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.

4 thoughts on “Dead People Don\’t get Bronchitis | Thoughts on Zithromax”

  1. I’m not a doctor, especially not an EP. I am a patient with Congenital Long QT Syndrome. It amazes me that anyone would feel the need to even conduct a study such as this one, much less rig it to say what they want it to say. Zithromax has been on the Arizona CERT list since I was diagnosed 10 years ago as a drug to be avoided by people with LQTS. So have many of the non-drowsy antihistamines. Both of these are known to prolong the resting phase of the heart, pre-disposing the patient to a potentially fatal arrhythmia. If you prescribe them along with other drugs that the patient may be taking that also prolong the QT interval you compound the chances that a patients QT interval can reach a dangerous level and the patient is at risk of dying of Sudden Cardiac Arrest. People born with the congenital form of LQTS are especially at risk. However, given enough medications concurrently that prolong the QT interval can cause a person who does not have the congenital form of the arrhythmia to develop acquired LQTS.  Slightly more people die while taking a Z-pac than those who take Amoxicillin because Zithromax prolongs the QT interval and Amoxicillin does not. The same holds true with Levofloxacin because it prolongs the QT interval. It’s not rocket science and it’s not news. It has been understood that both Zithromas and Levofloxacin as well as four printed pages of other medications prolong the QT interval for years.
    On the other hand, I have fired a surgeon and a string of primary care doctors because they refused to acknowledge that I really can not take drugs that are known to prolong the QT interval. I have actually had a doctor tell me that he understood that I couldn’t take Zofran because it prolonged the QT interval so he was going to give me Ondansetron instead…Ondansetron in the generic name for Zofran. I called him on his crap and he agreed to give me Compazine , but then gave me Ondansetron instead. Doctors need to take it seriously. If you give a patient too many drugs that prolong the resting phase of the heart you risk your patient dying of Sudden Cardiac Arrest. If you give a patient with Congenital Long QT Syndrome drugs that prolong the resting phase of the heart, you risk causing  them to die of Sudden Cardiac Arrest.


  2. It is certainly appalling that docs would try to slip one by you.  Clearly you know your disease better than most doctors do (which is not a bad thing, I might add), so what is the harm to them if they listen?  I do agree that the deaths are overwhelmingly from prolongation of QT (I can’t think of any other mechanism the cardiac death rate would go up with Zithromax).  I hope you avoid bozos like the ones you described.
    Maybe we docs need to adopt a new litmus test for any antibiotic: Would I prescribe this if it could increase this person’s risk of death due to heart problems?  That might keep us from overuse. 

  3. JenniferDavisEwing

     I had an incident much like the one Lisa described.  She talked about how her doctor basically said “I understand you can’t take the brand-name drug, so I’ll just give you the generic form instead.”  My former neurologist (who “fired” me for “being a difficult patient”) wanted me to start using Trileptal.  The name sounded similar enough to Tegretol (carbamazepine), a drug I’d had significant difficulty with, that I asked him what the generic name for Trileptal was (oxcarbazepine).  I didn’t need a neuroscience degree to figure out that carbamazepine and oxcarbazepine must be closely related.  I told him “Oh, no…I was on Tegretol for six years and hated every minute of it.  I do *not* want to try Trileptal!”  He insisted, telling me it was a newer drug, and just because it was in the same family of drugs as Tegretol didn’t mean it would have similar side effects.  Grudgingly, I agreed to try it.  At my six month follow up, he smiled brightly and asked how I was doing–then had the nerve to look surprised when I told him I was having all the same problems I’d had with Tegretol.
    He “fired” me as a patient because as long as I nodded and smiled and agreed with everything he said, everythinng was wonderful.  The second I had a question or offered an opinion, suddenly I was a “difficult” patient.

  4. I had the same thoughts as Lisa. The problem is not a new one but may have been better served had it increased doctors awareness of drugs that increase the QT interval. I have one son whose long QT was dx accidentally and fortunately only has to avoid the drugs on the Arizona Cert list. Fortunately he had a ped that took this seriously and marked his records appropriately. I do worry about the transition to the adult doc and finding (and knowing how careful he will be) about prescribing meds for him. At school I simply said he was not to receive any drugs without running it by me.  

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