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.

Otitis Media: How to treat your patients right and do the right thing

In a busy emergency department nothing is as wonderful as a simple and straight forward case. Otitis media used to be that case; a child is crying, the ear is sore and red, hand over a prescription for penicillin and the job was done. Happy parents, happy doctor, happy child….oh wait, the child was still unhappy but 2 out of 3 isn’t bad.

Mounting evidence and experience in European countries has shown us that immediate treatment of otitis media with antibiotics is probably not warranted. In a modern immunized society the majority of cases of OM are essentially benign self limited illnesses that don’t require treatment. In many North American emergency departments physicians have slowly been backing off of antibiotic treatment for OM. This past January 2 separate studies were published in the NEJM that have again shifted us back towards antibiotic prescribing for OM. Separate studies by Tahtinen and Hobermen both seemed to show a benefit in treating children less than 2 with a 10 day course of amoxicillin-clavulanate. There was much analysis of these studies, perhaps the best is by Dr. David Newman, and in the end it seems that perhaps there is a small reduction in symptoms when children are treated with antibiotics at a cost of significant antibiotic associated side effects, most commonly diarrhea.

Physicians are confused, we don’t know what to do, we try to read the parent and sense what they want and do what we think will make them happy. Parents are confused, sometimes doctors tell them their kids need antibiotics, sometimes they withhold antibiotics, it doesn’t make sense to them. What was once a lovely and brief encounter is turned into an emotionally turbulent episode of hand wringing, half explanations and crying children; a doctor who is unsure what to do, and a parent who is aggravated by the seeming randomness of the situation and a conflict around antibiotics.

The problem with ear infections is that they hurt, they hurt in the same way it hurts when a sadistic dentist blows compressed air onto a freshly drilled tooth (why do they do that!?). Adults with an ear infection want a shot of morphine, kids get a pat on the head and an ‘it’ll be okay buddy’. The only reason that anyone takes a marginal reduction of symptoms in an OM study seriously is because the symptoms are terrible and because we don’t treat the symptoms. It seems ridiculous that we are willing to accept a 15% risk of diarrhea with amoxicillin-clavulanate for 12 hours less of symptoms, particularly when the symptoms can be treated (if only we decide to treat them).

Here’s what I’ve found helpful in turning otitis media back into a great emergency department encounter:

  1. When I walk in the room and see a crying child with a bright red and bulging TM I say Wow! That looks really sore, we need to do something to get you feeling better right away!
  2. I always carry a couple of sterile ampules of 2% lidocaine in my breast pocket, and as long as there is no allergy I put 2-3 drops in the ear (there are commercial products designed for this, but they are expensive and single use lido works just fine). Then I tell the parents, just to keep him still for a minute while I go get a sticker to distract the child.
  3. When I get back into the room no one wants to talk about antibiotics because the child is now happy and smiling. What they want to talk about is the magic pocket drops and where they can get some of their own.
  4. I then give the child 15mg/kg of po acetaminophen.
  5. Then I say to the parents; Now that he’s feeling better we can talk about what to do. These days in children who are immunized ear infections are not dangerous and get better with time, people sometimes worry that they might turn into meningitis but I can reassure you that that is not going to happen. The biggest problem is that ear infections are painful so the first thing we need to talk about is how to control the pain…I give them a talk on using proper weight based doses of acetaminophen or ibuprofen and a topical agent like the lidocaine drops or a commercial alternative and that typically symptoms last 5 to 7 days…When it comes to antibiotics the studies that are out there don’t show a lot of benefit and they do show a lot of children getting side effects like diarrhea, so I like to start with getting the child feeling better with pain control. I’m not dogmatic about antibiotics though, if you are worried he is not getting better we are always happy to see him again and reassess the situation or if you would like I will even write you a prescription for antibiotics you can fill in a couple of days if things are not getting better.
Almost no one takes the delayed antibiotics script, and often when they bring in another child for an ear infection the parents decline antibiotics and ask for pain control options instead. The whole encounter takes about 5 minutes. It is much faster and easier to control the pain and explain the options than to have a tense antibiotic associated stand-off to the tune of a screaming child.
And ahhhhhhhhh, that’s the sound I remember from the old otitis media visits, happy parents, happy doctor and happy child, oh wait this time we are 3 out of 3….

Factoid: Kanavel’s Signs

  1. Intense pain with extension of the digit
  2. The digit is held in passive flexion
  3. Fusiform (uniform) swelling of the digit
  4. Percussion tenderness along the course of the tendon sheath