The Post-Antibiotic Era

Since the first antibiotic (penicillin) was discovered by Alexander Fleming in 1928, which was then readily available to the public in 1943, we entered the antibiotic age wherein minor infections that could be fatal could be readily cured. However, at the same time, antibiotic resistance, and the speed of this, has meant that the production of new antibiotics has been a constant struggle to keep up.

The danger of antibiotic resistance has been a danger understood from the outset but generally ignored by the wider community. When penicillin was first released it could be bought over the counter and within 2 years resistance emerged. While antibiotics today are generally not so readily available, we still have the following problems leading to misuse and acceleration of resistance:

• Medical doctors incorrectly prescribing antibiotics to patients suffering from a virus (e.g. cold/flu), essentially acting as a placebo
• Medical doctors prescribing the incorrect antibiotic to a patient suffering a bacterial infection that they have not fully diagnosed
• Meat industries feeding livestock antibiotics, which are then released into water streams and consumed by humans through meat.

Unfortunately for us the bacteria can evolve resistance to new antibiotics much faster than we can research, test and produce new products. In addition to this, pharmaceutical companies are not actively persuing research into new antibiotics as companies lack economic incentive to do so. There are predictions that by 2050 as many as 10 million people a year will die from infections that have previously been treatable using antibiotics.

The danger of this situation has become more well-known (e.g. with public advertisements, main-stream news stories) however, is it a case of too little too late? Have you ever taken antibiotics prescribed by a doctor when you didn't need to? Do you think the developed world will take appropriate action to more strictly regulate the use of antibiotics before it is too late?

My doctor as a baby never prescribed antibiotics and my parents never gave me any because they new I would build up a resistance to them, which would hurt me in the future when I would need them more.

Antibiotics are more effective on me now (I think). Antibiotics ALMOST helped my bronchial spasms, but not really. my spasms got better and better, then they got really, really bad one day. So eh.

BadSheep said:

My doctor as a baby never prescribed antibiotics and my parents never gave me any because they new I would build up a resistance to them, which would hurt me in the future when I would need them more.

Antibiotics are more effective on me now (I think). Antibiotics ALMOST helped my bronchial spasms, but not really. my spasms got better and better, then they got really, really bad one day. So eh.

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While it appears your doctor and your parents ensured they didn't contribute to unnecessary antibiotic resistance, that's not how antibiotic resistance works. The bacteria evolves and then spreads, which means in the future you may become infected with an antibiotic resistant strain (the result of others using antibiotics) and suffer as anyone else would.

Bacteriophage said:

Bacteriophages could replace antibiotics. It's called phage therapy.

Quoting the Phage Therapy Center:

"Phage Therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. The bacterial host range of phage is generally narrower than that found in the antibiotics that have been selected for clinical applications."

Phages are modified to selectively eradicate unwanted bacteria. Bacteriophage therapy is routinely used in Eastern Europe, and more recently, Asia.

I suggest doing your own research. I still have a limited understanding of how they work.

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I hadn't heard of bacteriophages before, so did some reading (as you suggested) and it looks like the "post-antibiotic era" may simply be a transition into the "bacteriophage era".

Unfortunately, the baceriophages still have the same fundamental issue as antibiotics - the bacteria they are selected to kill can still evolve resistance. The resistance should at least take longer to occur than it has with antibiotics (due to the targetted nature of bacteriophages). Hopefully the use of bacteriophages in the future will use the history of antibiotic abuse to avoid the acceleration of resistance we have seen.

Lotus the Cat said:

Unfortunately, the baceriophages still have the same fundamental issue as antibiotics - the bacteria they are selected to kill can still evolve resistance. The resistance should at least take longer to occur than it has with antibiotics (due to the targetted nature of bacteriophages). Hopefully the use of bacteriophages in the future will use the history of antibiotic abuse to avoid the acceleration of resistance we have seen.

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Not exactly, but it's still sort of a problem. 'phages can evolve, just like any other virus, so they don't exactly have the antibiotic issue. Compared to the bacteria there are massive numbers of phages which undergo evolution much more rapidly. Essentially, they can only be resisted by a bacterial strain for so long. However, while this is fine for an individual who has a happily evolving phage killing their infection, for transmitted infections the specific phage administered therapeutically needs to be up-to-date, so to speak, with the strain's resistance. Because we won't know if what someone is infected with resists current phage therapies, this is a very difficult thing to keep on top of. Every time a bacterial strain becomes resistant to its therapeutic phage there'll be a lag phase while we find a new one that works and get it approved for administration (this can take years with an antibiotic). So while they're definitely much much better than antibiotics with regards to dealing with resistance and it's not exactly the same fundamental issue as phages have the inherent ability to evolve with their targets, the practicalities of using phages as the answer to resistance are still sort of awkward.

There are further issues, though. Imagine a doctor telling a patient, "I'm going to prescribe you a virus to help deal with your MRSA infection (for example)". People who know what a bacteriophage is and how it works might in theory be okay with this, but the general public? No way in hell - at least, not any time soon. We live in a time where anti-vaxxers still exist, so this would be a step way over the line and would end up with even greater distrust in medical care. It'd be difficult to introduce phage therapy in a way that doesn't cause at least a degree of backlash.

There's also the question of safety. A stable phage strain that works effectively against its target is pretty safe to use, but as I said earlier, these things evolve fast. Due to their typically very simple genomes and enormous replication rates, phages can undergo very rapid changes with little specificity or relevance to their role as an anti-bacterial agent. Could they suddenly start infecting eukaryotic (in this case, human) cells? Very unlikely, but not inconceivable, and very scary if it does happen. How about gut flora? Much more feasible. As much as we want these guys to be our friends, if they're administered routinely and in high quantities to an individual full of bacteria for them to replicate in, there's very likely to be some degree of mutation and somewhere along the line you're going to get a rogue phage or two that isn't working like the rest of them. If these phages become active against gut flora then that could have disastrous consequences for the host. While the sort of people who like to cause problems in medicine by sensationalist news stories and headlines and whatever absolutely love this argument, it's actually pretty valid and is a sort of spanner in the works for phage therapy.

I think phage therapy has a lot of potential and will eventually see use, but it has a lot of obstacles to overcome and the general public would need a lot of education on how these things work before they're actually viable for use.

Lotus the Cat said:

Do you think the developed world will take appropriate action to more strictly regulate the use of antibiotics before it is too late?

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It's less up to the developed world on the whole and more up to the medical community. For example, patients shouldn't be told not to take antibiotics for their colds or their flu because they shouldn't even have access to them for these things in the first place. Medical doctors regularly misdiagnose and and over-prescribe and they're the ones who need to get their act together. It is really not that difficult to tell when something is due to a bacterial infection or a viral infection, and simple tests can easily show what sort of resistances a patient's infection has. However, as patient throughput is key (due to strain in countries with free healthcare and financial gain in countries without (particularly in those where medication is expensive)), medical staff don't often the time to look at these things. As is often the case in the medical field, profit needs to take a back seat for a while in favour of what's actually good for the patients and, in this case, the general public.

All I know is that I am actually terrified of world where antibiotics are rendered moot.

It might be a little naive of me to say this, but with one's health "an ounce of prevention is worth a pound of cure."

Most of the people I know are the types who will still go to school or work if they don't feel well. (Unless they're really feeling unwell.) It's because they don't feel like they have much choice. Gotta work, gotta pay the bills, and there's not much you can do if, like one person I know, you've been told that you need to come into work unless you're vomiting. (And this is in a food service job!) So lots of people are out in public spreading whatever they have when they should be home and/or seeing a doctor.

shenanigans said:

Not exactly, but it's still sort of a problem. 'phages can evolve, just like any other virus, so they don't exactly have the antibiotic issue.

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Certainly the specific way in which a bateriophage and an antibiotic operate are different. However, I disagree with your comment that their fundamental issues are not the same. If bacteria could not evolve to develop resistance to a bacteriophage, then (as you point out later in your post) they would be much easier to implement as a replacement to antibiotics. However, they do. The fact that bacteriophages can also evolve to infect the bacteria again does not specifically solve this issue. Interestingly, you make the relevant argument yourself:

• A bacteriophage may evolve to attack good bacteria (e.g. gut flora), causing more harm than good.

In addition to this, there is no control over the evolution of the bacteriophage to your benefit. It may or may not happen, and the timescale is uncertain: it's not something you can rely upon. As a result, it is more likely going to be a case of catch-up in a similar manner to antibiotics, creating new bacteriophages to attack the evolved bacteria. This will still take time (although I expect much less time than an antibiotic).

There are further issues, though. Imagine a doctor telling a patient, "I'm going to prescribe you a virus to help deal with your MRSA infection (for example)". People who know what a bacteriophage is and how it works might in theory be okay with this, but the general public? No way in hell - at least, not any time soon. We live in a time where anti-vaxxers still exist, so this would be a step way over the line and would end up with even greater distrust in medical care. It'd be difficult to introduce phage therapy in a way that doesn't cause at least a degree of backlash.

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I only see this as being an issue early into the use of bacteriophages. When antibiotics are no longer an option and someone has a fatal infection, I doubt they will deny the use of a bacteriophage because they're afraid of a virus. After all, people undergo radiation therapy for cancer.

It's less up to the developed world on the whole and more up to the medical community. For example, patients shouldn't be told not to take antibiotics for their colds or their flu because they shouldn't even have access to them for these things in the first place. Medical doctors regularly misdiagnose and and over-prescribe and they're the ones who need to get their act together. It is really not that difficult to tell when something is due to a bacterial infection or a viral infection, and simple tests can easily show what sort of resistances a patient's infection has. However, as patient throughput is key (due to strain in countries with free healthcare and financial gain in countries without (particularly in those where medication is expensive)), medical staff don't often the time to look at these things. As is often the case in the medical field, profit needs to take a back seat for a while in favour of what's actually good for the patients and, in this case, the general public.

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I definitely agree with this, which is why two of my points in my original post touched on the issue of the medical community. Therefore, since they have failed to correctly administer antibiotics, knowing they are doing so, can they really be trusted to stop that behaviour on their own? I think greater regulation/accountability would still be required to ensure doctors don't simply continue to prescribe antibiotics as recklessly as they have in the past.