin-resistant strains) • Streptococcus pneumoniae (including multi-drug resistant isolates) • Staphylococcus haemolyticus • Pasteurella multocida |
• Diphtheroids • Enterococci • Streptococcus bovis • Listeria monocytogenes • Streptococcus pneumoniae (including penicillin- resistant strains) • Actinomyces species • Lactobacillus species • Clostridium difficile • Propionibacterium acnes |
| • Staphylococcus aureus (including methicillin-resistant strains) • Staphylococcus epidermidis (including methicillin-resistant strains) • Viridans group streptococci • Streptococcus pyogenes • Streptococcus agalactiae |
||
| Resistant bacteria | • Escherichia coli • Klebsiella pneumoniae • Pseudomonas aeruginosa All enterobacteria, and non-fermentative aerobic Gram-negative bacilli are resistant |
• Mycobacteria |
| Half-life | 4-6 hours | 4-6 hours (renal impairment will prolong the half-life) |
| Bioavailability | 100% | < 5% |
| Protein binding | 31% | 55% |
| Metabolism, Excretion |
• Linezolid is primarily metabolized by oxidation of the morpholine ring to two inactive metabolites, an aminoethoxyacetic acid (metabolite A) and a hydroxyethyl glycine (metabolite B). • 30% is eliminated in the urine as unchanged drug. Non renal clearance about 65%. |
• Vancomycin is not metabolized. • 80-90% is eliminated in the urine. Oral dose is excreted by feces. |
| Contraindications | • Hypersensitivity to linezolid • Monoamine Oxidase Inhibitors • Patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis • Patients taking sympathomimetic agents, vasopressive agents, dopaminergic agents |
• Hypersensitivity to vancomycin |
| Side effects, toxicity | • Compared with other antibacterials, linezolid is associated with a greater frequency of side effects, mainly nausea, vomiting, diarrhea and headaches. • Thrombocytopenia also occurs more frequently in patients taking linezolid but there is no increased frequency of anemia. • Myelosuppression • Peripheral and optic neuropathy are associated with long duration of treatment (3-6 months). |
• Ototoxicity • Nephrotoxicity. Concomitant use of aminoglycosides, preexisting kidney increase the risk of renal toxicity |
| Pregnancy category | C | |
| Advantages | • Excellent tissue penetration • Active against nearly all resistant gram-positive bacteria |
• Clean safety profile |
Pneumonia
The available evidence suggests that linezolid is at least as effective as vancomycin for the treatment nosocomial pneumonia. Several recent studies have confirmed linezolid superiority in comparison with vancomycin for Methicillin-resistant S. aureus (MRSA) nosocomial pneumonia, including ventilator-associated pneumonia (VAP) 10, elderly patients1.
Studies comparing vancomycin with linezolid in the treatment of MRSA pneumonia showed a significantly better survival rates with linezolid as compared to vancomycin3. Lung penetration advantages of linezolid over vancomycin are likely to be the reason.
| Results of multicenter, retrospective, observational study compared clinical success of linezolid versus vancomycin for MRSA VAP 10 | Linezolid | Vancomycin |
|---|---|---|
| Clinical success rate | 85% |
69% |
| Conclusion: Linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients. | ||
| Results of randomized comparison of linezolid and vancomycin for MRSA pneumonia (ZEPHyR Study) 12 | Linezolid | Vancomycin |
|---|---|---|
| Clinical success rate | 57.6% (95 patients of 165) |
46.6% (81 patients of 174) |
| Nephrotoxicity | 8.4% | 18.2% |
| Conclusion: Linezolid was superior to vancomycin for the treatment of MRSA nosocomial pneumonia. | ||
Skin and soft tissue infections
Linezolid is equivalent to vancomycin in treating complicated skin and soft tissue infections and superior to vancomycin in the treatment of infections due to Methicillin-resistant S. aureus (MRSA)4,7.
Recent research has found that patients who received linezolid for complicated skin and skin structure infection (abscesses, infected ulcers) were less likely to undergo additional surgical interventions during the treatment period of 4 to 14 days versus vancomycin-treated patients 13.
Better results with linezolid are related to the enhanced skin and tissue penetration of linezolid.
| Results of analysis of impact of linezolid versus vancomycin on surgical interventions for complicated skin and skin structure infections caused by MRSA 13 | Linezolid | Vancomycin |
|---|---|---|
| Clinical success rates at the end of treatment | 88% |
80% |
| Clinical success rates at the end of the study | 80% |
68% |
| Microbiologic success rates at the end of treatment | 83% |
68% |
| Microbiologic success rates at the end of the study | 71% |
60% |
| Patients who received linezolid had a lower probability of undergoing ≥2 surgical interventions during drug treatment. | ||
| Results of study evaluated linezolid and vancomycin for a lower-extremity complicated skin and skin structure infection caused by MRSA in patients with and without vascular disease.14 | Linezolid | Vancomycin |
|---|---|---|
| Clinical success rate among patients with vascular disease | 80.4% |
66.7% |
| Clinical success rate Among patients without vascular disease | 94.5% |
89.4% |
| Linezolid-treated patients had fewer IV catheter-site complications and less kidney impairment but more frequent thrombocytopenia than those who received vancomycin. | ||
Further reading
References
- 1. Takada H, Hifumi T, Nishimoto N, et al. Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis. Am J Emerg Med. 2016 Oct 29 PubMed
- 3. Abunasser J, Metersky ML. A comparison of linezolid with glycopeptides in severe MRSA pneumonia. Expert Rev Anti Infect Ther. 2009 Oct;7(8):951-5.
- 4. Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C; Linezolid CSSTI Study Group. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2005 Jun;49(6):2260-6.
- 7. Weigelt J, Kaafarani HM, Itani KM, Swanson RN. Linezolid eradicates MRSA better than vancomycin from surgical-site infections. Am J Surg. 2004 Dec;188(6):760-6.
- 10. Peyrani P, Wiemken TL, Kelley R, Zervos MJ, Kett DH, File TM Jr, Stein GE, Ford KD, Scerpella EG, Welch V, Ramirez JA. Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study. Crit Care. 2014 Jun 10;18(3):R118. PubMed
- 11. Fujii S, Takahashi S, Makino S, Kunimoto Y, Nakata H, Noda N, Sakurai K, Miyamoto A. Impact of vancomycin or linezolid therapy on development of renal dysfunction and thrombocytopenia in Japanese patients. Chemotherapy. 2013;59(5):319-24. PubMed
- 12. Chavanet P. The ZEPHyR study: a randomized comparison of linezolid and vancomycin for MRSA pneumonia. Med Mal Infect. 2013 Dec;43(11-12):451-5. PubMed
- 13. Duane TM, Capitano B, Puzniak LA, Biswas P, Joshi M. The impact of linezolid versus vancomycin on surgical interventions for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus. Surg Infect (Larchmt). 2013 Aug;14(4):401-7. PubMed
- 14. Duane TM, Weigelt JA, Puzniak LA, Huang DB. Linezolid and vancomycin in treatment of lower-extremity complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus in patients with and without vascular disease. Surg Infect (Larchmt). 2012 Jun;13(3):147-53. PubMed
Published: January 02, 2017
Last updated: January 02, 2017
