human biology - What does completing the course of antibiotics accomplish?

This article from the WHO states:

If you stop treatment early, there is a risk the antibiotics won’t have killed all the bacteria that made you sick and that it will mutate and become resistant. This will not happen to everyone – the problem is that we don’t know who can safely stop treatment early.

By taking the full course prescribed by your doctor, even if you start to feel better earlier, you increase the chances of killing all of the bacteria and reduce the risk of resistance.

1. A clarification: When the WHO says “[bacteria] will mutate and become resistant,” they are implying that using antibiotics will create a selective pressure for bacteria with antibiotic resistance, arising most likely through mutations, correct? Bacteria don’t mutate into antibiotic resistant strains in direct response to a drug; rather, antibiotic resistance is a phenomenon of natural selection. I’ve seen so many articles about antibiotic resistance worded this way and I feel it’s simply wrong.


2. Presuming I am correct about my first point, here’s my true question: Say you’re prescribed a course of antibiotics. It kills the bacteria that are not resistant to the drug and leaves those that have developed resistance behind. What does it matter if you finish the whole course? Taking more of the drug is not going to affect the resistant strain. The only rationale I can think of is that it would kill off any residual non-resistant bacteria and prevent them from gaining resistance (via conjugation) from the resistant kind. However, is this the only mechanism whereby completing the course prevents the rise of antibiotic resistance? How effective is this at all at preventing the rise of antibiotic resistance in the bacterial population in general (i.e. beyond the host)?

Answer

As anongoodnurse has mentioned in the comments, an incomplete course can allow weakly resistant stains to expand their population. As you mentioned, the antibiotic does not cause the bacteria to mutate but it kills all strains that do not carry the mutation that provides the resistance. This mutation arises randomly (in certain cases it can be acquired by other mechanisms such as lateral gene transfer).

Many antibiotics may not kill the resistant strains but may still impose some burden on their growth. Now, with a complete course you would have eradicated a lot of strains and only a few resistant strains would be left. The probability of extinction/eradication depends on how many individuals are present in a population. When you do a complete course, then the chances of extinction of the resistant strains due to random birth-death process (and attack by the immune system) would be high because of their low numbers. However, with an incomplete course these bacteria would quickly expand their population once the antibiotic is gone. Now, with the next round of antibiotic treatment you would have more number of resistant cells to kill. As again pointed out by anongoodnurse, this will lead to further selection of resistant strains.

There are additional factors:

• Microbial community (colony) is more than just a bunch of cells. They can protect each other.


• There are some cells called persisters which are not really genetically resistant strains but tolerate the drug because of adaptive phenotypes. Again, the microbial community plays some role here.