No new antibiotics since the 1970's?

[Dr. Trintignant]

A co-worker claimed the other day, as part of an argument that pharmaceutical companies want to keep people sick, that no new antibiotics have been developed since the 1970's. This set off my skeptical alarm bells, but the information I'm getting via Google is pretty slim. I have a few questions:

- Any idea where the claim comes from? It sounds like something out of Michael Moore's movie Sicko, which my co-worker has seen but I haven't. But then, the co-worker is filled with any number of "weird views on healthcare", so it could have come from a number of sources.

- Is there any truth to it? One site I saw mentioned that no new class of antibiotics has been developed since then, but that sounds like a very different claim (plus that site looked a bit fishy itself). But then, I don't know precisely what a "class" of antibiotics means.

- Even if there is a grain of truth to it, what explanations are there other than the (fairly stupid, IMHO) one that drug companies don't want to cure their patients. Has basic research been underfunded over the past few decades? Are we running out of differentiating factors between prokaryotic and eukaryotic cells? Is there no money in antibiotics, due to expensive testing or weirdnesses in patent law? Etc.?

Thanks for any answers.

- Dr. Trintignant

PS: If the claim is simply outright false, and there are counterexamples, can you cite some?

[casebro]

Anything for which there are no generics is probably new for this game. How about Ciprofloxin, Penicilin VK, Mipro-sumthin for staph....

[joobz]

Anything for which there are no generics is probably new for this game. How about Ciprofloxin, Penicilin VK, Mipro-sumthin for staph....
Add to that list
Cefaclor (approved 1979)
Telavancin (Approved Just this month 09/2009)
TIGECYCLINE (approved 2005)
CEFIXIME (approved 1989)


Hell, that's just a brief list
go here, and check out the antibiotics that are (or have been) in use.
http://en.wikipedia.org/wiki/List_of_antibiotics

Antibiotics make money. Why wouldn't companies develop new ones?

[Dr. Trintignant]

Playing devil's advocate here (my co-worker is quite rational and intelligent overall, just prone to believing in mild conspiracies): it looks like most of the antibiotics mentioned are variants of existing ones. For instance, according to Wikipedia, telavancin is a synthetic derivative of vancomycin, which was approved in 1958.

But maybe I shouldn't assume that being non-derivative is a prerequisite for being novel--if the major classes of antibiotics are mostly fleshed out at this point, then perhaps all we should expect are derivatives.

- Dr. Trintignant

[joobz]

Playing devil's advocate here (my co-worker is quite rational and intelligent overall, just prone to believing in mild conspiracies): it looks like most of the antibiotics mentioned are variants of existing ones. For instance, according to Wikipedia, telavancin is a synthetic derivative of vancomycin, which was approved in 1958.

But maybe I shouldn't assume that being non-derivative is a prerequisite for being novel--if the major classes of antibiotics are mostly fleshed out at this point, then perhaps all we should expect are derivatives.

- Dr. Trintignant
Don't confuse categories of drugs with "no new drugs". Derivitives can have highly varying properties.
They can be designed to have enhanced function and/or less prone to resistence emergence. Bone cement and soft contact lenses are both made from the same class of polymer (acrylates-methacrylates), but thier properties are completely opposite.

Now, certainly "new classes" of drugs are also being studied, but those typically take more time to see clinical use. (quatrinary amine systems, peptide antibiotics are a couple of examples).

[Criticalist]

While its true that there have been relatively few new classes of antibiotics discovered since the 1970's, there have been many new types. When we talk about class, we are referring to the mechanism by which the the antibiotic kills the bacteria; for example penicillins act by binding to proteins in the bacterial cell wall. There can be many different types of antibiotic in one class, which may have very different effects. So, benzylpenicillin is effective against only a few strains of bacteria, while ticarcillin, also a penicillin, is effective against a much wider range.

So, just because a new drug is part of an existing class doesn't mean it doesn't have an important therapeutic role,as it may be effective against bacteria that others of its class are not. Its also true that new and effective antibiotics will make money, so there is no real justification for a conspiracy theory.

On the other side of the coin though, it is true that we do want to see new classes of drug available, as bugs which develop resistance to one drug in a class may go on to become resistant to the class as a whole. There are some new classes on the horizon, but relatively few. This may be due to the costs and time involved; it has been estimated it takes 12 years and 250 million dollars to bring a drug to market, and only a third of those will show a profit. Thus drug companies may be more likely to want to stick to variants of known drugs rather than looking for brand new types.

[Dr. Trintignant]

Derivitives can have highly varying properties.
They can be designed to have enhanced function and/or less prone to resistence emergence.

Is reduced resistance emergence a common target for derivative drug research? Obviously, antibiotic resistance is a major problem so I could see how drugs that are less prone to this would be a well-studied area. And derivative drugs might have the advantage that their other properties are well known.

Now, certainly "new classes" of drugs are also being studied, but those typically take more time to see clinical use. (quatrinary amine systems, peptide antibiotics are a couple of examples).

Thanks; I'll look into those examples.

- Dr. Trintignant

[joobz]

Is reduced resistance emergence a common target for derivative drug research?
Depends on the group. On the whole, strategies to reduce resistance emergence is a big area of work right now. For instance, one way microbes can become resistant is through enhanced eflux pumps. These work to decrease the cytosolic concentration of antibiotic and thereby become more resistant.

Antibiotics (or coadministered drugs) which can function at these pumps to reduce thier efflux potential is an active area of research.

Similarly, some drug resistance works by changing the binding pocket that the antibiotic works on. If that pocket is changed, theoretically, there should be a new type of drug that could sit in the new domain and ellict similar types of antibiotic resistance.

Finally, I've seen some groups look at using Siderophors (iron binding chemicals) that bacteria use to intake iron. They are attempting to create adducts that use the same structure (so the bacteria will take it in) and deliver antibiotic capacity. In this way, the bacteria will have a hard time adapting to the drug, since the siderophor binding/intake system is needed for the bacteria lifecycle. Any mutation that reduces this intake will also likely reduce it's ability to grow and function. (as it won't have the needed iron).

[theprestige]

Why should there be lots of new antibiotics?

I mean, it's not like we're adding a lot of new elements to the periodic table. Why should there be an unlimited number of biochemical reactions that have useful medical effects against that class of biochemical systems known as "biotics"?

There's only a limited number of ways you can burn things. There's only a limited number of ways to make an acid. There's only so many variatons on the chemical compound known as "milk". Why do we have to accept, a priori, the assumption that scientists should continue to discover or invent antibiotics at a constant rate?

Why haven't we invented any new wheels lately? I mean, that first shape represented an amazing leap forward in transportation technology. Shouldn't there be a couple hundred million more new kinds of wheel shapes by now, at that rate?

[paximperium]

There are only so many ways to inhibit or kill bacteria. Finding a completely new way is not exactly easy.

[Dr. Trintignant]

Why should there be lots of new antibiotics?

I agree that in principle, there's no a priori reason to believe that there needs to be lots of new antibiotics. But first I'm interested in whether the claim is even true or not. So far, it sounds like it's not--there are many new antibiotics, and even the derivatives have many new properties.

I am still interested in the development of new classes of drugs, if for no other reason than to have the proper background when talking to my friend. But I agree that the answer doesn't change the fundamental point.

- Dr. Trintignant

[paximperium]

I agree that in principle, there's no a priori reason to believe that there needs to be lots of new antibiotics. But first I'm interested in whether the claim is even true or not. So far, it sounds like it's not--there are many new antibiotics, and even the derivatives have many new properties.

I am still interested in the development of new classes of drugs, if for no other reason than to have the proper background when talking to my friend. But I agree that the answer doesn't change the fundamental point.

- Dr. Trintignant
The primary issue like I mentioned are that antibiotics have to target specific biochemical or cellular characteristics only found in the bacteria. There are only so many ways to do so before the drug goes from antibiotic to chemotherapeutic drug and start attacking the host(in fact several started out as antibiotics) .

[Dr. Trintignant]

The primary issue like I mentioned are that antibiotics have to target specific biochemical or cellular characteristics only found in the bacteria. There are only so many ways to do so before the drug goes from antibiotic to chemotherapeutic drug and start attacking the host(in fact several started out as antibiotics).

Is there good reason to believe that we have found all the major biochemical characteristics already? Obviously there's a lot to still learn about cells, but I'd guess that researchers have at least some sense as to how much we've "mapped out" already. Is there a "great unknown" still, or is there not much left?

- Dr. Trintignant

[paximperium]

Is there good reason to believe that we have found all the major biochemical characteristics already? Obviously there's a lot to still learn about cells, but I'd guess that researchers have at least some sense as to how much we've "mapped out" already. Is there a "great unknown" still, or is there not much left?

- Dr. Trintignant
Joobz is a better person to answer this question than myself.

My BSc in Biology is a tad outdated. I do clinical research and not much basic science nowadays. I have little doubt there are new pathways to attack like the iron uptake process of bacteria.

[BenBurch]

Dr. Mark Crislip maintains (via his wonderful infectious diseases podcast "Puscast") that we are at the end of the antibiotic era, and that most infections will have to be dealt with by excision and amputation in the future.

Personally, I have some hope for phage therapy, but basically he is right.

Not only do the little critters evolve immunity quickly, but they share notes between different lineages such that immunity in one bacteria spreads to all varieties in record time.

[BenBurch]

Oh, and, puscast may be found here; http://www.pusware.com/

[Puppycow]

Antibiotics make money. Why wouldn't companies develop new ones?

Because they're evil and they want you be sick so they can sell you even more expensive drugs than antibiotics. :tinfoil

[Dr. Trintignant]

Not only do the little critters evolve immunity quickly, but they share notes between different lineages such that immunity in one bacteria spreads to all varieties in record time.

Something that I've wondered about: it must be somewhat inefficient metabolically to carry resistance to all these types of antibiotics. This implies to me that in the absence of the antibiotic, resistance traits will be selected out. Is it possible, then, to "rotate" the standard course of antibiotic treatments, leaving some antibiotics "fallow" at any given time, so that diseases lose their resistance over time, and therefore the antibiotic works better the next time we use it?

- Dr. Trintignant

[paximperium]

Something that I've wondered about: it must be somewhat inefficient metabolically to carry resistance to all these types of antibiotics. This implies to me that in the absence of the antibiotic, resistance traits will be selected out. Is it possible, then, to "rotate" the standard course of antibiotic treatments, leaving some antibiotics "fallow" at any given time, so that diseases lose their resistance over time, and therefore the antibiotic works better the next time we use it?

- Dr. Trintignant
Possible but impossible to monitor or control. There is some differences in antibiotic resistance between different states and countries alone.

Most Health Departments in the US have antibiotigrams which look at the most common bacteria and their resistance. This leads to changes in antibiotic usage in a given area as resistance increases. But the county over may just begin seeing a rise in that specific resistance.

[thughes]

There's a decent article about this in the July 2009 Scientific American (Squashing Superbugs).

From what I recall, its partly a matter of all the "low hanging fruit" being taken.

- Tracy

[BenBurch]

Something that I've wondered about: it must be somewhat inefficient metabolically to carry resistance to all these types of antibiotics. This implies to me that in the absence of the antibiotic, resistance traits will be selected out. Is it possible, then, to "rotate" the standard course of antibiotic treatments, leaving some antibiotics "fallow" at any given time, so that diseases lose their resistance over time, and therefore the antibiotic works better the next time we use it?

- Dr. Trintignant

I asked Dr. Crislip this very question a year or so ago, specifically whether older, disused antibiotics would some day again be usable;


It used to be that in a non anti biotic environment, resistant
strains would be at a disadvantage and die out.

That doesn't seem to be happening as much as one would like and for
some strains like the current USA 300 strain of MRSA, it appears to
have a selective advantage as it is supplanting the community
susceptible strain.

Over time other mutations can make up for the decrease in fitness that
antibiotic resistance confers, making the resistant strain more fit.
resistance is becoming more and more the norm, despite not using the
antibiotics. Bummer.

[Dr. Trintignant]

I asked Dr. Crislip this very question a year or so ago, specifically whether older, disused antibiotics would some day again be usable;

Bummer, indeed. Thanks for the info.

I listened to a couple of his Puscasts, and he mentions a similar related study, although this was regarding transmission rates of MR TB vs. ordinary TB. The resistance didn't cause much reduction in transmission rate (<10%, IIRC).

I do still wonder if resistance can be managed in some way. It just sounds like the answer will be much more complicated than rotating the antibiotics. I wonder if it's possible to produce "complementary" antibiotics, where one drug encourages resistance to itself but discourages resistance to another drug (say, by attacking a particular biochemical marker which can only be one thing or another).

- Dr. Trintignant

[joobz]

Is there good reason to believe that we have found all the major biochemical characteristics already?
That's the funny thing about the unknown. We don't know. :p

I can say that we didn't know anything about RNAi until about 20 years ago, and we are now just starting to realize its implications in medicine.
Think about that. A fundemental highly useful process in eukaryotic cells took 30+ years after the discovery of DNA to even know there was a kink in the DNA to Protein Dogma.

Next consider the genome project, and how many genes have the "Unkown" label to them. So, I think it a bit silly to think that we've Discovered ALL possible antibacterial methods. Some groups are doing exploratory directed evolution methods to develop novel antibiotics. I'm actually working on a new idea using a combination strategy to actively suppress a diversification signal that exists in P. aeruginosa. This mechanism was discovered ~1.5 years ago, and is likely to exist in other bacteria.

And I do not know who made the "only so many elements" argument. But that's like saying, "there's only 26 letter in the alphabet. How many sentence can be written?"

Don't underestimate human ingenuity.

[Dr. Trintignant]

That's the funny thing about the unknown. We don't know. :p

I had a feeling someone would call me on that :). But to make an analogy, we've known the approximate surface area of the earth for thousands of years now. But it's only until pretty recently that we've mapped out the entire area. So even though we didn't know what there was, we had a good idea of how much there was left to discover.

Of course the analogy probably doesn't hold for biology, but that's why I asked :).

I can say that we didn't know anything about RNAi until about 20 years ago, and we are now just starting to realize its implications in medicine.
Think about that. A fundemental highly useful process in eukaryotic cells took 30+ years after the discovery of DNA to even know there was a kink in the DNA to Protein Dogma.

Huh, funky. I'll have to read up on that. I see that the 2006 Nobel Prize in medicine was related to RNAi.

Next consider the genome project, and how many genes have the "Unkown" label to them. So, I think it a bit silly to think that we've Discovered ALL possible antibacterial methods. Some groups are doing exploratory directed evolution methods to develop novel antibiotics. I'm actually working on a new idea using a combination strategy to actively suppress a diversification signal that exists in P. aeruginosa. This mechanism was discovered ~1.5 years ago, and is likely to exist in other bacteria.

Very interesting; thanks.

Is it all accurate to say that some of the research has been held up due to waiting on the tools? That is to say, the low hanging fruit--penicillin et al--was picked quickly, and then there was a slump. Only recently have we had the ability to look at a whole genome, and so huge new avenues of research have opened up--but perhaps there was something of a gap from the 80's to 90's?

- Dr. Trintignant

[Dr. Trintignant]

There's a decent article about this in the July 2009 Scientific American (Squashing Superbugs).

From what I recall, its partly a matter of all the "low hanging fruit" being taken.

- Tracy

Just finished reading that online--thanks for the reference. Sounds like the approach of the last few decades (run around collecting bacteria, and see which chemicals have an effect) is running out of steam, but that there's some promise in new approaches.

I wonder if one day we'll evolve our own super-antibiotics. Take a resistant strain and use that as "competition" with an antibiotic-producing bacteria, and wait for the latter to evolve an antibiotic that breaks through the former's defenses. The competition would have to be managed to prevent it from ending too early; something like using the results of horse racing to choose which horses to breed in the future.

- Dr. Trintignant

[Dr. Imago]

Linezolid.

Throw that one at 'em.

~Dr. Imago

[Dr. Imago]

Linezolid

I.E., not a derivative, only one in its class currently available, and definitely developed and approved long after the 1970's. In other words, this medication alone completely undoes your co-worker's argument.

~Dr. Imago

[Dr. Trintignant]

I.E., not a derivative, only one in its class currently available, and definitely developed and approved long after the 1970's. In other words, this medication alone completely undoes your co-worker's argument.

~Dr. Imago

Excellent--thanks! I think the argument was already on seriously shaky ground, but that one definitely demolishes it.

Now I just have to find out where he heard the claim in the first place. I'll ask tomorrow (though I'd still put even money on it being Michael Moore).

I have to laugh a bit, though. According to the Wikipedia article, a course of Linezolid can cost thousands of dollars. That by itself disproves the claim that "there's no money in antibiotics", but I have the feeling that if I mention the point, he'll simply use it as evidence that the drug companies are greedy bastards.

Then again, as I said he is quite intelligent overall, and not the "true believer" type. So I hope I present my case well :).

- Dr. Trintignant

[Andrew Wiggin]

We've really only scratched the surface as far as taking the old standbys and combining them with ajuvant substances to overcome resistance. Amoxicillin with Clavulinate and Ampacillin with Sulbactam are examples that come to mind. It'll be a long time till we've exhausted the combinations, especially as new ways of finding out what pathway is responsible for the drug resistance and new ways of inhibiting such pathways are developed. I don't at all believe that the era of the antibiotic is over.

A

[Rolfe]

Dr. Mark Crislip maintains (via his wonderful infectious diseases podcast "Puscast") that we are at the end of the antibiotic era, and that most infections will have to be dealt with by excision and amputation in the future.

Personally, I have some hope for phage therapy, but basically he is right.

Not only do the little critters evolve immunity quickly, but they share notes between different lineages such that immunity in one bacteria spreads to all varieties in record time.


I've been hearing this since I was an undergraduate in the 1970s. At that point it was oxytetracycline that had been so overused it was allegedly next to useless. Penicillin was going the same way, and you better be bloody careful what you do with these brand-new cephalosporins.

Except - all these things are still clinically very useful. Most of the bog-standard isolates we find from common infections are sensitive to a wide range of antibiotics. Yes, there are some problem strains, and MRSA is a bummer, but in fact reports of Armageddon seem so far to be greatly exaggerated.

Rolfe.

[Cuddles]

http://en.wikipedia.org/wiki/Timeline_of_antibiotics

All that needs saying really.

Edit: Having had a look at the list, I don't think I've ever taken an antibiotic that was developed before 1981.

[rjh01]

http://en.wikipedia.org/wiki/Timeline_of_antibiotics

All that needs saying really.

Edit: Having had a look at the list, I don't think I've ever taken an antibiotic that was developed before 1981.

Interesting link. Hardly any new drugs since 1993. Yet until then most years saw several drugs released. Is that because the list is out of date or does the OP have a point (May not be 100% correct but enough to be worried)?

[Skeptic Ginger]

Why should there be lots of new antibiotics?

I mean, it's not like we're adding a lot of new elements to the periodic table. Why should there be an unlimited number of biochemical reactions that have useful medical effects against that class of biochemical systems known as "biotics"?

There's only a limited number of ways you can burn things. There's only a limited number of ways to make an acid. There's only so many variatons on the chemical compound known as "milk". Why do we have to accept, a priori, the assumption that scientists should continue to discover or invent antibiotics at a constant rate?
....There are an infinite number of ways nucleic acids can form genetic code.

Whatever toxin you subject bacteria to, so far, they evolve a way to defeat it. That is the nature of evolution.

[Skeptic Ginger]

Is there good reason to believe that we have found all the major biochemical characteristics already? Obviously there's a lot to still learn about cells, but I'd guess that researchers have at least some sense as to how much we've "mapped out" already. Is there a "great unknown" still, or is there not much left?

- Dr. TrintignantSame answer as above. It's like saying there will never be anything new to patent. It's an astoundingly limited view of the future.

[Skeptic Ginger]

Dr. Mark Crislip maintains (via his wonderful infectious diseases podcast "Puscast") that we are at the end of the antibiotic era, and that most infections will have to be dealt with by excision and amputation in the future.

Personally, I have some hope for phage therapy, but basically he is right.

Not only do the little critters evolve immunity quickly, but they share notes between different lineages such that immunity in one bacteria spreads to all varieties in record time.I'm not impressed.

The revolution in genetic science must have left Crislip in the dust. He seems unaware of the specificity of the research looking at ways to intervene in microorganism reproduction.

It used to be trial and error to find new antibiotics. Penicillin was found by accident. Later new compounds were sought out from living organisms.

Now researchers look specifically at the molecular structures and functions involved in infection and design drugs to intercede. The big problem is finding drugs which don't have major side effects. We are still at the trial and error phase of discovery in trying to find substances which can be safely given to people.

[Skeptic Ginger]

So why aren't we pumping out new antibiotics right and left? It isn't a conspiracy but there are market forces directing where Big Pharma is going to invest their R&D dollars.

Only now are we seeing enough demand from drug resistant microorganism infections to entice companies to invest in new antibiotics. Why should they tie up their capital for a small market when they can make a copycat Viagra or Lipitor and sell drugs with a known market?

You need tens of thousands of people getting infected with drug resistant strains before private enterprise is going to want to invest in the R&D to create a drug for that market.

There has been some research funded by groups concerned with our national interests. Those Libertarians and Republicans who think all we need is capitalism and the world will be wonderful don't get it. But I digress. My point is, it's not a conspiracy to make money by assuring people will stay ill. That's what you'd expect from a grade B movie plot.

It's simply a matter of prudent economic decisions by a private companies. Their goal would not be to save the world any more than it would be to consciously keep the world ill for a profit. But when you are tying up your capital in R&D, you don't do it for the long term gain of a new antibiotic which there is a guaranteed market for but not one there is a guaranteed market for in the near future. You invest in R&D of drugs that have guaranteed markets in the near future.

Also Big Pharma is going to invest more in drugs people take for a lifetime such as statins, over a drug one takes for a week or two. That doesn't mean no drugs are developed which cure people. Because a large market of a one week treatment can be as good as a smaller market of a lifetime treatment. But these market forces do tend to drive drug development to a much greater extent than human need does.

[dudalb]

Hey, all of Western Medicine is a scam to keep people ill by treating the symptoms, not the root cause.
I know this is true because Bill Maher said it on his show last week.........

[sol invictus]

Question about the evolution of antibiotic resistance in bacteria: is it obvious that increased resistance is always selected for? If a disease is too virulent, it might kill its hosts too quickly to infect many others. Therefore it might be advantageous to strike a balance at some intermediate level of virulence, and in a human host population that's routinely dosed with antibiotics that balance might involve a partial resistance to antibiotics rather than a total one.

And if the bacteria can live in environments other than humans (and the few animals that are given antibiotics), it could spread from a human host into those other environments if the antibiotic level in the human gets too toxic for it, thereby living to infect another day. If resistance involves any kind of trade-off in other selected for factors that might swing the balance against too much of it.

Perhaps the doomsday of superbugs will never come, because such bugs are actually selected against. Possible?

[Skeptic Ginger]

I'm not impressed.

The revolution in genetic science must have left Crislip in the dust. He seems unaware of the specificity of the research looking at ways to intervene in microorganism reproduction.

It used to be trial and error to find new antibiotics. Penicillin was found by accident. Later new compounds were sought out from living organisms.

Now researchers look specifically at the molecular structures and functions involved in infection and design drugs to intercede. The big problem is finding drugs which don't have major side effects. We are still at the trial and error phase of discovery in trying to find substances which can be safely given to people.I've gone back and looked at Dr C's info directly. I think you, Ben, have misconstrued his opinion. I'll follow up when I have more time.

[McHrozni]

So why aren't we pumping out new antibiotics right and left?

The cost of researching and testing a new antibiotic is approximately comparable to building and comissioning a new nuclear aircraft carrier. Do I need to point out the obvious?

McHrozni

[BenBurch]

I certainly may have misconstrued. This is not my field. I'd love to hear your interpretation.

[Skeptic Ginger]

The cost of researching and testing a new antibiotic is approximately comparable to building and comissioning a new nuclear aircraft carrier. Do I need to point out the obvious?

McHrozniDid you even bother to read my post? Maybe you should read what people write before you comment on a question they asked as a literary tool and then went on to answer in the same post.

[Skeptic Ginger]

I certainly may have misconstrued. This is not my field. I'd love to hear your interpretation.Later today I'll get back to this. I got sidetracked by a few other Bad Med blog entries and now I can't find the original one I was reading.

I'm off to do the bidding of those evil Big Pharm folks. So much flu, so little time to market vaccines. :D

[Ixion]

As a side note about resistance genes, I want to point out that many pathogenic elements of disease-causing bacteria reside in specific locations within a bacterial chromosome or extrachromasomally (on a small piece of DNA known as a plasmid). Plasmids can be easily transmitted via conjugation of bacteria or phages, but can also be lost during bacterial fission. If there is a selective agent present (such as an antibiotic), only the bugs that have the resistance gene will reproduce and thrive. Any that have lost the plasmid during fission will die. Some plasmids are good at replicating and the bacteria might have many copies of it within, making it likely to have both clones have a copy of the plasmid after fission. Low copy plasmids might result in one clone having a copy and one not having a copy, resulting in a bacteriostatic-like effect, where the total population of bacteria does not or only marginally increases. Areas of the bacterial chromosome with many pathogenic elements are known as pathogenecity islands. It must be noted that maintaining a plasmid or a pathogenecity island might be metabolically taxing to a bacteria, so it might have a tough time competing with bacteria without those elements in the absence of a selecting agent. However, I don't foresee ease of lost elements within a bacterial population without a tremendous effort to carefully monitor bacterial populations and administration of antibiotics.

Now, a couple of other things I wanted to comment on. First, I am not sure exactly what skeptigirl meant by the post There are an infinite number of ways nucleic acids can form genetic code.

I assume you meant an infinite number of ways bacteria can use nucleic acids to create proteins by linking amino acids together. If that is not what you meant, I apologize. If it is, then you are, in principle, correct. However, there are a couple of caveats that must be included in that statement. First, bacteria are limited in the amount of nucleic acids they can harbor. Spirochaete bacteria (spiral shaped) are very thin and do not adjust to excess size of their chromosomes. They do not pick up plasmids, and don't really develop antibiotic resistance. I would be foolish to say ever, but I can say with confidence that such occurences are highly unlikely to happen due to physical constraints of the bacteria. This is the reason that some diseases from spirochaete bacteria are still treated with the same antibiotics as they were decades ago (such as the treatment of syphilus with penicillin G).

Another caveat is based on metabolism. Bacteria rely on a lot of scavenging of molecules and conserving energy when possible. Although the basics of metabolism are conserved, such as fermentation and glycolysis, bacteria have only one cell to fuel and one cell to generate energy in. They are small and must dedicate a certain proportion of their total metabolic pool to creating and maintaining molecules required for generating energy or scavenging. If they do not do this, they die. This is true with higher organisms as well, but there is some sharing of resources (which is where our blood comes into play). Therefore, if a bacteria is making a long protein which uses a lot of resources, then the bacteria suffers metabolically and dies.

A quick note to Sol Invictus. The multiple ecological niches are indeed what happens with some bacteria (and viruses as well). Yersinia pestis (causes the plague) can exist in multiple mammalian hosts, with several rodent species being reservoirs that the bacteria can be maintained in without killing the host. Unfortunately, it is difficult to determine if some bacteria will jump species or not, so you can't just go and give hundreds of wild animals antibiotics to kill off all the pathogens. Likewise, some bacteria can live in the soil as spores free from any host, and thus maintain their ecological niche indefinitely that way.

[Skeptic Ginger]

.....Now, a couple of other things I wanted to comment on. First, I am not sure exactly what skeptigirl meant by the post

I assume you meant an infinite number of ways bacteria can use nucleic acids to create proteins by linking amino acids together. Yes, that is what I meant. Evolution of bacteria and viruses has resulted in at least some organisms surviving all hazards posed to them since time immimorial. What evidence is there this will not continue to occur?


..... However, there are a couple of caveats that must be included in that statement. First, bacteria are limited in the amount of nucleic acids they can harbor. Spirochaete bacteria (spiral shaped) are very thin and do not adjust to excess size of their chromosomes. They do not pick up plasmids, and don't really develop antibiotic resistance. I would be foolish to say ever, but I can say with confidence that such occurences are highly unlikely to happen due to physical constraints of the bacteria. This is the reason that some diseases from spirochaete bacteria are still treated with the same antibiotics as they were decades ago (such as the treatment of syphilus with penicillin G).This is interesting but has no impact on the statement I made or the context of the discussion.

.....Another caveat is based on metabolism. Bacteria rely on a lot of scavenging of molecules and conserving energy when possible. Although the basics of metabolism are conserved, such as fermentation and glycolysis, bacteria have only one cell to fuel and one cell to generate energy in. They are small and must dedicate a certain proportion of their total metabolic pool to creating and maintaining molecules required for generating energy or scavenging. If they do not do this, they die. This is true with higher organisms as well, but there is some sharing of resources (which is where our blood comes into play). Therefore, if a bacteria is making a long protein which uses a lot of resources, then the bacteria suffers metabolically and dies. And your point, relative to the discussion is what? Are you suggesting there is an ultimate antibiotic out there we will discover at some point? One we have already discovered? Are you suggesting we should give up as we cannot ever find another means of killing or neutralizing microorganisms? Or the microorganisms are no longer able to defeat human interventions?

Do you understand my point? ... Or not?

[Ixion]

Yes, that is what I meant. Evolution of bacteria and viruses has resulted in at least some organisms surviving all hazards posed to them since time immimorial. What evidence is there this will not continue to occur?

This is interesting but has no impact on the statement I made or the context of the discussion.

And your point, relative to the discussion is what? Are you suggesting there is an ultimate antibiotic out there we will discover at some point? One we have already discovered? Are you suggesting we should give up as we cannot ever find another means of killing or neutralizing microorganisms? Or the microorganisms are no longer able to defeat human interventions?

Do you understand my point? ... Or not?

I am sorry, you seem to really have a chip on your shoulder. I was merely pointing out that certain aspects of microbial life are not easily changed. I am not suggesting that there will be an 'ultimate antibiotic', but that researchers will likely continue to develop antibiotics targeted to bacterial systems that will be difficult for the organism to change. This is relevant to the OP because new classes of antibiotics are not as likely to be created as opposed to modifying existing ones because certain metabolic systems are well studied. It only makes sense to go after what is known to work first and exhaust those options before embarking into unknown territory (and devoting the time and money of a lot of people on an uncertain principle). That doesn't mean bacteria won't develop resistance to new antibiotics, nor will it mean that humans will wipe all pathogens off the face of the Earth.

[Dr. Trintignant]

By the way, my co-worker told me that he read the statement in BusinessWeek. Unfortunately, he didn't remember the issue or title of the article, and my searches of their site have been fruitless. They do have a number of articles on antibiotics, but none (as best I can tell) that make the claim about the '70's.

Anyway, he was receptive to my argument that things aren't quite as dire as the article made them out to be. Although the point is taken that drug companies do like drugs that they can sell over and over.

There's been some good stuff in this thread; thanks all.

- Dr. Trintignant

[McHrozni]

Did you even bother to read my post? Maybe you should read what people write before you comment on a question they asked as a literary tool and then went on to answer in the same post.

Perhaps, though I don't see what the problem is in answering the same question twice. People that typically ask this question in the first place won't normally understand your answer.

McHrozni

[Skeptic Ginger]

Perhaps, though I don't see what the problem is in answering the same question twice. People that typically ask this question in the first place won't normally understand your answer.

McHrozniI would believe you except for your, "Do I need to point out the obvious," comment and the fact my posts have all been about market forces influencing what drug companies invest their capital in.


Nice try.

[Skeptic Ginger]

.... new classes of antibiotics are not as likely to be created as opposed to modifying existing ones because certain metabolic systems are well studied. It only makes sense to go after what is known to work first and exhaust those options before embarking into unknown territory (and devoting the time and money of a lot of people on an uncertain principle). That doesn't mean bacteria won't develop resistance to new antibiotics, nor will it mean that humans will wipe all pathogens off the face of the Earth.I think our difference here is in this statement, "new classes ...not as likely to be created."

That is exactly what I disagreed with in your earlier posts and I still disagree with here. It's not a chip on my shoulder. It's a disagreement with your opinion.

I read a lot of research reports on just where the research in antibiotics is going. Despite the fact there is an insufficient amount of capital being invested in an all out offensive against drug resistant pathogens, there is an incredible array of small scale investigations into the molecular workings of microorganisms and disease processes. There is more than enough potential there for new classes of drugs to be developed.

[Skeptic Ginger]

I certainly may have misconstrued. This is not my field. I'd love to hear your interpretation.Well I'm still chuckling. I went through 2 of 'Dr Crispie's' infectious disease lectures in PPT format. I'm going to have to download his podcasts. Thanks for the link.

He's merely using humor to make his points when he talks about the end of the antibiotic era. I don't read anything there other than a little satiric cynicism.

This lecture on antibiotic resistance (http://www.pusware.com/lectures/Antibiotic%20resistance.pdf) had much of what this thread asks. Slide 42: It will only get worse. We are slowly sliding into the post antibiotic era
• There will be fewer and fewer effective antibiotics:
• only five new antibiotics in the R&D pipeline out of more than 506 drugs in development.
• By comparison, pharmaceutical companies were developing 67 new drugs for cancer, 33 for inflammation/pain, 34 for metabolic/endocrine disorders, and 32 for pulmonary disease.I'm not sure saying, "we are sliding into the post antibiotic era," was meant in a fatalistic way. I think he was merely reflecting on the current trend. And that is correct.

He also cites the same reasons I've been citing. Slide 42 has a graph of new antibiotics introduced by year. And from the next couple slides:The CID analysis found that Food and Drug Administration (FDA) approvals of new antibiotics declined 56 percent during the past 20 years (1998-2002 versus 1983-1987).
• Since 1998, only 10 new antibiotics have been approved by FDA—two of which are truly novel (i.e., have a new target of action, with no crossresistance with other antibiotics).
• In 2002, among 89 new medicines emerging on the market, none was an antibiotic.
• A growing number of companies with track records in antibiotic R&D appear to be withdrawing from this market: Aventis, Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly and Co., Procter & Gamble, Roche, and Wyeth.

Its the money
• “When it comes to annual sales potential, antibiotics don’t measure up. … A musculoskeletal drug is worth about $1.150 billion, a neuroscience treatment … $720 million, and a medicine for resistant Gram-positive cocci … only $100 million.”
• (Sellers, LJ. Pharmaceutical Executive. Dec 2003)

So. We are all going to die.

This is just Dr C's humor. And personally, I got a kick out of it.

Emerging (and re-emerging) Infections:
Its the end of the world as we know it and I feel fine (http://www.pusware.com/lectures/Emerging%20Infections.pdf)The End
• So what have we learned?
• The fan is big, spinning fast, aimed at us and we are shoveling s#$@ at it as fast as we can.
• I have little optimism based on the last 5000 years of human civilization.
• I can’t even get people to wash their hands consistently, and we have known that prevents infection for 140 years.
• we are all gonna die.While he says we are shoveling money at the problem, I don't think that is correct. And Dr C noted in the previous lecture that drug companies are not investing in anti-infectives because the profits are not there. "I can't even get people to wash their hands" is the same experience I have. It's like the germ theory didn't sink in to 9/10s of the population.

He's not saying we cannot develop new drugs. He is saying we are not investing in new drugs. Or maybe he contradicted himself on that one and hasn't thought it through. The fact he jokes about being in the National Alarmist Council (an Onion organization) makes me think he is more joking that we need to change directions but not that we can't change or the real end of antibiotics is at hand. It's an issue with market forces the Libertarians among us have yet to recognize. The market is not the best mechanism for driving all innovation. Sometimes we need investments in R&D the markets are not interested in, at least in a timely manner.

Once people are dying by the droves of drug resistant organisms, then market forces will drive innovation in new antibiotic markets. Before that time, it is public investment in health care that we need.