Longtime Docnotes readers know that I am a fanatic about antibiotic overuse. This relegion applies not only to WHETHER an antibiotic is prescribed, but which one.
I did a research project during my residency in which I demonstrated that physician prescribing practices are influenced by "detailing" as the pharmaceutical industry knows well. But I detailed generic medications. So over the course of a winter, I taught my colleagues about erythromycin, TMP/SMX (Bactrim) and amoxicillin. How to dose them, what they are effective for, etc etc. ... and through a grant from two local health plans, I purchased samples from the hospital pharmacy of these medications and placed them in the samples cabinet.
The results were that not only did the physicians give out more samples of the generic medications ... but that they wrote more prescriptions for them as well.
Like many of my little adventures (yes .. I'll finish cleaning the basement "real soon now") ... this one was never finished to the degreee that would make it a publication-quality paper ... but it was a fun and instructive project nonetheless. A core part of the eduction .. even back then (1996) was that the 1st line treatments for the most common conditions are NOT the higher priced "big guns." As the physicians built experience with seeing patients get better with inexpensive narrower spectrum agents ... a lifetime of better prescribing practice was (I hope) built.
Fast forward to 2004.
Well established protocols now exist for the treatment of community acquired pneumonia .. and most of them suggest that "a macrolide or doxycycline" be a component of the therapy. (or a newer quinolone .. but don't get me goin about them!)
There is rather little data to guide us in this choice, and despite ample marketing, and a significant difference in price, my choice predicably remains doxycycline. Azithromycin seems a popular choice for many other physicians .. and I think that the sense of security they get from the much broader spectrum helps physicians sleep better at night .. knowing that this medication "gets all those bugs."
But the "getting them all" mentality is not consistent with good, thoughtful practice. We need to treat with as NARROW a spectrum as possible .. and really think hard about what the likely organisms are ... not just shoot from the hip (with a shotgun) and hope that what's there is wiped out.
Challenged this morning by a thoughtful colleage to provide evidence for the long 1/2 - life of azithromycin correlating with clinically important increases in resistance (I often quote studies that demonstrate tissue levels of azithro persisting below MIC even 3 - 4 weeks after treatment is discontinued, which theoretically would account for significant resistance pressure) ... I've come up with a few papers that suggest that such a correlation does in fact exist:
Streptococcus pyogenes resistance to erythromycin in relation to macrolide consumption in Spain (1986–1997)
... From a pharmacodynamic point of view, other factors may have contributed to the selective process. It has been suggested that macrolide agents with low Cmax and long half-life (like bd or od macrolides) are likely to produce a longer selective window, which means longer bacterial exposure to resistance-selective concentrations.32 Long-acting agents optimize selective effects.33 In any case, either directly or indirectly, both bd and od macrolides appear to be the main reason for the increase in erythromycin resistance.
Read the whole paper .. as it's a great overview of an issue that is complex .. and quite scary. The authors are careful to avoid saying that there is clarity of causality (since correlation can never clearly determine causality) .. but this is certainly enough to support the hypothesis that there is a relationship.
There are other reports (here and here) that discuss the correlation between macrolide use and increaseing resistance .. and of course the well known study that demonstrated decreased resistance as macrolide use decreases.
The CDC's report on this highlights an alarming increase:
azithromycin and clarithromycin, +388%; quinolones, +78%; and amoxicillin/clavulanate, +69%. This increasing use of azithromycin, clarithromycin, and quinolones warrants concern as macrolide- and fluoroquinolone-resistant pneumococci are increasing.
... and this paper sums it up rather well: (my emphasis added)
... Antibiotic use in ambulatory patients is decreasing in the United States. However, physicians are increasingly turning to expensive, broad-spectrum agents, even when there is little clinical rationale for their use.
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