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The rapid emergence of pan-antibiotic-resistant bacteria - a global crisis

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  • #16
    Originally posted by tbm3fan View Post
    Speaking about the availability of drugs here is one for you. Did you know that you can walk into any pharmacy in the Philippines and ask for the antibiotic of your choice. From penicillin to azithromycin to cephalosporins all without a Rx. On the other hand walk into the Pharmacy and look for a nasal decongestant, like sudafed, you won't find it on the shelf. You need to ask the pharmacist for it and you are then informed you can only obtain it with a prescription. I'd say go figure but the "Philippines" makes it self explanatory.
    Same in India but here's the rub. The drugs need to be chosen to target the specific germs in question. When i went to the hospital recently they took a culture and the report said the germs i had were resistant to a number of drugs out there and here was a list of others that could target them more effectively.

    it's an arms race.

    When i brought this subject up with my doctor he told me there were still drugs out there that could do the job. A lot of them are actually out of patent. The trick is matching them to the germs in question.

    This does not preclude the possibility of a super bug, but its good enough for a lot of other diseases for now.

    Remember the bird flu scare and other flu's over the previous years, did not really spread too much or the effects were muted. There are a number of preventative methods that can be used to reduce the spread of these bugs.
    Last edited by Double Edge; 02 Jan 14,, 09:55.

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    • #17
      Originally posted by Double Edge View Post
      Same in India but here's the rub. The drugs need to be chosen to target the specific germs in question. When i went to the hospital recently they took a culture and the report said the germs i had were resistant to a number of drugs out there and here was a list of others that could target them more effectively.

      it's an arms race.

      When i brought this subject up with my doctor he told me there were still drugs out there that could do the job. A lot of them are actually out of patent. The trick is matching them to the germs in question.

      This does not preclude the possibility of a super bug, but its good enough for a lot of other diseases for now.

      Remember the bird flu scare and other flu's over the previous years, did not really spread too much or the effects were muted. There are a number of preventative methods that can be used to reduce the spread of these bugs.
      The problem is some of the bugs out of India now (and also the US) are resistant to everything. So far most of us have only a remote chance of encountering such bugs, but this is going to change, possibly quickly in the years ahead.
      Last edited by citanon; 02 Jan 14,, 11:18.

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      • #18
        Originally posted by Bigfella View Post
        ... are the over-prescription/over-use of antibiotics and hospitals themselves.
        I know you were referring to the overuse by humans, but the same is occuring in the food industry. The bacteria dont know the difference, so immunity evolving in either theatre has the same implications for both theatres. Its virtually the same problem. Yet we can manage animals easier than the habits of fellow humans so it should be the easier aspect to tackle. Given the amount being used in the food industry (they use alot and there are more animals than humans), there is scope that as much of the resistance is sourced from the animal pool, while acknowledging the huge amount of uncertainty.

        Originally posted by Bigfella View Post
        My point was about the way people tend to ride their hobby horses.
        Its not relevent if iam on a crusade or not. I post, your welcome to judge the merit of what I actually say, not my motivations or your perception of them.

        Originally posted by citanon View Post
        Bonehead,

        It literally costs about a billion dollars and ten years in research today to take the drug from the lab to the clinic here in the US. You have to go through three stages of clinical trials. The costs at each stage go up exponentially. You also have a very high rate of failures considering the amount of investments you have to make. Many drugs fail at stage 3. It's an incredibly expensive business to be in. The major pharmas are trying to move research out of house by buying or teaming with smaller companies, but for antibiotics, they probably still have the best efforts around. They might be able to spin off those units with enough support or veterans of that area might start a new company, but it's going to literally take billions.
        Maybe we should consider altering the red tape to make drug development easier, and accept that some risks may be worth taking to make the process cheaper and faster.

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        • #19
          They could definitely find some extra billions if they eliminated all those damn drug commercials starting with viagra and cialis to name a few. From what I understand more is spent on advertising than on research.

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          • #20
            Originally posted by tbm3fan View Post
            They could definitely find some extra billions if they eliminated all those damn drug commercials starting with viagra and cialis to name a few. From what I understand more is spent on advertising than on research.
            True. There is entirely too much drug advertising on television. I can understand the need to advertise OTC drugs, but why do they need to spend billions on costly TV ad slots for prescription drugs (with the mandatory "Please ask your Doctor about....") at the end? Shouldn't they just make sure that the Doctors are aware of their new drug, so they can prescribe it? How many people actually see these ads, and go and demand that their doctors change their current treatment to the one they saw in the great new ad on TV? Is it even advisable to do that?

            Anyway, when this problem of drug resistant bacteria crosses a certain threshold Governments across the world will have no choice but to subsidize research into new antibiotics to deal with them. I see no other option. Sooner or later, too many people are going to start dying due to these superbugs and we won't be able to ignore them anymore. Even if we drastically curtail the abuse of antibiotics now, it will only delay this eventuality not prevent it.

            And if the government has subsidized a drug's development, it can have some control over its pricing too and make sure that the big pharma cos. don't develop a new drug and price it to be out of reach of just about everybody in the developing world. So many AIDS victims in Africa and Asia would have never got the benefit of the latest ARV's if the Big Pharma cos. had had their way. Now they are making up by "evergreening" cancer drugs.
            Last edited by Firestorm; 03 Jan 14,, 01:05.

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            • #21
              Originally posted by citanon View Post
              The problem is some of the bugs out of India now (and also the US) are resistant to everything. So far most of us have only a remote chance of encountering such bugs, but this is going to change, possibly quickly in the years ahead.
              I've heard some public radio programs speak about it but i'm unsure as to how serious the problem actually is. Funding is cited as the biggest one. A lack of sufficent incentive prevents developing drugs that will generate enough profit.

              The story goes that bugs have gotten super resistant and that is because of what we did over the last half a century so we better watch out for the future. The pharma industry that has been coming out with lots of very successful drugs all of a sudden finds itself out gunned and in need of govt assistance.

              What i've not heard mentioned is what your opener says, that they need to develop the drugs and constrain their distribution. Not because of patent infringement but because they might not get another chance. That's real alarmist.

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              • #22
                Originally posted by Double Edge View Post

                What i've not heard mentioned is what your opener says, that they need to develop the drugs and constrain their distribution. Not because of patent infringement but because they might not get another chance. That's real alarmist.
                That's not really the reason for constraining supply. The reason is 2 fold:

                1. What you are fighting against here is evolution. Let's say I come out with a brand spanking new drug that kicks the ass of every superbug out there. If I let the whole world have it, and every one and his uncle starts using it in inappropriate ways, then resistance to my new drug will emerge very quickly, and I'm back to square one. Off to spend another $1-10 billion. On the other hand, if I limit distribution, these newer drugs could be potent for a very long time.

                2. What you need here is government funding for the development effort because there's no guaranteed market. There's a chance that the superresistant bugs could spread far and wide far faster than our ability to respond, and it would be an absolute catastrophe, but there's a chance that they will spread slowly, and the yearly market will be small compared to the development costs unless the drug is priced very high. However, we may see the resistant bugs in developing countries first. In this case, the high pricing won't work. Thus, there has to be a supply constraint using mechanisms other than price.

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                • #23
                  Missing the less expensive things here. Easier to prevent spread first. Encourage good sanitation both personal and in public places. Increase oversight of sanitation at Hospitals, nursing homes and rehab facilities. These are places where viruses spread. Save the super antibiotics for the elderly and weak and monitor it's use. Antibiotics do get over-prescribed, but what does the damage is that people don't complete the prescribed course or take it properly and it allows the virus to be exposed to the antibiotic without killing it. Elderly people, especially those living by themselves or with dementia frequently have problems keeping to a routine of medication. Track outbreaks and quarantine or isolate when possible. Work on these things first and the increase in mutations and spread will probably slow down, decreasing the need for large amounts of new antibiotics.

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                  • #24
                    Originally posted by citanon View Post
                    Bonehead,

                    It literally costs about a billion dollars and ten years in research today to take the drug from the lab to the clinic here in the US. You have to go through three stages of clinical trials. The costs at each stage go up exponentially. You also have a very high rate of failures considering the amount of investments you have to make. Many drugs fail at stage 3. It's an incredibly expensive business to be in. The major pharmas are trying to move research out of house by buying or teaming with smaller companies, but for antibiotics, they probably still have the best efforts around. They might be able to spin off those units with enough support or veterans of that area might start a new company, but it's going to literally take billions.
                    A couple of my old Organic Chemistry professors previously worked for pharmaceutical companies. It was quite common that research alone was not half of what the advertising, overhead and regulatory measures. Liabilities from bad reactions to compounds were also a fast rising cost. Sometimes the compounds were over researched as when they found something that worked they also did parallel/consecutive research on compounds that were tweaked a bit more or less just to make sure they had the better compound overall. That added time and money when literally any of the successful compounds would have worked. Other breakthroughs were quietly shelved because the company didn't think they could make enough money selling it. These guys brought scores of examples to back up their assertions and they personally worked on many of the examples they spoke of. Another reason research was higher than it needed to be as that limited competition. You needed to be a big player in the industry or you simply could not afford to see your wonder drug to the market. The bottom line is that we need to lower the cost to bring vital medicines like antibiotics to market and we need to stop with our current M.O. which is "do whatever and they will make a pill to correct all your mistakes".
                    Removing a single turd from the cesspool doesn't make any difference.

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                    • #25
                      Originally posted by citanon View Post
                      That's not really the reason for constraining supply. The reason is 2 fold:

                      1. What you are fighting against here is evolution. Let's say I come out with a brand spanking new drug that kicks the ass of every superbug out there. If I let the whole world have it, and every one and his uncle starts using it in inappropriate ways, then resistance to my new drug will emerge very quickly, and I'm back to square one. Off to spend another $1-10 billion. On the other hand, if I limit distribution, these newer drugs could be potent for a very long time.
                      Translation : existing patent laws aren't doing enough to protect our bottom line. We need to complement with a scientific sounding rationale.

                      Originally posted by citanon View Post
                      2. What you need here is government funding for the development effort because there's no guaranteed market. There's a chance that the superresistant bugs could spread far and wide far faster than our ability to respond, and it would be an absolute catastrophe, but there's a chance that they will spread slowly, and the yearly market will be small compared to the development costs unless the drug is priced very high. However, we may see the resistant bugs in developing countries first. In this case, the high pricing won't work. Thus, there has to be a supply constraint using mechanisms other than price.
                      We don't want to do more development unless the govt funds it and we are going to create this scare story in order to achieve our ends

                      Granted there are elements of truth to the story here, i'm just not buying the potentially civilisation ending punch line.
                      Last edited by Double Edge; 03 Jan 14,, 13:10.

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                      • #26
                        Originally posted by Double Edge View Post
                        Translation : existing patent laws aren't doing enough to protect our bottom line. We need to complement with a scientific sounding rationale.


                        We don't want to do more development unless the govt funds it and we are going to create this scare story in order to achieve our ends

                        Granted there are elements of truth to the story here, i'm just not buying the potentially civilisation ending punch line.


                        No risk of civilization ending, but we are looking at a lot more people having "mass die-offs" from basic food poisoning to small outbreaks. It would be kind of tough to watch one or all of your children die of a basic infection that could have been cured a few years earlier with a shot.
                        Removing a single turd from the cesspool doesn't make any difference.

                        Comment


                        • #27
                          Watching the pbs episode, it says US only but streamed fine for me.

                          Originally posted by bonehead View Post
                          No risk of civilization ending, but we are looking at a lot more people having "mass die-offs" from basic food poisoning to small outbreaks.
                          Bugs that cause 'mass die-offs' are self-limiting. To be successful and spread they need to make their hosts sick and then survive treatment in order to spread to others. However this is more true for virus than bacteria that do not need a host to survive. Bacteria can survive as spores on their own indefinitely.

                          Originally posted by bonehead View Post
                          It would be kind of tough to watch one or all of your children die of a basic infection that could have been cured a few years earlier with a shot.
                          It's possible but how likely are you to end up like that 11 yr old who caught something on the playground. Kids are the best germ laboratories out there. It is estimated that 2 million people per year get infected of which 23k died. One in a hundred. What happens to that 1 in a hundred is not good.

                          NDM-1 is the culprit. Highly resistant gram negative bugs. The present method is to operate infected areas when possible to prevent further infection. The scary point is these bugs can transfer their anti-biotic resistance to other bugs.

                          KPC is another. Spread by contact. The story about the Seattle hospital with the outbreak. This outbreak subsides later as suddenly as it began. Why ? Better containment.

                          The one thing that does not surprise me is these hospital transmitted bugs. Go to the hospital to fix one thing and catch something another. Had a cousin pick up pneumonia when being treated for something else. So he ended up staying little longer but came out ok.

                          The point is made, the more you use antibiotics, the more they lose their effectiveness. In the sense you develop an immunity to them and if you need them later then other anti-biotics are required. In the UK, the use of antibiotics is proscribed, to the point that its a dogma to use them unless absolutely essential. Elsewhere (US & France) liberal use is made because they are very effective and can knock out an infection much sooner and more thoroughly than otherwise. What i noticed with my doctor is he tends to rotate them, that is to say, after a few days he switches to something else rather than continue the same drugs. This way you reduce the chances of building immunity and still benefit. 1-2 weeks tops.

                          Do not underestimate the market for these drugs, if the need arises the problem fixes itself, companies then decide that it actually now makes sense to develop them. Right now it might not, this is why they are closing down their antibiotics research divisions. They're not profitable. So let more cases arise and the investors will not oppose further development :)

                          A study by the Frontline correspondent of NIH research priorities indicates anti-microbial resistance as #70 on the list. There are 69 other more pressing issues than this for NIH. No wonder Pfizer which was a leader in developing penicillin and led the field in antibiotics research closed down its Groton antibiotics branch.
                          Last edited by Double Edge; 04 Jan 14,, 17:23.

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                          • #28
                            [QUOTE=Double Edge;946225]Watching the pbs episode, it says US only but streamed fine for me.


                            Bugs that cause 'mass die-offs' are self-limiting. To be successful and spread they need to make their hosts sick and then survive treatment in order to spread to others. However this is more true for virus than bacteria that do not need a host to survive. Bacteria can survive as spores on their own indefinitely.



                            TB Is one such bacteria that is primed to return. It would make AIDS look like a walk in the park. More like another plague. Just imagine the death counts if the plague returned and we had nothing to combat it? Even every day resistant bacteria will kill when allowed to spread among those with weak immune systems. The death counts won't be as remarkable at first but in time will add up. Kids will get hit the worst as their lack of understanding of hygiene is what eventually kills them. Many get infected but few die because we still have the medicine to save. In less developed countries children are dying regularly for a simple lack of antibiotics.


                            The one thing that does not surprise me is these hospital transmitted bugs. Go to the hospital to fix one thing and catch something another. Had a cousin pick up pneumonia when being treated for something else. So he ended up staying little longer but came out ok.
                            This day and age you have to feel lucky or be on deaths door step to enter a hospital. You know that is where the sick people congregate and aside from specific isolation areas the HVAC system blows all the germs around over and over in the general areas. Even the operating rooms are not all that clean.


                            The point is made, the more you use antibiotics, the more they lose their effectiveness. In the sense you develop an immunity to them and if you need them later then other anti-biotics are required. In the UK, the use of antibiotics is proscribed, to the point that its a dogma to use them unless absolutely essential. Elsewhere (US & France) liberal use is made because they are very effective and can knock out an infection much sooner and more thoroughly than otherwise. What i noticed with my doctor is he tends to rotate them, that is to say, after a few days he switches to something else rather than continue the same drugs. This way you reduce the chances of building immunity and still benefit. 1-2 weeks tops.


                            It is not so much that YOU develop an immunity but the bacteria inside you that develops an immunity. I am not sure rotating after a couple of days as not all the bacteria is dead by then and whatever survives can be resistant to what you used "yesterday" I think it would be better to stay the course and wait until the next infection to use something else. The protocols could be different for those fighting for their lives and on long term antibiotics. I haven't been down that road so I don't know.


                            Do not underestimate the market for these drugs, if the need arises the problem fixes itself, companies then decide that it actually now makes sense to develop them. Right now it might not, this is why they are closing down their antibiotics research divisions. They're not profitable. So let more cases arise and the investors will not oppose further development :)

                            A study by the Frontline correspondent of NIH research priorities indicates anti-microbial resistance as #70 on the list. There are 69 other more pressing issues than this for NIH. No wonder Pfizer which was a leader in developing penicillin and led the field in antibiotics research closed down its Groton antibiotics branch.


                            So what you are saying is that only after a certain number of people die needlessly companies will begin looking to develop a new medicine. Kind of sucks for those thrown under the bus. I believe life is a pretty basic right. If there is something I can take, a mouthful of dandelions for instance, to cure the infection I believe I should have the right to that information. The pharmaceutical companies differ. They are more concerned about their profits and putting me in a position to buy their product or die. I don't like the idea of a company pining for me to get sick so they can profit from it. There is something fundamentally wrong with that.
                            Removing a single turd from the cesspool doesn't make any difference.

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                            • #29
                              Originally posted by bonehead View Post
                              TB Is one such bacteria that is primed to return. It would make AIDS look like a walk in the park. More like another plague. Just imagine the death counts if the plague returned and we had nothing to combat it? Even every day resistant bacteria will kill when allowed to spread among those with weak immune systems. The death counts won't be as remarkable at first but in time will add up. Kids will get hit the worst as their lack of understanding of hygiene is what eventually kills them. Many get infected but few die because we still have the medicine to save. In less developed countries children are dying regularly for a simple lack of antibiotics.
                              AIDS was lethal in the 80s and early 90s. By the 2000s it was survivable. A kid born to an AIDS infected mother did not get AIDS.

                              How likely is a TB outbreak. How bad will it be. How much money can be made by treating it. If the sign are there and the $$s certain then we'll manage fine. The ones that get it early will be lost. That's the way it goes.

                              Originally posted by bonehead View Post
                              It is not so much that YOU develop an immunity but the bacteria inside you that develops an immunity. I am not sure rotating after a couple of days as not all the bacteria is dead by then and whatever survives can be resistant to what you used "yesterday" I think it would be better to stay the course and wait until the next infection to use something else. The protocols could be different for those fighting for their lives and on long term antibiotics. I haven't been down that road so I don't know.
                              Your chances presently of catching those bacteria are 1 in a hundred. Now that i think of it the reason my doctor rotated the drugs was to examine whether they were effective. An examination three days later would confirm whether another more effective drug was required. The course is maintained until he told me to stop.

                              Long term antibiotics is another ball game entirely. These people are the most vulnerable with resistant bacteria.


                              Originally posted by bonehead View Post
                              So what you are saying is that only after a certain number of people die needlessly companies will begin looking to develop a new medicine. Kind of sucks for those thrown under the bus. I believe life is a pretty basic right. If there is something I can take, a mouthful of dandelions for instance, to cure the infection I believe I should have the right to that information. The pharmaceutical companies differ. They are more concerned about their profits and putting me in a position to buy their product or die. I don't like the idea of a company pining for me to get sick so they can profit from it. There is something fundamentally wrong with that.
                              Yes but then why is NIH saying their priority for anti-microbial resistance is #70 ?

                              What do the NIH #1-#10 list of priorites say is what i'd be more concerned about.

                              This is a govt org. Because there are other more threatening issues out there presently. Its a triage of priorities.
                              Last edited by Double Edge; 05 Jan 14,, 18:08.

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                              • #30
                                Originally posted by Double Edge View Post
                                A

                                Yes but then why is NIH saying their priority for anti-microbial resistance is #70 ?
                                Because they have not yet managed to pull their bureaucratic heads out of their asses. Actually I think many of the bureaucrats and certainly many of the experts have already realized the problem, but bureaucracy itself moves at another pace.

                                You can ask the same question of the Russian or Chinese ice breakers that got stuck in the Antarctic. Why did they get stuck? Because the ice moved faster than their decision and reaction cycle.

                                This bacterial resistance issue is showing signs of moving faster than our market economics - research - approval cyle. We do not want that to happen here.

                                What do the NIH #1-#10 list of priorites say is what i'd be more concerned about.

                                This is a govt org. Because there are other more threatening issues out there presently. Its a triage of priorities.
                                The NIH is concerned with issues of public health. That means things like obesity will be higher priority for the moment. However, what scares people about this problem is the growth potential. You will not have pandemic Diabetes that grows 1000% in affected number of patients over the course of a few years. You could well have with this.

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