# Is there a realistic path from antibiotic resistance to pandemic?

By using antibiotics too frequently, some argue, we're setting the world up for a pandemic that we cannot treat.

Every time an antibiotic substance is used, the bacteria that survive reproduce.
Every time the new ones are introduced to stronger antibiotics, those that survive reproduce again.
Through this type of selection, as well as horizontal gene transfer, subsequent generations of bacteria grow stronger.
After years of this process - notably in densely-packed farms with little hygiene - we're left with bacterial infections we have no way to treat.

Hold on! We might not be able to treat these bacteria, but they've existed for quite some time; things seem (mostly) fine. None have, as of yet, become pandemics - prevalent over whole countries or the world. I want to know if claims that the world could face the consequences of resistant bacteria are credible - or if isolated incidents do not compensate for years of evolution in order to spread rapidly.

Is there a realistic path from drug resistance to pandemic? Is there any evolutionary reason why or why not this could occur?

• What definition of "pandemic" do you want to use? I mean, I think you could write an answer such that it's unlikely that we'll lose 3/4 of the human population to a drug resistant bacteria, but for many people in the civilized world, the possibility of a few million dying is enough to qualify as a panic inducing pandemic. – Cort Ammon Dec 7 '16 at 22:36
• @CortAmmon I defined it in the question - "prevalent over whole countries or the world" – Zxyrra Dec 8 '16 at 0:33
• Narrowing it down: would you consider flu to be prevalent? How about specifically H1N1? – Cort Ammon Dec 8 '16 at 1:23
• @CortAmmon Whatever you think is realsitic; as long as at least 50% of the country and / or world is affected. – Zxyrra Dec 8 '16 at 1:35

The concern is not that a single species of bacteria become pandemic, but the genes which provide resistance to antibiotics becomes pandemic.

It's not that E.Coli is going to take over the world, but that all those small outbreaks of disease we can easily contain to one patient, or at least one wing of a hospital, can no longer be contained, and we're back to the bad old days of ships being left at sea in quarantine, entire cities being wiped out by cholera, flocks of livestock dying of disease, etc.

Intensive farming itself seems to be the scariest worldbuilding scenario for this type of pandemic. Flocks or herds which may have numbered in the tens or low hundreds now number in the high hundreds or thousands. Destruction of a single farm used to mean that family was in trouble; now it means an entire city could be in food trouble.

So, while I don't see a plausible way for a single bacterial disease to become pandemic, I can imagine a situation where, over the course of a couple of decades, constant antibiotic use has caused the genes for antibacterial resistance to become pandemic, brought around the world by gut flora in humans and farm animals, incubated, tested, and proofed in the digestive systems of the entire planet.

Taking this as a worldbuilding question for storytelling and not a scientific question, because I am not a scientist: I would have a rolling snowball of minor outbreaks of antibiotic resistant bacteria start to pop up all over the world. Salmonilla grabs a resistance gene in France and starts causing problems. Cattle farms in Texas are suffering lost stock due to a disease the vets are struggling to contain, causing the price of beef to skyrocket. Pig stocks in China are being decimated by a disease and the state is putting price and travel controls in place to stop the spread.

The world in this story would start to crumble not from one massive infection, but by death by a thousand cuts, as our modern society of high-density farming and cities struggle to handle these vicious attacks which can no longer be contained easily.

• Since you emphasize that the danger of spreading resistance genes is not a single-species issue: Is gene transfer between different species of bacteria common? I am aware of bacterial conjugation but always thought that this occurred most often between bacteria of the same species. I am also aware that viruses may transfer genetic material and that certain bacteria can produce virus like agents that attack other cells. – 0range Dec 8 '16 at 18:43
• Conjugation is only one method of transfer; bacteriophages can transfer sections of DNA from one bacterial cell to another. Additionally, "competence" is the ability of a cell to take up extracellular DNA. Check out Griffith's experiment, where competence allows nonvirulent pneumonia to gain virulence factors from heat killed virulent pneumonia. According to Wikipedia (yeah, I know) Plasmids can be transmitted from one species to another. One plasmid, F-Pilus, even gives a bacteria a tool to spread it's plasmids more efficiently! – Zoey Boles Dec 8 '16 at 19:06

I am not that flavor of scientist, but from what I've read and discussed with those knowledgeable, there is at least one realistic mechanism, namely https://en.wikipedia.org/wiki/Bacterial_conjugation Some scientists are worried about widespread use of antibiotics in raising food animals (chicken, swine, cattle) puts us at risk; https://en.wikipedia.org/wiki/Donald_Kennedy is one who sounded the alarm in the US and tried to do something -- only to by stymied by agribusiness interests.

Where might this happen? IMHO, especially likely where chronically-antibiotic-treated animals were raised or slaughtered -- and specifically places where biocrud goes and isn't sterilized. A plague-infected rabbit gets washed into a manure lagoon (yes, those are a thing!)? Similar rats get into some spilled slaughterhouse waste, when a garbage truck overturns? It could be happening right now.

Tuberculosis is becoming increasingly antibiotic resistant. As is, tuberculosis isn't very transmissable. If that were to change for a viable sub population of one of the existing antibiotic-resistant strains of TB, we could be in for real trouble, especially in crowded cities.

OT: I think it's absurd that agribusinesses can buy these chemicals by the ton (making me less safe), but I can't buy even gram quantities (just in case), without finding a doc who will prescribe them to me.

No, it wont happen

When I pushed you for definitions of "prevalent," the answer you gave was "...at least 50% of the country and / or world is affected." Based on that definition, we wont even get close to that bar.

To look at how it could go, we can consider the flu. The flu is notoriously hard to vaccinate for, and gets transmitted every year. It can also kill, though typically only young and old and weak. However, the 1918 flu is seen as an exception:

The influenza or flu pandemic of 1918 to 1919, the deadliest in modern history, infected an estimated 500 million people worldwide–about one-third of the planet’s population at the time–and killed an estimated 20 million to 50 million victims. More than 25 percent of the U.S. population became sick, and some 675,000 Americans died during the pandemic. The 1918 flu was first observed in Europe, the U.S. and parts of Asia before swiftly spreading around the world. Surprisingly, many flu victims were young, otherwise healthy adults. At the time, there were no effective drugs or vaccines to treat this killer flu strain or prevent its spread. In the U.S., citizens were ordered to wear masks, and schools, theaters and other public places were shuttered. Researchers later discovered what made the 1918 pandemic so deadly: In many victims, the influenza virus had invaded their lungs and caused pneumonia.

50% is a really high bar for a disease that does serious harm to a species. In general, we're pretty good at defending against diseases that are deadly. As we see here, even the worst flu pandemic in history only got to about 1/3 of the population.

That being said, you can see why others put the bar far lower than that. A disease that killed 20-50 million people is frightening enough to cause changes in behavior. Those behavioral changes typically stymie the pandemic faster than any drug ever does.

• To clarify, 50% of the country and / or world includes country; it is clear that this is not a threat to the world, but what about a country? – Zxyrra Dec 8 '16 at 1:47
• Then, in that case, we can use the smaller number from the quote. The 1918 flu infected about 1/4 of the US. Influenza was even further from achieving the country threshold. – Cort Ammon Dec 8 '16 at 1:49
• I appreciate the quantitative data but I will be accepting a different answer because you focus on the influenza virus. The question specifically asks about gene transfer between bacteria, and other answers provide a plausible "yes" answer based on bacteria. – Zxyrra Dec 11 '16 at 5:24

# Not really

The risk isn't about pandemics, they're normally viral as bacterial infections are, on the whole, not as contagious.

The risk is about things that are currently minor no longer being treatable. Antibiotics are given as a matter of course to prevent post-operation infections for example.

The use of antibiotic prophylaxis (both intraoperatively and postoperatively) is accepted as the gold standard in orthopedic practice and is recommended by the most widely accepted consensus-based guidelines. -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596117/

It's this sort of use of antibiotics that's being threatened by resistance, increasing the risk of operations that are currently considered routine and setting back modern medicine by a couple of generations, not a pandemic of TB

TB is a bacterial infection. TB that affects the lungs (pulmonary TB) is the most contagious type, but it usually only spreads after prolonged exposure to someone with the illness.

With treatment, TB can almost always be cured. A course of antibiotics will usually need to be taken for six months. Several different antibiotics are used because some forms of TB are resistant to certain antibiotics. If you're infected with a drug-resistant form of TB, treatment with six or more different medications may be needed.

• Plague is an infectious disease that is caused by a bacterium, just saying. – r41n Dec 7 '16 at 14:20
• @r41n, as you say, however it's also as rare as hens teeth in places where there aren't a dozen other things that'll kill you first. TB is far more common which is why I used it as the example. – Separatrix Dec 7 '16 at 14:28

Yes, it seems to me the two things are obviously related.

Evolution adapts life to its environment, including any other lifeforms. Many of these lifeforms compete for resources (food, space, you name it). If life form A is unable to adapt or compete with life form B, it will disappear in one way or another.

Bacteria are everywhere, and some are a threat when our immune system is unable to cope with them, allowing them to reproduce unhindered inside of us. Science allows us to vastly enhance our survival rate when coming in contact with large numbers of those bacteria.

Since not only our immune system is attacking those bacteria, the evolutionary pressure on those bacteria is also increased. This essentially means that we are strengthening the bacteria that survive, much more as if our immune system alone would fight them. As long as we retain the upper hand, as long as science is able to come up with new ways to kill bacteria that get stronger every year, we are fine.

But...if this process will ever come to a relatively sudden stop, we're going to have a major pandemic on our hands. Our immune system is not used to such resilient bacteria, and will probably have zero chances against them. You can see this already happening all over the world.

480 000 people develop multi-drug resistant TB each year, and drug resistance is starting to complicate the fight against HIV and malaria, as well

Source

AFAIK, the big problem is that, as of now, mankind has no way to efficiently create new, stronger, antibiotics. One big leap in that direction would be nano-technology (still 50 or so years away), which would enable us to create antibiotics that are easily reprogrammed to adapt to new kinds of microbes.

The scary problem isn't necessarily the microorganism developing the drug resistance, but what ELSE it might pass that resistance to! Bacteria and viruses are notorious for crossbreeding with other related organisms. So if we make a staph bacteria resistance to every type of drug, can it pass that resistance on to something more contagious or lethal? This is of particular concern when animals are heavily dosed and are in tight confines with humans or other species, then you get cross species microorganism jumping. This is how the flu starts every year, jumping from the bird reservoirs into humans. H1N1 is another example, it contains parts of the flu that are normally found separately in birds, people, and pigs.

So a highly infectious, but not particularly lethal, bug might get increased lethality and drug resistance from other microorganisms, which would then turn it into a good candidate for a pandemic.

But the more likely outcome is that we just can't treat nosocomial (hospital acquired) infections folks pick up when they get a surgery or have to stay in the hospital. This would be bad for individual patients, but wouldn't create a pandemic as these drug resistant bugs don't normally get transmitted from person to person very easily. Multi-drug resistant TB would be a problem as that is contagious, but TB isn't very lethal, at least not in the short term, so quarantine could be a solution (basically we'd be back to dealing with TB like we did in the pre-antibiotic era with sanitariums).

Bacteria might exchange genetic code between DIFFERENT SPECIES OF BACTERIA. They share a plasmid, a small fragment of DNA code that might allow it to synthetize a certain protein or group of proteins responsible for resistence to a certain drug.

If some bacteria resists vancomicyn but does not resist tetracycline, while another one resists tetracycline but does not resist vancomicyn, they can BOTH share plasmids and give one another the resistence they lack. From now on, both lineages of different bacteria kinds can resist two of the most powerfull antibiotics in existence. Add a third bacteria and so on, and you get a super-powerfull bacteria.

Not only that, but they can share virulence genes. Virulence is describes how powerfull a certain microoganism is at infecting people. So, if a bacteria that is not a lot virulent, but resists a good ammount of antibiotic classes, meets a very virulent bacteria that has low resistence, theres a chance that they will share plamids and become both virulent and RESISTENT. Thats the recipe to a pandemic.