Analysis: The antibiotic course has had its day

[blutoski]

Article in BMJ, submitted for your information, no question from me is attached.

Title: Analysis: The antibiotic course has had its day

Summary:

With little evidence that failing to complete a prescribed antibiotic course contributes to antibiotic resistance, it’s time for policy makers, educators, and doctors to drop this message

URL: [The antibiotic course has had its day]

Blutoskitorial:
I'm going to level with you: I feel like it's opposite day.

 

[Lithrael]

I can’t access the paper. Does it explain how we all got the wrong end of the stick on that one?

 

[Trebuchet]

Article in BMJ, submitted for your information, no question from me is attached.

Title: Analysis: The antibiotic course has had its day

Summary:


URL: [The antibiotic course has had its day]

Blutoskitorial:
I'm going to level with you: I feel like it's opposite day.

The summary makes no sense to me.

 

[Trebuchet]

Ok, here's the publicly available text:

Antibiotics are vital to modern medicine and antibiotic resistance is a global, urgent threat to human health. The relation between antibiotic exposure and antibiotic resistance is unambiguous both at the population level1 and in individual patients.2 Reducing unnecessary antibiotic use is therefore essential to mitigate antibiotic resistance.

Avoiding overuse requires healthcare professionals and the public to be well informed about antibiotic treatment, as set out in the first objective of the World Health Organization Global Action Plan.3 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.”4 Similar advice appears in national campaigns in Australia,5 Canada,6 the United States,7and Europe.8 And in the United Kingdom it is included as fact in the curriculum for secondary school children.9

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. Without explicitly contradicting previous advice, current public information materials from the US Centers for Disease Control and Prevention (CDC) and Public Health England have replaced “complete the course” with messages advocating taking antibiotics “exactly as prescribed.”1011 We explore the evidence for antibiotic duration, clinical effectiveness, and resistance, and encourage policy makers, educators, and doctors to stop advocating “complete the course” when communicating with the …

Apparently the idea is that not completing the course allows the more resistant of the bacteria to survive, while completing it eventually kills them off. The authors say there's little evidence of that.

 

[Darat]

From the abstract it seems to indicate all they are objecting to is people being told not completing a course leads to resistance. Not that people shouldn't complete the course. It's a kin to our forum's "technically correct'.

 

[Loss Leader]

But there's evidence that not taking antibiotics for an infection is still dangerous to one's health, right?

 

[Darat]

But there's evidence that not taking antibiotics for an infection is still dangerous to one's health, right?

Yes.

 

[Elaedith]

I can’t access the paper. Does it explain how we all got the wrong end of the stick on that one?

It seems to be claiming that the bacteria causing the greatest threat today are opportunistic antibiotic-resistant species that replace antibiotic-sensitive species in the skin and gut during treatment. Hence the longer the treatment lasts, the more it favours selection for the resistant species.

Link to full article: https://www.bmj.com/content/bmj/358/bmj.j3418.full.pdf

 

[Lithrael]

Ah, so, the things that become superbugs are so ubiquitous in the human environment that antibiotics, no matter how well or poorly administered, are never going to ‘get them all’ then?

The point of the article is that antibiotic use’s role in creating these dangerous resistances is not avoided by taking antibiotics correctly?

 

[This is The End]

Article in BMJ, submitted for your information, no question from me is attached.

Title: Analysis: The antibiotic course has had its day

Summary:


URL: [The antibiotic course has had its day]

Blutoskitorial:
I'm going to level with you: I feel like it's opposite day.

Yeah, that's going to have to be peer reviewed to Tulsa and back for me to believe it. It runs contrary to everything we know about natural selection.

First of all, somewhat unrelated, the overuse of antibiotics 100% percent definitely causes antibiotic resistant bacteria to flourish. Full stop. If you dump tons of antibiotics into a river, the ratio of antibiotic resistant bacteria will rise. Both from the killing off of antibiotic susceptible bacteria and from the multiplication of antibiotic resistant because of the decrease in competition for resources because of that.

So don't let any of that intertwine with what they are claiming in the paper. They are not disputing any of that.

Now for what they are claiming.

Not all bacteria that are susceptible to antibiotics are so to the exact same extent. (Forget about mutations for a second.) If you take antibiotics it will kill some quickly, some not so quickly, and some not at all. That applies greatly to different species of bacteria. But it also applies to the same bacteria somewhat. And that is because some bacteria can be in a weaker state than others.

OK so you are targeting a specific bacteria in a human because of an infection. As you take the antibiotic, more and more of that specific bacteria will die off (and so will others, but lets forget about that for the moment). This takes time for most of them to die off. That is the "course" they are discussing. If you end the course early, less of them die off. They are not disputing that. Also if you end the course early, you will be somewhat better off no matter off because you killed off X number of bacteria. But the bacteria that are left will be ones that were either slightly more resistant than their sisters or were not in contact with the antibiotic as fast.

But here is the problem. If you end the course early AND one or some of the bacteria down the line (in other words, it was not killed off because you ended the course early) has an extremely problematic resistant mutation; that bacteria is going to then flourish. Hopefully they are not assuming that resistance is binary and not a range? Anyway, that might only happen in one in hundreds of thousands of people, so maybe they are just downplaying the odds?

So long story short. Antibiotic misuse in individual people might not be as dire as current science warns in relation to the manufacturing of antibiotic resistance. But don't for any reason confuse that with the importance of keeping antibiotics out of the environment.

 

[casebro]

Also, when you end the course early, what do you do with the left overs / You save the 1/3 of the course, and take it next time. Not enough to kill the germs off, only enough to give them something to evolve over.

 

[lomiller]

The exact origin of a anti-biotic strain of bacteria is a very rare event that in practice is difficult to trace to it’s exact origins. This makes that origin difficult to prove but our understanding of natural selection allows is to make some educated guesses wrt possibilities. IMO the relevant question here isn’t whether there is evidence that can prove the origin of an antibiotic resistance strain, but whether there is evidence we can EXCLUDE ending antibiotics early as a source.

The description of the paper seem to be saying that they can prove this in cases where treatment goes to long, but it looks like all they found was that bacteria that were already resistant become more prevalent not that this lead to a new strain of resistant bacteria.

A common error with hypothesis testing is that when there is insufficient evidence to disprove the null hypothesis people assume the null hypothesis is true, which is wrong. Science is usually more concerned with comparing competing theories to see which best fits the data and which is the most useful in terms of explaining and predicting outcomes. Even when we know there is something wrong with a theory we use and accept it if it fits most of the data and is useful in explaining g and predicting outcomes.

Science does have an element of what courts call “prima-fascia” evidence as well. If one side (the prosecution in a criminal case) presents positive evidence that seems likely “on the face of it” but may not constitute absolute proof, the burden of evidence shifts and it’s now up to the other side (the defence in a criminal case) to provide positive evidence of their own that the claim (charge) is false.

In this case what we know about natural selection tells us that “on the face of it” discontinuing antibiotic early seems to be one possible place where anti-biotic resistant strains arise. This means saying “there is not enough evidence to prove the original claim” is no longer enough, those that disagree now need to come up with positive evidence of their own to support their position and the two bodies of evidence are compared to see which is strongest.

 

[blutoski]

The exact origin of a anti-biotic strain of bacteria is a very rare event that in practice is difficult to trace to it’s exact origins. This makes that origin difficult to prove but our understanding of natural selection allows is to make some educated guesses wrt possibilities. IMO the relevant question here isn’t whether there is evidence that can prove the origin of an antibiotic resistance strain, but whether there is evidence we can EXCLUDE ending antibiotics early as a source.

The description of the paper seem to be saying that they can prove this in cases where treatment goes to long, but it looks like all they found was that bacteria that were already resistant become more prevalent not that this lead to a new strain of resistant bacteria.

A common error with hypothesis testing is that when there is insufficient evidence to disprove the null hypothesis people assume the null hypothesis is true, which is wrong. Science is usually more concerned with comparing competing theories to see which best fits the data and which is the most useful in terms of explaining and predicting outcomes. Even when we know there is something wrong with a theory we use and accept it if it fits most of the data and is useful in explaining g and predicting outcomes.

Science does have an element of what courts call “prima-fascia” evidence as well. If one side (the prosecution in a criminal case) presents positive evidence that seems likely “on the face of it” but may not constitute absolute proof, the burden of evidence shifts and it’s now up to the other side (the defence in a criminal case) to provide positive evidence of their own that the claim (charge) is false.

In this case what we know about natural selection tells us that “on the face of it” discontinuing antibiotic early seems to be one possible place where anti-biotic resistant strains arise. This means saying “there is not enough evidence to prove the original claim” is no longer enough, those that disagree now need to come up with positive evidence of their own to support their position and the two bodies of evidence are compared to see which is strongest.

This is where the authors are going with their analysis: the working assumption that prematurely discontinued antibiotic courses create or intensify resistant strains is undemonstrated; meanwhile, there's lots of evidence that the opposite is true (that high doses and long courses of antibiotics create or intensify resistant strains). It may be time to update prescription policy.

Just as an analogy, we've already updated chemotherapy guidelines in line with the 2nd model mentioned above. Lower doses, short courses have a better outcome for many cancer types/stages. Wired has a discussion about the chemotherapy application here: [A Clever New Strategy for Treating Cancer, Thanks to Darwin]. The insight appears to carry over to bacteria and viruses.

Here's the mechanism in question: the cells are not just trying to grow... they're competing with their peers as well. Superresistant strains are actually less competitive. So: one of the things that reduces proliferation of the superresistant strains is their non-resistant peers. Lower doses and shorter/cyclic courses keeps the total infection in check, while also allowing for the internal competition for resources to suppress/extinguish the superresistant cell line.

The historical approach to 'blast' the infection with enough antibiotic to wipe it out has that one loophole, which is that if at least one of the cells is already mutated to resistance, all this is doing is wiping out the competition and allowing the superristant line to thrive.



We need more clinical trials, but at the moment the literature may be at a tipping point, which is the authors' proposal in the opinion piece I linked to in the OP.

 

[lomiller]

This is where the authors are going with their analysis: the working assumption that prematurely discontinued antibiotic courses create or intensify resistant strains is undemonstrated; meanwhile, there's lots of evidence that the opposite is true (that high doses and long courses of antibiotics create or intensify resistant strains). It may be time to update prescription policy.

Just as an analogy, we've already updated chemotherapy guidelines in line with the 2nd model mentioned above. Lower doses, short courses have a better outcome for many cancer types/stages. Wired has a discussion about the chemotherapy application here: [A Clever New Strategy for Treating Cancer, Thanks to Darwin]. The insight appears to carry over to bacteria and viruses.

Here's the mechanism in question: the cells are not just trying to grow... they're competing with their peers as well. Superresistant strains are actually less competitive. So: one of the things that reduces proliferation of the superresistant strains is their non-resistant peers. Lower doses and shorter/cyclic courses keeps the total infection in check, while also allowing for the internal competition for resources to suppress/extinguish the superresistant cell line.

The historical approach to 'blast' the infection with enough antibiotic to wipe it out has that one loophole, which is that if at least one of the cells is already mutated to resistance, all this is doing is wiping out the competition and allowing the superristant line to thrive.



We need more clinical trials, but at the moment the literature may be at a tipping point, which is the authors' proposal in the opinion piece I linked to in the OP.

Thanks. That makes sense. Like I said I wasn’t able to read the full version just the synopsis. I still think the phenomenon I described happens a lot, but I rescind the suggestion that it may be happing here. The underlying argument as you describe it actually looks really interesting!