Linezolid – Considerations in the war on MRSA

A 45 year old man presents to your hospital with cellulitis of the leg with some small areas of ulceration. He’s had this before, and has always swabbed positive for MRSA (methacillin resistent Staphylococcus aureus). Sure enough his GP swabbed him 2 days ago and he is growing out MRSA again. His GP also started him on Doxycycline and Clindamycin, which had worked well for him before, but this time his swab results show resistance to all of the tested oral agents.

The patient looks clinically well, and is a good candidate for out patient IV therapy with vancomycin. But, just as you are considering placing an IV you remember an advertisement you saw in one of the throw away journals that grace doctor’s bathroom stalls everywhere. You remember a drug called linezolid (aka: Zyvox, Zyvoxid, Zyvoxam), is this another oral option?

Linezolid is currently the only antibiotic available in the class of drugs called oxazolidinones.

It inhibits bacterial protein synthesis through binding to the 50s ribosomal subunit. Linezolid is a bacteriostatic antibiotic.

  • Gram positive bacteria: Linezolid has broad clinical effect against most gram positive bacteria including Enterococcus (including VRE), Staphylococcus auerus (including MRSA), Streptococcus species, Nocardia, Listeria and Corynebacterium.
  • Gram negative bacteria: Linezolid is ineffective against most gram negative bacteria. It has no effect on Pseudomonas or Enterobacter sp. There may be some effect against Moraxella, Pasteurella, Fusobacterium, Legionella, Bordetella, Haemophilus influenza, and Capnocytophaga. It is not a primary drug for gram negative infections.
  • Mycobacterium: Linezolid is effective against mycobacteria and has been used as part of multi-drug treatment.

Linezolid resistance has been reported in a variety of gram positive bacteria, including linezolid resistant MRSA.

The most common side effects are GI upset, nausea and headache. Serious but rare side effects include thrombocytopenia, myelosupression, neuropathy, and GI bleeding.

Linezolid is also a weak monoamine oxidase inhibitor.

Linezolid is a monoamine oxidase inhibitor (MAOi). Contraindicated concurrent medications include tricyclic antidepressants, SSRI’s, SNRI’s, meperidine (Demerol), phenylephrine, and tyrosine rich foods.

Linezolid is not cheap! A 10 day course of 600mg BID (20 tablets) will run you about $2000.

Linezolid has a specific (and FDA approved) role in the treatment of VRE. Additionally it is active against most MRSA and may be useful for patients who cannot tolerate vancomycin or have contraindications to IV therapy. Linezolid is expensive, but may be cheaper than hospitalization or out patient IV antibiotic programs.

Oral medication therapies are certainly more convenient than intravenous medication. It is tempting to see linezolid as a convenience medication, but I personally think that this is a misguided approach. Linezolid resistance is possible, and indeed has been reported. In an era of limited new antibiotics and snowballing resistance patterns, linezolid should remain a protected antibiotic, used only when specifically clinically indicated.