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Antibiotics

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Dead People Don't get Bronchitis | Thoughts on Zithromax

It was during my residency that the first indication of heart toxicity of antibiotics affected me personally.  The threat was related to the use of the first of the non-drowsy antihistamines - Seldane - in combination with macrolide antibiotics, such as Erythromycin causing a potentially fatal heart arrhythmia.  I remember the expressions fear from other residents, as we had used this combination of medications often.  Were we killing people when we treated their bronchitis?  We had no idea, but we were consoled by the fact that the people who had gotten our arrhythmia-provoking combo were largely anonymous to us (ER patients).

Fast forward to 2012 and the study (published in the holy writings of the New England Journal of Medicine) that Zithromax is associated with more dead people than no Zithromax.  Here's the headline-provoking conclusion:

During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002).  Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. (Emphasis Mine).

It turns out that they also indicted Levofloxacin, another commonly-used antibiotic as being roughly as risky as Zithromax.

While this is good fodder for the headlines, it hits me right where I live.  I constantly have patients coming into the office with symptoms that make them feel they need an antibiotic, many of whom have gotten Zithromax.  I wrote an early post on the subject of the temptation to give a Z-Pak in the gift basket we give our patients for walking into our office:

Which brings me back to the Z-Pak.  Zithromax (Azithromycin) is truly a great drug, and the friend of many doctors.  It treats strep throat, skin infections, sexually transmitted disease, whooping cough, and certain kinds of, yes, bronchitis.  It is very easy to take, requiring a total of 5 doses over 5 days, and it comes in a handy-dandy pack with a catchy name.  When a patient tells their friends and family, “I got a Z-Pak,” they are much more impressed than if they say, “I got an antibiotic.”

I ended with a warning:

So, when you have a cough and go to the doctor, get the diagnosis of bronchitis, and get a Z-Pak think of me.  You may want to ask if you really need the antibiotic, or if you can wait to see if it will go away without it.  In many, if not most cases, you might just as well meditate with the word “Zithromax” as your mantra, or burn the pills in a sacrifice to the Greek god Z-pacchus.

God bless America, land of the Z.

I even wrote a poem for it:

Six little pills at the patients’ insistence Six little pills should we now keep our distance? Six little pills we’ll rue your existence If Six little pills are paths to resistance.

Oh Zithromax, Zithromax! You make us desirous Against our best judgment to cover a virus Oh Zithromax, Zithromax! Your pills in a pack So oft make the best doctor act like a quack.

Yet there are good reasons to use antibiotics like Zithromax, so I am left with the dilemma of how to interpret the results.  Is this a real problem, or is it simply a retrospective study by a bunch of scientists wanting to make a splash?  I have to answer this question because I have to decide whether or not I am going to write a prescription for this medication, risking a "is my doctor trying to kill me?" look from my patients.  I have to prescribe antibiotics, but in doing so do I feed the fortunes of personal injury attorneys who realize the two following things:

  1. Doctors prescribe Zithromax by the bucket
  2. Every one of the patients who get a Zithromax prescription will die.

I give it 2 weeks before we see a commercial soliciting business for people who have loved ones who took Zithromax and then had heart attacks.

To figure out how to deal with this dilemma, I went to some of the experts among the med blogger community.  Marya Zilberberg is an epidemiologist at the University of Massachusetts and author of the blog, Healthcare, etc.  She even wrote a book about how to properly read medical literature (a book that I need to read, actually).  In short, she's brainy.  She wrote a post entitled, Why I have the propensity to believe the azythromycin data (I told you she was brainy), in which she states the following:

But there is a second, possibly more important reason that I am inclined to believe the data. The reason is called succinctly "propensity scoring." This is the technique that the investigators used to adjust away as much as feasible the possibility that factors other than the exposure to the drug caused the observed effect.

She then quotes a part of her book (which I definitely need to read) about propensity scoring.  Tying this to the Zithromax study:

And if you are able to access Table 1 of the paper, you will see that their propensity matching was spectacularly successful. So, although it does not eliminate the possibility that something unobserved or unmeasured is causing this increase in deaths, the meticulous methods used lower the probability of this.

So by this I am led to believe the data have some beef behind them.  I am also much more likely to use the word "propensity," as it may make me sound as brainy as Marya.

On the counterpoint is Dr. Wes, one of the old guard bloggers (who I've drunk beer with), who has been blogging since the internet was run by carrier pigeon.  Dr. Wes is a cardiologist who specializes in heart rhythm problems, the kind of problems that presumably killed the people in the NEJM study.  He wrote an article, How Bad is Azithromycin's Cardiovascular Risk?  in which he admits the potential risk of this kind of antibiotics, but questions the data methods of the study:

What was far scarier to me, though, was how the authors of this week's paper reached their estimates of the magnitude of azithromycin's cardiovascular risk.

Welcome to the underworld of Big Data Medicine.

He minces no words as he continues:

To think that despite all of the confounding factors that the authors had the balls to state that "as compared with amoxacillin that there were 47 additional deaths per 1 million courses of azithromycin therapy; for patients with the highest decile of baseline risk of cardiovascular disease, there were 245 additional cardiovascular deaths per 1 million courses" is ridiculous.  Seriously, after all the manipulation of data, they are capable of defining a magnitude to three significant digits out of a million of anything?

His conclusion is that this study is basically a bunch of sensationalized data meant to get headlines (which it did).  I think he needs a beer.  Call me, Wes.

So I am left to sift through these two opinions of two people I respect, and do so in the backdrop of patients wanting antibiotics and lawyers dreaming of big yachts.  What do I think?  I think we can't tell what the truth really is.  Yes, the folks who wrote the study are probably gunning for headlines (as is the NEJM), but it is also a fact that antibiotics can be dangerous, and all drugs come with some sort of a price.

I come back to advice I gave in an earlier post: When all else fails, do nothing.  Don't give an antibiotic unless it's needed, and don't ask for one if you don't need it.

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Catching Some Z's

“I’ve got bronchitis and my doctor gave me a Z-Pak.”

I hear this from friends, from family members, and from my patient who went to the urgent care over the weekend.  I smile and don’t say what I am really thinking:

Bronchitis:  noun  -  inflammation of the mucous membrane in the bronchial tubes. It typically causes bronchospasm and coughing Translation: a loose cough.

This is one of the most common tricks we use as doctors: stating the obvious using a Latin or Greek word to describe the symptoms and call it the diagnosis.  The suffix -itis refers to inflammation. Dermatitis is one I frequently use: someone comes with a rash (skin inflammation) and I tell them it’s dermatitis, which simply means...drum roll please... it’s a rash.  If you have sore throat, we call it pharyngitis, which means inflammation of the back of the throat. The suffix -algia, which which means “painful” is also quite useful.  Headaches can be called cephalgia, joint pain, arthralgia, and proctalgia is a pain...where the sun don’t shine.

In all of these circumstances, of course, the person is quite aware of their cough, rash, sore throat, headache, joint pains, and pain in the butt.  Why call it by it’s fancy name?  Two reasons: 1.  it sounds better when we tell the patient, and 2. we can bill for it.  It does not, however, say anything about prognosis, treatment, or expected course; it simply states what is obvious.

Which brings me back to the Z-Pak.  Zithromax (Azithromycin) is truly a great drug, and the friend of many doctors.  It treats strep throat, skin infections, sexually transmitted disease, whooping cough, and certain kinds of, yes, bronchitis.  It is very easy to take, requiring a total of 5 doses over 5 days, and it comes in a handy-dandy pack with a catchy name.  When a patient tells their friends and family, "I got a Z-Pak," they are much more impressed than if they say, "I got an antibiotic."

The problem with Zithromax, however, is that it spends very little time in the blood stream, going directly inside the cells of the body and spending a very long time there, often away from the infection itself.  This is OK for certain types of infections, but not so good for ones that involve infected extra-cellular fluid, such as infected mucous (AKA sputum, green snappers, loogies, whatever you want to call them).  This means that it’s a fairly weak drug for middle-ear infections or sinusitis, and only marginally good against many forms of bacterial bronchitis.  These, of course, are the main things for which the drug is prescribed.

Why?  Why do people get a medication for conditions that are not well-treated by that medication?  For most of these conditions, bronchitis included, the real cure for them is simple: breathing.  You just have to keep breathing long enough while your body fights off the infection like it was designed to do and the infection will go away.  Skeptics out there who want to try not breathing will soon find out that this approach is not successful.  Trust me.

So what difference does it make to take a Z-Pak while you breathe?  In many, if not most cases, it has no benefit.  It does, however, makes the patient feel like the doctor is doing something for the patient, who paid the co-pay and waited 2 hours in the office.  There are still a good number of people who are dissatisfied when they spend their tie and money only to be told to breathe. Plus, modern medicine has indoctrinated doctors and patients with the belief that doing something is always better than just breathing for a little longer.  This untrue, but highly profitable belief is hard to dispel.  The patient got a Z-Pak and they got better!  Both doctor and patient make this causal connection, and both are happier for it, but breathing gets the shaft because the Z-Pak gets all the credit for what it did.

I once cynically said that Zithromax is the antibiotic you prescribe when you don’t think the person needs an antibiotic.  While that’s not completely true (I think it’s a good choice for strep, and for a chronic cough), I do think it’s the reality seen in primary care offices, urgent cares, and emergency rooms across this great land.  In fact, my PA told me on the week leading up to Christmas that she had joked with a colleague that they call this week “Zithromax Week,” as many prescriptions are written “just in case,” or “to make sure they are healthy for the holiday.”  I’m sometimes guilty for that one.  I do run a business, you know.

Of course, there is definite risk in taking an antibiotic when it’s not needed.  I’ve read (but am to lazy to find the citation) that overuse of macrolide antibiotics (of which Zithromax is the dominant drug) is one of the main sources of antibiotic resistance.  People can have side effects from the medication as well.  But as is the case with donuts, not exercising, spending time reading blogs when you should be otherwise productive, or watching reality TV, the inertia of the bad choice in the moment totally overwhelms any desire to do the right thing.  "Come on," the doctor says to himself, "The world won't fall apart if I give a Z-Pak to this one patient!"  Krispy Kreme donuts is depending on you to make a similar argument.

So, when you have a cough and go to the doctor, get the diagnosis of bronchitis, and get a Z-Pak think of me.  You may want to ask if you really need the antibiotic, or if you can wait to see if it will go away without it.  In many, if not most cases, you might just as well meditate with the word “Zithromax” as your mantra, or burn the pills in a sacrifice to the Greek god Z-pacchus.

God bless America, land of the Z.

*Obligatory disclaimer: This is not meant to convince people to not take prescribed medications.  I don’t know about your own personal medical conditions.  It is just meant to make you appropriately skeptical, and perhaps ask your doctor, “can I wait to take this?” or “do I really need this?”  If they say “yes, you do need it,” take the dang Z-Pak!

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