This post is a part of our Bioethics in the News series
By Robyn Bluhm, PhD
It’s something we’ve all been told: be sure to finish taking your antibiotic prescription. Don’t just stop when you begin to feel better. Doing so, we’re warned, may mean that the bacteria causing the infection have not been completely eradicated. Once treatment stops, they will begin to multiply again, causing a relapse. Worse, it may result in the development of antibiotic-resistant bacteria, which is dangerous both to the individual taking the medication and to the public as a whole.
But a recent article in The BMJ argues against this common wisdom, saying that advice to “complete the course” is not evidence-based—and that doing so may actually have the opposite effect of increasing, rather than decreasing, the risk of antibiotic resistance.
I find this piece—and reactions to it in on the journal’s website—interesting for bioethics because it illuminates the complex relationship between evidence and patient care. The article recommends changing treatment practices because of evidence that they may do more harm than good, but doesn’t really have a plan for what to change them to. This conundrum leads the authors of the article to make some interesting, but incomplete, suggestions related to physician-patient communication and shared decision-making. The commentaries on the paper challenge both the authors’ claims about the available evidence and their suggestions about sharing doubts about current practice with patients.
Changing Clinical Practice?
The randomized controlled trial (RCT) is currently thought to be the “gold standard” of evidence in medicine. It is not uncommon for discussions of medical evidence to cite examples of treatments that were in common use before an RCT was conducted, that were then shown by the trial to be useless or even harmful. This time last year, I blogged about a report that suggested that there is no evidence that flossing your teeth has any benefits. In response to this report, a number of people suggested that we should just stop flossing. In the late 1980s, a large RCT showed that two drugs commonly used to treat arrhythmia actually increase the risk of cardiac death and the authors recommended that their use be discontinued.
The question addressed in the BMJ paper is more complex than either of these cases. The recommendation is not to stop using antibiotics altogether, but to change the way that they are used. And the recommendation is not based on RCTs, but on the lack of evidence for current practice; on the flawed reasoning that linked early discontinuation with antibiotic resistance; and on evidence that overuse of antibiotics is actually the most important causal factor in the development of resistance. The authors identify only seven conditions for which researchers have conducted RCTs that directly compared a shorter with a longer course of treatment. Moreover, even in cases where the shortest effective course of an antibiotic treatment for a health condition has been identified, it’s not possible to extrapolate from this situation to the use of other antibiotics, or the use of that antibiotic for other diseases.
The authors of the BMJ paper do emphasize that more evidence is needed. But until that research has been done (if it ever is done), it’s not clear how doctors should change their current prescribing habits. As the discussion in the article makes clear, the answer to this question will depend on a number of factors, including the kind of infection and the specific antibiotic being used. Moreover, it will depend on the individual patient, as “patients may respond differently to the same antibiotic, depending on diverse patient and disease factors” (p. 2).
Talking with Patients
Given the number of factors that might affect patient outcomes, it would not be surprising if the authors of the article were unwilling to make specific recommendations for clinical practice. In fact, they don’t make a recommendation in terms of what doctors should prescribe for their patients. Instead, they end their paper with a section titled “How should we advise patients?” While prescribing a medication regimen certainly counts as giving a patient advice (at least implicitly), they couch their discussion in terms of general communication strategies, rather than of specific practice guidelines. In this section of the paper, they suggest that part of the reason that the traditional advice to “complete the course” has been so resilient is that “it is simple and unambiguous, and the behavior it advocates is clearly defined and easy to carry out” (p. 3). In addition to recommending further research on the appropriate dose of antibiotic, the authors also recommend research to identify “the most appropriate simple alternative messages” (p. 3). One possibility is to tell patients to stop when they feel better–exactly the opposite of what we have generally been told. More immediately, however, they say that doctors should begin to educate patients about the problems with the traditional advice, telling them that antibiotic overuse is the real problem that leads to antibiotic resistance. They suggest that honesty about our current lack of knowledge is better than “simply substituting subtle alternatives” such as the instruction to “take exactly as prescribed” (p. 3).
Take as directed…
A number of the commentaries on the BMJ website express frustration with the article–and with the situation it describes. Some of the commentaries emphasize that the article title is misleading or that the article itself overstates the conclusion that can be drawn based on the available evidence. Others worry that patients will take this article (and the media coverage that suggests that they should stop taking their antibiotics when they feel better) as license to ignore their doctor’s recommendations. One commenter even suggests that patient-centered decision-making is dangerous, and an illusion, when there is still medical debate on a topic. Yet many also agree that there is a problem with current practice.
The problem is that, if Llewelyn et al. are even close to correct, there is no clear direction for physicians or for patients. Confusingly, this seems like a case in which the growing evidence leave us knowing less, rather than more.
Robyn Bluhm, PhD, is an Associate Professor in the Department of Philosophy and Lyman Briggs College at Michigan State University.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, September 7, 2017. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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References
- Bacon J. Feel better? Maybe you don’t need to finish those antibiotics after all. 27 July 2017. USA Today. http://www.usatoday.com/story/news/nation/2017/07/27/feel-better-maybe-you-dont-need-finish-those-antibiotics-after-all/515996001/.
- Bluhm R. To Floss or Not to Floss? That’s not the question. 25 August 2016. MSU Bioethics [blog]. https://msubioethics.com/2016/08/25/to-floss-or-not-to-floss/.
- Corley M, Guise T, Barlow G, Piddock L, Howard P, Brown N, Nathwani D. Re: The antibiotic course has had its day. 28 July 2017. http://www.bmj.com/content/358/bmj.j3418/rr-11. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- Daneman N. Re-Setting the Antibiotic Course – this time using a map and a compass. 01 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-29. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- Donn J. Medical benefits of dental floss unproven. 02 August 2016. AP News. apnews.com/f7e66079d9ba4b4985d7af350619a9e3.
- Ghafur A. Re: The antibiotic course has had its day. 02 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-32. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- Leber W. Re: The antibiotics course has had its day. 04 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-37. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- Llewelyn MJ, Fitzpatrick JM, Darwin E, Tonkin-Crine S, Gorton C, Paul J, Peto TEA, Yardley L, Hopkins S, Walker AN. The antibiotic course has had its day. 26 July 2017. BMJ 358:j3418 https://doi.org/10.1136/bmj.j3418.
- MacMillan A. 2017. Some Doctors Now Say to Stop Antibiotics When You Feel Better. 26 July 2017. Time. http://time.com/4875610/antibiotic-resistance-recommendations/.
- Parthasarathy KS. Sober statements in the article, but an attention grabbing, misleading headline. 15 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-40. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- Solari HG. Re: The antibiotic course has had its day. 03 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-35. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
- The Cardiac Arrhytmia Suppression Trial (CAST) Investigators. Preliminary report: Effect of Encainide and Flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. 10 August 1989. New England Journal of Medicine 321:406-412. http://nejm.org/doi/full/10.1056/NEJM198908103210629.
- Zwart S. Antibiotics: Doctor versus patient interaction. 08 August 2017. http://www.bmj.com/content/358/bmj.j3418/rr-39. Comment on: Llewelyn et al. BMJ 2017; 358:j3418.
MSU Bioethics 
I’m not sure I read this article as evidence that physicians know less than ever. The problem that has always confounded physicians regarding the “take the full prescription” is the knowledge that very few patients actually ever do take the full prescription. We then see them back in the office with a partially treated infection for which the original antibiotic doesn’t seem to work. While that evidence is surely anecdotal, it is evidence nevertheless, and forms the basis for physician recommendations when formal studies have not been conducted. Complicating this reality of practice is the problem of physicians over-prescribing in the first place. Many community acquired pneumonias are viral, as are most ear infections, sore throats and sinus infections, yet physicians blithely prescribe antibiotics for them all, despite clear evidence and guidelines that discourage this practice. Perhaps some of the patients who return with partially treated infections are people whose viruses have been inappropriately managed with antibiotics in the first place, and who now have secondary, resistant bacterial infections. Sorting out cause and effect would require patients in studies to be precisely diagnosed and closely monitored for compliance.
Conversations between physicians and patients about the limits of medical knowledge tend not to happen because doctors are too busy: not enough primary care physicians, too much employer emphasis on generating income. With more conversation, patients might be better prepared to wait out minor infections without antibiotics, with an agreed upon backup plan in case they don’t get better or in case a bacterial infection ensues. When a true bacterial infection is identified, a discussion about how long to take the medications makes sense, based on the patient’s particular circumstances and other health issues along with what other evidence might be available. As with most aspects of medical practice, the best treatment options for any one individual may not be applicable to everyone.
Harriet Squier
flowerdocs@yahoo.com
Yes, I think it’s probably more a case of realizing that we didn’t know what we thought we did than one of knowing less!
As for overprescribing antibiotics, a couple of the commentaries on the paper raised that point, as well, and at least one talked about the agricultural use of antibiotics – these are certainly bigger causes of the development of antibiotic resistance than “completing the course”.