Resistant Infections in Hospitals

[Rob Lister]

In this thread, there was a somewhat off-topic discussion about doctor's over-prescribing antibiotics and how that causes the pathogens to become resistant to them. Barbrae posted a lengthy quote from WHO (but does not post a link) which states:

"About 14,000 people are infected and die each year as a result of drug-resistant microbes picked up in U.S. hospitals, WHO reported. Globally, WHO said drug-resistant bacteria account for up to 60 percent of hospital-acquired infections."

I'm curious about this. What else should you expect? This seems like a very biased sample from which to draw a conclusion or make an example.

Person gets infection.
Person goes to doctor.
Doctor prescribes antibiotic.
Infection goes away
End of problem.

Or!

Infection doesn't go away/gets worse.
Person goes to doctor.
Doctor check person into hospital.

So the only (well, not the only) people getting admitted to the hospital are those that have infections that standard antibiotics can't handle.

Even granting that some people wait until infections are already life-threaten before seeing a doctor and that some infections are picked up in the hospital itself it still amazes me that the number isn't higher than 60%.

To me, it only illustrates that if you pick something up in a hospital it is much more likely to be a very nasty something indeed.

You guys and gals set me straight here. I don't claim to know much about this.

 

[Dymanic]

The assumption I question is this:

Infection doesn't go away/gets worse.
Person goes to doctor.
Doctor check person into hospital.

So the only (well, not the only) people getting admitted to the hospital are those that have infections that standard antibiotics can't handle.

By definition, nosocomial infection refers to an infection aquired while the patient was in the hospital.

 

[Rob Lister]

The assumption I question is this:
By definition, nosocomial infection refers to an infection aquired while the patient was in the hospital.

You'll have to elaborate was to why you question the assumption. That was the point I was trying to make: a far greater majority of infections you might run across in a hospital are, because of the nature of who goes to hospitals, resistant to standard antibiotics. If they weren't, the patient that spreads the infection wouldn't be there in the first place (assuming he was there for an infection, of course).

 

[Dymanic]

Originally posted by Rob Lister
You'll have to elaborate was to why you question the assumption. That was the point I was trying to make: a far greater majority of infections you might run across in a hospital are, because of the nature of who goes to hospitals, resistant to standard antibiotics. If they weren't, the patient that spreads the infection wouldn't be there in the first place (assuming he was there for an infection, of course).

That last sentence contains the assumption I'm questioning: that the patient had the infection when he went to the hospital; i.e., that at some point, some patient had an infection from a antiboitic resistant strain, and that patient imported it into the hospital environment. I'm not saying that couldn't possibly be the case, simply that assuming so overlooks another possibility, which is that resistance in some strains of pathogens may be largely products of the hospital environment, where the ubiquitous presence of antibiotics means that only resistant strains have a chance (and, indirectly, of the economics involved in running a hospital). Many patients in a hospital -- whose reasons for being there are not due to infection, such as surgical patients -- are given antibiotics prophylactically; in addition, even when infection is present, the appplication of broad-spectrum antibiotics is often regarded as more cost effective than culturing.

 

[Rob Lister]

That last sentence contains the assumption I'm questioning: that the patient had the infection when he went to the hospital; i.e., that at some point, some patient had an infection from a antiboitic resistant strain, and that patient imported it into the hospital environment. I'm not saying that couldn't possibly be the case, simply that assuming so overlooks another possibility, which is that resistance in some strains of pathogens may be largely products of the hospital environment, where the ubiquitous presence of antibiotics means that only resistant strains have a chance (and, indirectly, of the economics involved in running a hospital). Many patients in a hospital -- whose reasons for being there are not due to infection, such as surgical patients -- are given antibiotics prophylactically; in addition, even when infection is present, the appplication of broad-spectrum antibiotics is often regarded as more cost effective than culturing.

I think I understand your contention but I still don't understand if it can be used to wholly dismiss my secondary point: using hospital's as an example of why over-perscription is bad is a bad example to use. Plus, as I brought up in the other thread, prophylactic use cannot result in resistance unless there the pathogen that becomes resistant is present in the patient in the first place, thus making such use indicated.

Not explained well but I'm lazy. Plus I'm probably dead-ass wrong. Anyway, read into that what I mean to write. Tx.

 

[Dymanic]

Originally posted by
I think I understand your contention but I still don't understand if it can be used to wholly dismiss my secondary point: using hospital's as an example of why over-perscription is bad is a bad example to use.

I think I understand your objection as well, but I doubt if that's where the WHO was coming from anyway, since it would be vastly oversimplifying the problem to attribute it to: 'overprescription'.

Suppose for the moment that we could ignore as factors the expectations placed upon health-care providers by a public largely ignorant of the biology involved (as well as their unreliability as responsible users of antibiotics as outpatients), and also the increasing demands from society at large for cost-effectiveness in health care (while we're at it, let's pretend we could ignore any influence drug companies might have in promoting their products).

What is the best overall policy regarding the use of antibiotics (antimicrobials, actually)? Resistance has already rendered many once-effective drugs virtually useless, and we have learned to expect to see increasing resistance to every new one we introduce. Do we go ahead and put every newly developed drug into widespread use? If so, we are gambling the futures of millions on our ability to continue to develop new ones. Do we hold off, squeeze the last bit of usefulness out of every old drug before abandoning it? Many thousands at least would certainly die right away.

Anybody up for a twenty-year, world-wide moratorium on the use of antimicrobial agents? That could buy (some of) us some time, but it might be tricky to enforce.

 

[jambo372]

The reason an infection caught in a hospital is more likely to be resistant to drugs is quite simple, lots of infections occur in hospitals because lots of people with infections come in for treatment, infection can take advantage of people undergoing surgery, people with conditions such as cancer and AIDS, people on chemotherapy and immunosuppressant medications. Lots of infections and people with risk factors for infection in the hospital creates an ideal environment for spread of infection. Many people in hospital for infections will receive at least one antibiotic. Patients may also take prophylactic antibiotics following surgical procedures. The constant heavy use of various different antibiotics selects for resistant strains throughout the hospital which patients may pick up.

The percentage of infections which are drug resistant isn't 60% in all hospitals. It varies from area to area. Some countries are coping comparatively well with superinfection in hospitals eg Holland, Scandinavian countries & Canada. Other countries have very poor records in regards to this eg Japan, the USA, southern Europe and third world countries.

If antibiotics are used resistance cannot be stopped completely but can be greatly slowed down.

The main problem is idiot doctors prescribing antibiotics for common problems where they aren't required eg colds, flu, oher viral conditions and minor self limiting bacterial infections.
Doctors do this either because they have mistaken the etiology of infection or because they want to impress a demanding patient/placebo effect.
Dirty hospitals with poor infection control are also problematic.

Another cause of abnormally high resistance is when the type of antibiotic used is incorrect. Doctors are urged to prescribe narrow spectrum antibiotics whenever practical ie drugs active against only a few specific organisms. These drugs select for fewer mutants.

All bacteria can become resistant to drugs but some are more likely to than others. The most famous of these is Staphylococcus aureus but there are several others as follows :
Staphylococcus epidermis
Streptococcus pneumoniae ( Pneumococcus )
Neisseria Gonorrhoeae ( Gonococcus )
Pseudomonas aeruginosa
Enterobacter
Acinetobacter
Citrobacter
Klebsiella ( Friedlander's bacillus )
Shigellae ( Dysentery bacilli )
E.coli
Salmonellae
Proteus mirabilis
Mycobacterium tuberculosis
Enterococcus
Clostridium difficile ... and several others.

Different bacteria use different tricks to outwit different drugs. There are several different ways bacteria have done this.
eg To survive the effect of an antibiotic the bacteria may produce an enzyme which denatures the drug, this is a common mechanism of resistance to several different drugs including Penicillins, many such enzymes exist today some of which inactivate multiple closely related drugs. Other bacteria resist Penicillins and related drugs by changing proteins in their cell walls so that the antibiotic can no longer bind to and lyse the cell effectively, this is the principal resistance mechanism present in MRSA.

Several bacteria have another mechanism of resistance known as a drug efflux pump which transport certain antibiotics such as Tetracycline out of the bacterial cell before they have the chance to accumulate in toxic levels harmful to the bacterial cell.

Resistance to many drugs has occured as a result of change to the bacterial ribosomes.

Another mechanism of resistance is acheived by the alteration of the cell membrane, making the cell impermeable to the antibiotic.

An annoying feature is that resistance can spread from species to species via genetic transfer on a plasmid or transposon. This means that bacteria can spread their resistance to previously sensitive bacteria of a different species. The most frightening feature of this is transmission of R - plasmids which carry genetic information encoding for resistance to several unrelated antibiotics.

Also, it is no longer a case of the select few organisms resistant to 'common' or 'standard' drugs. Certain organisms are now resistant to all currently licensed drugs or at least most of them. A significant proportion of MRSA for instance, can be treated only with Vancomycin/Teicoplanin, 2 very toxic restricted use drugs which have to be given IV in hospital. Some newly introduced drugs have also shown effect. Some Enterococci and Pseudomonas can only be treated with experimental medications, if anything.

Many resistant infections are now showing in the community, outside hospitals including an abnormally virulent strain of MRSA that produces a potent toxin known as Panton Valentine Leukocidin. Strains of Pneumococci resistant to most of the standard medications have often caused middle ear infection, pneumonia, sinusitis, bronchitis, septicaemia and meningitis outside hospitals especially in children and the elderly. Most of the serious superinfections however are nosocomial in origin.

 

[Rob Lister]

The reason an infection caught in a hospital is more likely to be resistant to drugs is quite simple, lots of infections occur in hospitals because lots of people with infections come in for treatment, infection can take advantage of people undergoing surgery, people with conditions such as cancer and AIDS, people on chemotherapy and immunosuppressant medications. Lots of infections and people with risk factors for infection in the hospital creates an ideal environment for spread of infection. Many people in hospital for infections will receive at least one antibiotic. Patients may also take prophylactic antibiotics following surgical procedures. The constant heavy use of various different antibiotics selects for resistant strains throughout the hospital which patients may pick up.

The percentage of infections which are drug resistant isn't 60% in all hospitals. It varies from area to area. Some countries are coping comparatively well with superinfection in hospitals eg Holland, Scandinavian countries & Canada. Other countries have very poor records in regards to this eg Japan, the USA, southern Europe and third world countries.

If antibiotics are used resistance cannot be stopped completely but can be greatly slowed down.

The main problem is idiot doctors prescribing antibiotics for common problems where they aren't required eg colds, flu, oher viral conditions and minor self limiting bacterial infections.
Doctors do this either because they have mistaken the etiology of infection or because they want to impress a demanding patient/placebo effect.
Dirty hospitals with poor infection control are also problematic.

Another cause of abnormally high resistance is when the type of antibiotic used is incorrect. Doctors are urged to prescribe narrow spectrum antibiotics whenever practical ie drugs active against only a few specific organisms. These drugs select for fewer mutants.

All bacteria can become resistant to drugs but some are more likely to than others. The most famous of these is Staphylococcus aureus but there are several others as follows :
Staphylococcus epidermis
Streptococcus pneumoniae ( Pneumococcus )
Neisseria Gonorrhoeae ( Gonococcus )
Pseudomonas aeruginosa
Enterobacter
Acinetobacter
Citrobacter
Klebsiella ( Friedlander's bacillus )
Shigellae ( Dysentery bacilli )
E.coli
Salmonellae
Proteus mirabilis
Mycobacterium tuberculosis
Enterococcus
Clostridium difficile ... and several others.

Different bacteria use different tricks to outwit different drugs. There are several different ways bacteria have done this.
eg To survive the effect of an antibiotic the bacteria may produce an enzyme which denatures the drug, this is a common mechanism of resistance to several different drugs including Penicillins, many such enzymes exist today some of which inactivate multiple closely related drugs. Other bacteria resist Penicillins and related drugs by changing proteins in their cell walls so that the antibiotic can no longer bind to and lyse the cell effectively, this is the principal resistance mechanism present in MRSA.

Several bacteria have another mechanism of resistance known as a drug efflux pump which transport certain antibiotics such as Tetracycline out of the bacterial cell before they have the chance to accumulate in toxic levels harmful to the bacterial cell.

Resistance to many drugs has occured as a result of change to the bacterial ribosomes.

Another mechanism of resistance is acheived by the alteration of the cell membrane, making the cell impermeable to the antibiotic.

An annoying feature is that resistance can spread from species to species via genetic transfer on a plasmid or transposon. This means that bacteria can spread their resistance to previously sensitive bacteria of a different species. The most frightening feature of this is transmission of R - plasmids which carry genetic information encoding for resistance to several unrelated antibiotics.

Also, it is no longer a case of the select few organisms resistant to 'common' or 'standard' drugs. Certain organisms are now resistant to all currently licensed drugs or at least most of them. A significant proportion of MRSA for instance, can be treated only with Vancomycin/Teicoplanin, 2 very toxic restricted use drugs which have to be given IV in hospital. Some newly introduced drugs have also shown effect. Some Enterococci and Pseudomonas can only be treated with experimental medications, if anything.

Many resistant infections are now showing in the community, outside hospitals including an abnormally virulent strain of MRSA that produces a potent toxin known as Panton Valentine Leukocidin. Strains of Pneumococci resistant to most of the standard medications have often caused middle ear infection, pneumonia, sinusitis, bronchitis, septicaemia and meningitis outside hospitals especially in children and the elderly. Most of the serious superinfections however are nosocomial in origin.

Quoted simply because it deserved to be.

What a great post/explaination in novice terms. It answered all my questions and cleared up quite a few misgivings and misunderstandings.

If there were a salute icon, I'd use it.

 

[jambo372]

I think I understand your objection as well, but I doubt if that's where the WHO was coming from anyway, since it would be vastly oversimplifying the problem to attribute it to: 'overprescription'.

Suppose for the moment that we could ignore as factors the expectations placed upon health-care providers by a public largely ignorant of the biology involved (as well as their unreliability as responsible users of antibiotics as outpatients), and also the increasing demands from society at large for cost-effectiveness in health care (while we're at it, let's pretend we could ignore any influence drug companies might have in promoting their products).

What is the best overall policy regarding the use of antibiotics (antimicrobials, actually)? Resistance has already rendered many once-effective drugs virtually useless, and we have learned to expect to see increasing resistance to every new one we introduce. Do we go ahead and put every newly developed drug into widespread use? If so, we are gambling the futures of millions on our ability to continue to develop new ones. Do we hold off, squeeze the last bit of usefulness out of every old drug before abandoning it? Many thousands at least would certainly die right away.

Anybody up for a twenty-year, world-wide moratorium on the use of antimicrobial agents? That could buy (some of) us some time, but it might be tricky to enforce.

Doctors are now trying to 'cycle' drugs. The idea behind it is that as soon as the bacteria are ready to resist your current drug of choice, you change to a completely different drug and hence put the bacteria back to square one.

Doctors have also tried using combination therapy with multiple drugs to reduce the chance of resistance developing during therapy. This practice has been used for years in treating TB.

Studies have found that bacteria often lose resistance over time and certain bacteria are now regaining sensitivity to some of the older drugs as they develop resistance to newer ones.

Microbiologists and Biochemists are trying to find new antibiotics in nature and develop new synthetic antibacterials.
Some Microbiologists fear we may run out of antibiotics as they have found far fewer in recent decades than before.

Additionally, most of the antibiotics we already have came from a few specific sources. Roughly 60 % of all our current antibiotics can be traced backed to soil dwelling bacteria of the genus Streptomyces alone . Most others have also came from related bacteria such as Amycolatopsis. A few have also came from moulds and these have several derivatives.

Resistance to most of the new drugs is expected to occur quickly as they aren't brand new per se. They are mostly semisynthetic analogues of existing antibiotics. Some new drugs however have been found in algae and certain bacteria.

Vaccines are another key approach. Scientists are currently researching various vaccines for resistant infections.

Scientists are also investigating traditional treatments such as phage therapy and certain herbal remedies.

 

[Dymanic]

I see this as a classic example of "the tragedy of the commons". If corporations could make their own long-term interests as well as social and environmental responsibility their first priority -- and still operate profitably -- then everyone would gain. But they can't, because they have to compete in an environment in which no one else does that.

The WHO can 'urge doctors to prescribe narrow spectrum antibiotics whenever practical' all they want, but if the same doctors are also being urged by their employers to get the maximum number of patients out the door in the minimum amount of time, then for most of those doctors, it simply isn't. This is an artifact of a system which makes health care a for-profit activity, conducted in an environment in which the winners are those with the most effective strategies for short-term self-interest.

Whataya gonna do, eh?

 

[Anders]

The reason an infection caught in a hospital is more likely to be resistant to drugs is quite simple, lots of infections occur in
< snip >

I'm going to print this and put it on my fridge door. It's the best summary of the antibiotics resistance problem I've seen!

You should write books, Jambo!

 

[Anders]

I see this as a classic example of "the tragedy of the commons". If corporations could make their own long-term interests as well as social and environmental responsibility their first priority -- and still operate profitably -- then everyone would gain. But they can't, because they have to compete in an environment in which no one else does that.

The WHO can 'urge doctors to prescribe narrow spectrum antibiotics whenever practical' all they want, but if the same doctors are also being urged by their employers to get the maximum number of patients out the door in the minimum amount of time, then for most of those doctors, it simply isn't. This is an artifact of a system which makes health care a for-profit activity, conducted in an environment in which the winners are those with the most effective strategies for short-term self-interest.

Whataya gonna do, eh?

I don't agree. Firstly, quite few corporations do take their responsibility towards mankind, the environment, and so forth. Corporations are generally not the 'evil mega corps' that some lefties seem to want them to be. Big Pharma are big because developing medical drugs is not that cheap. And also there are load of small pharma as well.

But the issue about antibiotic prescription is probably more linked to education. MDs are not more intelligent or more keen on reading up on the latest medical discoveries then any other person. There are probably loads of doctors that never come in contact with any resistance problems, so they believe that prescribe any antibiotic is quite a nice way to get rid of the disease. The problems arise when the patient is admitted the hospital. There are MDs out there that seem to believe that prophylactic antibiotic treatment would do any good. Prophylactic use of antibiotic should only be used in very rare cases, like before rectum surgery. We really don’t want our friend E.coli in any other place then the rectum.

 

[Badly Shaved Monkey]

Perhaps it might be appropriate to ask a follow-up question to which I have never received or found a satisfactory answer.

If exposure of a population of bacteria to antibiotics stops will the resistance wane, and if so what drives that reduction in resistance. I've seen arguments that maintenance of antibiotic resistance imposes no costs on an organism and so saving that maintenance cost would not underlie a reduction of resistance. But saying that maintaining resistance imposes no costs at all seems to defy common sense. Surely it must cost an organism something to carry around and replicate chunks of redundant genetic material.

 

[Anders]

Perhaps it might be appropriate to ask a follow-up question to which I have never received or found a satisfactory answer.

If exposure of a population of bacteria to antibiotics stops will the resistance wane, and if so what drives that reduction in resistance. I've seen arguments that maintenance of antibiotic resistance imposes no costs on an organism and so saving that maintenance cost would not underlie a reduction of resistance. But saying that maintaining resistance imposes no costs at all seems to defy common sense. Surely it must cost an organism something to carry around and replicate chunks of redundant genetic material.

As Jambo pointed out, genes for resitance are usually hold in plasmids. If you look to the amount of genetic material in an organism it is about 3.1% of the total dry weight. A couple of genes extra won't change that, expect in like the third decimal.

If the plasmids do not contain resitance genes they will contain genes something else. The microbe has no clue about what the plasmid it takes up contains. It could be genes for making it green or making it resistant to antibiotical. Again, it does not care.

So energy, ATP, used, is almost constant, restitence or green genes.

 

[Badly Shaved Monkey]

As Jambo pointed out, genes for resitance are usually hold in plasmids. If you look to the amount of genetic material in an organism it is about 3.1% of the total dry weight. A couple of genes extra won't change that, expect in like the third decimal.

If the plasmids do not contain resitance genes they will contain genes something else. The microbe has no clue about what the plasmid it takes up contains. It could be genes for making it green or making it resistant to antibiotical. Again, it does not care.

So energy, ATP, used, is almost constant, restitence or green genes.

But,

1. Small is not the same as zero. So, how small does it need to be to be irrelevant?

2. If the maintenance costs are as close to zero as makes no matter over realistic time scales I still haven't got an answer to whether resistance wanes and if so, how.

 

[Dymanic]

Originally posted by Anders
I don't agree. Firstly, quite few corporations do take their responsibility towards mankind, the environment, and so forth. Corporations are generally not the 'evil mega corps' that some lefties seem to want them to be.

You might want to have a read of Albert J. Dunlap's book: Mean Business: How I Saved Bad Companies and Make Good Companies Great, in which ol' "Chainsaw Al" describes his "viewpoints on management and the need for the person at the top to put the owners of the company first. Investors who buy stock in a firm are placing their trust in the CEO to run it in a manner that will give them a positive return on their investment. This runs counter to the current thinking of some managers, who try to think about all of a firm's stakeholders--customers, employees, suppliers, other creditors, and so on--and their impact on the future of the company."

This issue isn't about left and right, it's about game theory. I'm not saying there aren't corporations that don't try to make social and environmental responsibility their first priority -- just that there aren't any who are able to do so and remain competitive. The long and short of it is that combating resistance is expensive.

 

[Rolfe]

I'll just go off and have another little boggle that every time we find a new antibiotic, pretty much on cue, something comes up with a gene that nixes it. This doesn't happen fast enough for us to conclude that the gene was there anyway, and we've just selected for the individuals carrying it (like the moths and the melanism story), so it must be new mutations. But after all these squillions of years not needing such genes, the bugs always seem to find them when they need them. Which suggests that potentially useful (to the bacteria) resistance genes must be cropping up de novo all the time, and have been for millennia. Only once we've invented penicillin does the penicillinase gene finally get selected for.

It does look, on the face of it, rather as if the bacteria are mutating purposefully in the face of the challenge. But according to current theory, this does not happen. I can't help feeling that if we understood better how this happens, we'd understand evolution in general somewhat better.

Rolfe.

 

[jambo372]

Perhaps it might be appropriate to ask a follow-up question to which I have never received or found a satisfactory answer.

If exposure of a population of bacteria to antibiotics stops will the resistance wane, and if so what drives that reduction in resistance. I've seen arguments that maintenance of antibiotic resistance imposes no costs on an organism and so saving that maintenance cost would not underlie a reduction of resistance. But saying that maintaining resistance imposes no costs at all seems to defy common sense. Surely it must cost an organism something to carry around and replicate chunks of redundant genetic material.

Resistance can wane in the absence of the antibiotic but usually only very slowly. Some plasmids carrying resistance genes aren't very stable.

Recently this wane in resistance has been important medically.

 

[Rolfe]

Jambo, how come you come up with such excellent medical information, and still believe all that woo stuff?

Just asking....

Rolfe.

 

[jambo372]

Jambo, how come you come up with such excellent medical information, and still believe all that woo stuff?

Just asking....

Rolfe.

I'm just interested in microbiology, especially the it's medical applications.