You often hear that an incomplete course of antibiotics can promote the emergence of drug-resistant bacteria.  Patients are told not to stop taking antibiotics just because you feel better but instead to always complete the full dosage.  This is obviously partly for the health of the patient.  But it is also said to guard against drug-resistance.

I have never been able to understand the logic.  So I sat down to try to figure it out.  I came up with one possible answer but it seems second-order to me so I am not sure if its the primary reason.

One thing that seems obvious is that every time you  ingest antibiotics you create natural selection pressure within your body that favors any drug-resistant mutants that are there.  This is why the headline cause of super-bugs is overuse of antibiotics.  For example antibiotics are often prescribed and taken for non-bacterial illnesses like the common cold.  Also, antibiotics are given to livestock that people eventually eat.

But this doesn’t get us to the recommendation to complete your course of antibiotics.  Since the problem is the antibiotics, it tells us to use them as little as possible.  How could it be that the first dose helps the super-bugs, but the last dose hurts them?  They are drug-resistant after all, right?

I used to think that it must be that the selection pressure increases the rate of mutation.  This may be true but I don’t think it’s enough to support the complete-course policy.  Suppose I am halfway done with the recommended dosage and I stop.  My usage so far has encouraged mutations and I may be infected now with a drug-resistant strain.  Now the mutation-inducing effect is irrelevant because the superbugs are already there.  Their natural growth rate is going to dwarf any additional growth due to mutations.

More generally, since every prescription of antibiotics is a public health cost, then every time I continue to take my doses I am creating the same externality.

I finally hit on one idea which has to do with competition within the body among bugs of differing levels of resistance.  Start with this observation.  If I have a super-bug in me and I continue to take anti-biotics, I kill off all the wimpy-bugs leaving the super-bugs to have free reign over my body.  Presumably they grow faster without the competition.  OK.  But that seems again to suggest that, at least from a public health perspective, I should stop taking the drug so that the wimpy-bugs can outcompete the super-bugs.

So we add one twist to the model.  Suppose that my body has a baseline system of defenses that can fight off any bad guy, super- or otherwise, as long as there are sufficiently few of them.  Then, if I stop taking the drug too early, my defenses may still overwhelmed by the sheer numbers.  All the bugs start growing again and if I started with just a few super-bugs in me, then when I start to show symptoms again I now have lots of them.  However, had I continued to completion, all of the wimpy-bugs would be gone and my body’s natural defenses could have mopped up the few super-bugs that were left hanging around.

It’s a coherent theory.  But I am not sure I believe that it is quantitatively important.  So I still find the advice a little mysterious.  Any of you know better?