A recent paper in the BMJ argues that there is little scientific evidence to suggest that completing a prescribed course of antibiotics has any impact on antibiotic resistance, and that health professionals should stop giving this message. Martin Llewelyn and colleagues state:
Public communication about antibiotics often emphasises that patients who fail to complete prescribed antibiotic courses put themselves and others at risk of antibiotic resistance. For example, in materials supporting Antibiotic Awareness Week 2016 WHO advised patients to “always complete the full prescription, even if you feel better, because stopping treatment early promotes the growth of drug-resistant bacteria.” Similar advice appears in national campaigns in Australia, Canada, the United States, and Europe. And in the United Kingdom it is included as fact in the curriculum for secondary school children. However, the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.
This is a narrative review and not a systematic review of the literature. It is intended to promote a particular perspective, and the authors make the following arguments:
- Concerns that too little antibiotics could lead to the survival or “selection” of resistant bacteria can be traced back to the discovery of antibiotics. However, there is a lack of evidence to show that failing to complete a course of antibiotics leads to resistance in that bacteria.
- Antibiotic resistance that develops spontaneously during treatment, and may be selected for is called “target selection”. It can occur with infections like malaria, HIV, tuberculosis and gonorrhoea. Appropriate dosing and often combinations of antibiotics are necessary when treating these infections to ensure resistance does not develop. However, most of the bacterial species that pose public health threats due to widespread resistance did not develop resistance this way.
- Taking antibiotics for any reason means that antibiotic-sensitive species and strains will be replaced by resistant species already present. The longer the treatment, they argue, the greater the antibiotic exposure, and the greater likelihood of the replacement of antibiotic-sensitive bacteria with residual, resistant bacteria.
- Antibiotics are typically prescribed for set durations (e.g., 7 days of amoxicillin). There is a lack of evidence to show that the currently accepted durations are the minimum required. Historically, courses of antibiotics were based on fears of undertreatment, and less about overuse.
- The idea that there should be standard course of antibiotics hasn’t been shown to be valid, owing to different patient and disease factors. Stopping antibiotics based on factors like fever resolution may be superior – and need to be tested.
- While there have been substantive efforts to reduce the initiation of antibiotics (e.g., Choosing Wisely), little has been done to reduce overuse once prescribed.
- The “complete your antibiotics” message has persisted and while it is simple, it is not supported by evidence.
- Research is needed to determine the most appropriate messages, such as “stop when you feel better”.
The media uptake to this opinion paper was quite remarkable – there were dozens of stories, suggesting, “Why you may not need all those days of antibiotics“, “Some Doctors Now Say to Stop Antibiotics When You Feel Better“, and “The Common Wisdom on Antibiotics Is Wrong“. But is it really wrong, and should prescribing and use change?
From one non-evidence-based recommendation, to another?
Let’s look at the areas of agreement, first. The standard advice to “complete your antibiotics to prevent resistance” is not based on scientific evidence. The idea that excessive antibiotics can be harmful is not a new idea. There is absolutely a downside to antibiotics – they can cause adverse effects, sometimes severe, and minimizing the duration of therapy can reduce the risk of harms. Where shorter courses of therapy have been shown to be effective, they can (and should) be recommended and used.
But should patients simply stop antibiotics when they “feel better”? While the authors of the paper noted that this approach also required research, it’s the main message that almost all of the media coverage focused on. And it’s a potentially dangerous message to amplify, as there is no convincing evidence that this approach is any better than the conventional one. For example, what does “feel better” mean? To one person, it might mean a fever breaking. To another, it might mean complete resolution of symptoms and a return to normal function. And in some cases, what might look like signs of infection can persist long after antibiotics can be appropriately discontinued. And this type of rule would be even more difficult to apply in young children, who may not be able to express their feelings of wellness. We need evidence for any stopping rule for each type of infection and antibiotic used. And until we have evidence to suggest that arbitrary and potentially subjective stopping rules are better for patients, we could be making matters worse.
Another consideration: What would become of unfinished prescriptions of antibiotics? While some people will return unused and expired prescriptions to pharmacies (most pharmacies will accept and dispose of them safely), others may keep the remainder of a prescription for future use, or, even worse, possible use by others. A “stop when you feel better” direction could lead to more inappropriate use, not less.
More evidence on duration of treatment is needed
Given the frequency with which we use antibiotics, and the justified concerns about growing rates of antibiotic resistance, we need more evidence to inform decision-making, and we need better adherence to the evidence that actually exists. If one in three antibiotic prescriptions are unnecessary, then let’s focus on stopping them before we start. Where there is evidence that shorter courses of antibiotics are as effective as longer ones, then we need to ensure that physicians are prescribing according to best practices. And where we don’t actually know the optimal duration of therapy, then we need research to answer those questions. Before we recommend a “stop when you feel better” approach to antibiotics, we need evidence that we’re not doing more harm than good.
Photos via flickr users Sheep Purple and Practical Cures used under a CC license.