Quitting when you’re not really ahead

In my last post, I introduced the problem of antibiotic resistance. It’s important to note that resistance is something developed over time – some bacteria were never susceptible to certain antibiotics in the first place. For instance, if I’m one of the three little pigs, and I build my house out of bricks, all the huffing and puffing of one wolf isn’t really going to make much difference. Neither will fire. But if I’d built it out of logs, I might be safe from the wolf’s breath, but not from flames. Susceptibility is about what drugs can be effectively used against a pathogen, or cause of disease. Resistance is about the ability of a pathogen to lose susceptibility to a drug that was previously effective. If it never worked, the pathogen isn’t resistant.

That’s an important distinction because bacteria, when they share, can share resistance factors (plasmids) for antibiotics without any consideration for their own susceptibility. Jim, the reeking Escherichia, can pick up a plasmid for resistance to penicillin. It does Jim no good – Jim was never susceptible in the first place. The mechanisms that penicillin uses to attack bacteria, the specific protein structures that penicillin targets, aren’t present on Jim. Penicillin can’t target what isn’t present. But Jim can still take the plasmid, tuck it away, and share freely. Jim shares resistance that he doesn’t need – which, as I said before, is an enormous problem. I also said there was a bigger problem – you and I helping the bacteria.

Your doctor prescribes antibiotics. Now, there’s times when they’re needed and times when they aren’t (See “No the Z-Pack won’t treat the Flu”, and “SuperChickens?” for the latter), but we’re going to ignore those occasions. We’ll assume that your doctor is well educated on the dangers of antibiotic resistance and not only knows when to prescribe antibiotics and when not to, but even knows how to choose which antibiotic to prescribe. So the doctor sends you off to the pharmacy with your prescription and very clear instructions: “Take every pill, on time, as directed, even when you start to feel better, and finish this prescription!” You get to the pharmacy, where the pharmacist hands you your prescription and tells you, very sternly, “Take every single pill, on time, as directed, even when you start to feel better, and finish this prescription!” You shake your head and go on your way, doubtful that you’ll ever feel better.

What they don’t tell you, or maybe they do, but you don’t hear, because you’re all very busy people, is why you have to take every single pill on time and finish the prescription, as directed, even after you start to feel better. They don’t tell you about what the antibiotics do to the bacteria inside your body, or what the bacteria do in response. So you start taking them, because anything would be better than how you feel now. Every hour, though, you start to recover, and it doesn’t take more than a few days, maybe even just 2, before you’re having trouble remembering those pills. Especially if they’re big. Or you have to take them two or three times a day. Or both. Oh yeah, I know how it is. I’ve been there. And you forget. And you start feeling better. And you decide it won’t hurt to save them for the next time you get sick – save the copay, right?

Except, here’s what you might have learned if everyone hadn’t been too busy to tell you why you have to take the pills the way they tell you. Every day in your body, evolution is pushing bacteria forward to be better, stronger, more fit for survival. The ones that successfully reproduce, that divide to make another copy, to increase the population of bacteria, those are the fittest. They’re the best. You have bacteria that live inside of you, on you, around you, as a part of you. It’s your microbiome, and it’s shaped by everything you do, everything you eat, every move you make, and also by choices your parents made when you were tiny. In fact, there are more cells in and on you that are part of your microbiome than there are cells that are actually you. These cells are responsible for teaching your immune system how to respond to pathogens, they teach our bodies tolerance, they allow digestion of certain foods, and in some cases, the presence of one helps prevent the excess of another. Microbes are your friends.

But you’re sick, and you dislike microbes at the moment. There’s nothing wrong with that – you managed to get hold of a pathogenic microbe, a disease-causing bacteria that was stronger, more fit for survival, than the ones already present inside you. When your immune system met this bacteria, it started fighting. You’ve probably got fever, inflammation, and pain. Depending on where the infection is, you might have some sort of discharge – sinus infections produce nasty mucous, skin infections produce pus, etc. There might even be swelling. All of this is part of your immune system rushing to fight off the microbial invaders. If you weren’t miserable, you’d be dying. That would be worse.

So the doctor, who wisely knew which antibiotic to prescribe because tests determined which bacteria caused the infection, gave your immune system a boost. The antibiotic is chemical warfare. Or, if you dislike that imagery, antibiotics are assistants for immune cells. They come in and target bacteria specifically. In fact, most antibiotics work by targeting things in bacteria that the human (or animal) body lacks.

But we come back to the problem of susceptibility and evolution now. If the doctor writes a prescription for an antibiotic that targets Sal, but the bacteria making you sick is Jim, that antibiotic isn’t going to do much to make you better. If the doctor decides to write a prescription that will kill Sal, Jim, and Sue, then the antibiotic may well make you better, but it also risks making you sick when the balance in your body is thrown off (that’s why there’s a pro-biotics craze, and why, any time I take an antibiotic of any kind, I eat yogurt).

I said the doctor had prescribed the right antibiotic, so it was Sal making you sick, and the antibiotic is for Sal, not Jim. Let’s say you managed to get some bad chicken because a new guy at the local fast food place accidentally cooked the chicken in the fish vat, and it didn’t cook long enough or hot enough to kill the Salmonella inside the chicken, and you got sick (these things happen). Your immune system does what it can, but Sal just overwhelms you. The first antibiotic makes it in, and the sulfa drugs help wipe out everything in their path. But it only takes an hour or two for Sal and his family to reproduce (versus the 10 months that humans are pregnant, and the 11-15 years it takes to reach sexual maturity after birth). So if you ate one piece of chicken at 6 pm with just one bacteria, in 12 hours, there are 4096 bacteria in your system. That might be enough to make you sick. But 12 hours after that, when there are 16 million bacteria in your system, your immune system starts struggling to keep up, and you got sick. So the assistance of the medication is welcome, but it’s fighting millions of bacteria. If you waited 3 days to get to the doctor, Sal had the chance to make over 4 sextillion copies of himself before the antibiotics got on board (that’s a 4 with 21 zeros behind it, or 4,000,000,000,000,000,000,000). That’s starting with one bacteria, doubling every hour, for 72 hours.

OK, so let’s think about this for a minute. Four sextillion copies. The bacteria made a copy of itself every hour. Changes had to creep in. Not all at once, mind you, not big ones. But a copy of a copy of a copy starts to look pretty bad, and once you’ve copied a copy 72 times, even the best copier isn’t going to be perfect. So now there’s copies out there with little changes. Some of them will make absolutely no difference. In fact, odds are good that lots of them will make no difference. The whole process of DNA to RNA to protein is set up to allow for a certain amount of wiggle room, so that when little changes creep in, there’s room. But there’s only a little bit of wiggle room, and there’s been lots of wiggling. So there will have been changes that were bad for Sal’s offspring. Some of the four sextillion new Sals just aren’t as strong as Sal was. The immune system will get to them and take them out, if the immune system can just reach them (that’s a lot of cells. Good thing you have diarrhea. You’re getting rid of a lot of cells).

But in all of those wiggles, some of the wiggles will make some of Sal’s offspring more likely to survive. When the immune system comes looking, these new Sal Jrs have wiggled just enough to be able to hide better, or duck better, or fight better. They live where Sal died. And every hour, when the four sextillion cells divide, those changes get passed on. The weak ones die out, the Sals and Sal equivalents keep going, and the SuperSals keep getting stronger.

That’s when you take the first antibiotic. It takes 20 minutes to hit your system, and it wipes out the weaklings and a fair sized chunk of Sal and his buddies. It may even wipe out some of the SuperSals. Your immune system gets room to work, helps wipe out more weaklings, more Sals, and so on. But every hour, the survivors divide and make more. Your next dose of medicine comes after the Sals have had 8-12 generations to adapt to what you just threw at them. That’s not much, and the meds do a great job of killing off more, but every single time, guess who survives? That’s right – the strongest. The Super-Sals. The ones who know how to survive against the very medicine you’re taking.

Now, if you do what the doctor told you to do, and you take every pill on time, even when you feel better, and you finish your prescription as directed, then the antibiotics help your immune system do what it was struggling to do alone, and your body wipes out the infection, and eventually, may even get around to killing the super-sals. But what if you quit? What if, when you started feeling better, you stopped taking the pills? What happens then?

Oh, you feel better. You gave your immune system room to work, and it did a great job. But you didn’t finish the job. You quit before you were done, and you left the strongest to survive. The only bacteria left alive in your body now are resistant to the drugs you were taking. You quit, thinking you were ahead, but the truth is, you gave them exactly what they needed to take you out, because now, the doctor doesn’t have the tools needed to treat you when you get sick again. And you will – the new generation of SuperSals are going to keep growing and dividing. And every generation will have those wibbly wobbly errors. Yes, some will make them weaker, and even kill them, but most will not. Most will keep them SuperSals. And some will make them even stronger. Because you quit.

Which is why, my dearest friends and families, when you take antibiotics, I will hound you to take every single pill, on time, until the prescription is gone, as directed. Because otherwise, you’ve quit at the deadliest possible time. You’ve handed the bacteria everything they needed to become even more resistant to even more drugs – and to make you sicker still.

What if you do take your antibiotics like you should, but your doctor gives them for the flu? Watch for “No, the Z-Pack won’t treat the Flu”. And for more on antibiotic free meat, look for “SuperChickens?”