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Old 09-17-2015, 13:41   #1
Trapper John
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Alarming Rise in Antibiotic Resistance

From the most recent FierceHealthcare report -

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Antibiotic resistance: Global report reveals alarming rates of bacteria resistant to last-resort drugs
By Ilene MacDonald

Fears of a "looming" global crisis of antibiotic resistant superbugs intensified this week as new data reveals alarming rates of bacteria resistant to last resort antibiotics that can lead to life-threatening infections across the world.
The problem is due to overuse and misuse of antibiotics, according to researchers, who also rejected the notion that new antibiotics could help resolve the world-wide crisis. (I published an opinion paper stating exactly that 3 or 4 years ago.)

"No matter how many new drugs come out, if we continue to misuse them, they might as well have never been discovered," Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics & Policy (CDDEP) and co-author of the report, "State of the World's Antibiotics, 2015" said in an announcement. Instead, he said the only sustainable solution is to limit overuse and misuse of antibiotics.

One place to start is in the United States, which leads in per capita consumption of antibiotics, according to the report. The nation is also second to China in its consumption of antibiotics in livestock.

And though wealthy countries like the U.S. still use far more antibiotics per capita, the new data reveals high rates of use in low- and middle-income countries. For example, in India, 57 percent of the infections caused by the deadly superbug Klebsiella pneumoniae, were resistant to carbapenem antibiotics, a last-resort drug, in 2014 compared to 29 percent six years earlier. In comparison, these same drugs are still effective against the infections in 90 percent of cases in the U.S. and more than 95 percent of cases in most of Europe.

"Carbapenem antibiotics are for use in the most dire circumstances--when someone's life is in danger and no other drug will cure the infection," said Sumanth Gandra, an infectious diseases physician and CDDEP Resident Scholar in New Delhi, in the announcement. "We're seeing unprecedented resistance to these precious antibiotics globally, and especially in India. If these trends continue, infections that could once be treated in a week or two could become routinely life threatening and endanger millions of lives."

The data also reveals infection rates caused by 12 common and potentially deadly bacteria, including Escherichia coli (E. coli), Salmonella, and methicillin-resistant Staphylococcus aureus (MRSA).

The report outlines six strategies that all countries can follow to halt the spread of resistance:

• Improve water, sanitation and immunization: Better access to clean water and sewerage systems and providing improved coverage for existing and new vaccines will ensure a safe and healthy food supply, reducing the need for antibiotics and thus reducing antibiotic-resistance rates.
Improve hospital infection control and antibiotic stewardship. The report calls for better hygiene, particularly handwashing between patients, and implementation of antibiotic stewardship programs to reduce infection rates. (We have probably reached the point of diminishing return on this one. But, hell, someone feels good saying this. I'll just bet ya this kind of thinking is exactly how some knucklehead came up with Common Core)
• Eliminate economic incentives that encourage antibiotic misuse and overuse in hospitals, communities and agriculture.
• Reduce and eventually phase out antibiotic use for growth promotion in agriculture. (Doh!)
• Educate health professionals, policymakers, and the public on antibiotic use and promote conservation. (More feel good BS!)
• Work with politicians to gain their support for policies to address the threat of antibiotic resistance. (Give me a F'N break will ya?)

Meanwhile, the U.S. has recently taken action to address the growing threat. This week the U.S. Department of Health and Human Services announced the establishment of a Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria to provide advice, information and recommendations to the HHS regarding programs and policies related to combating antibiotic-resistant bacteria. (Typical response, we don't have a f'n clue so let's form a commission to study it some more. Yeah, that's the ticket!)

HHS also announced a strategic alliance with a global biopharmaceutical company to accelerate the development of new drugs to treat multi-drug resistant bacterial infections. (Brilliant, just f'n brilliant! Let's make more antibiotics only do it faster! I really want to meet the chucklehead that came up with that one!) Although the CDDEP report said only 20 percent of efforts should focus on new drug development, (Yeah the other 80% is to do what? Oh, stuff ya know important stuff) HHS said in the announcement that lack of investment in new drugs has helped create a "perfect storm" with the rise of antibiotic-resistant infections. (Now that's some insight rat there, Cap'n Obvious)

The Joint Commission has also launched a Speak Up on Antibiotics campaign to help educate the public on the appropriate and safe use of antibiotics, as well as the risks associated with antibiotic overuse. The campaign includes complete package of free resources, including an infographic, podcast and video. (And I wonder what other "free" stuff might be in that feel good program).
I don't know about yous guys, but I am going to sleep much better tonight Knowing these guys have this under control.
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Old 09-17-2015, 14:10   #2
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Is it true that Cipro is the one and only broad spectrum/general antibiotic magic bullet left in infection control?

Is there much in the antibiotic development pipeline?

The last I remember reading several years ago was that the product development pipeline is anywhere from 7-10 years long and there wasn't much in the way of promise coming thru(antibiotic r&d gap).

I know down here on the civvie side there's been a major shift in recent years to protect antibiotic efficacy. When our kids were born starting 10'years ago, antibiotics were dished out like candy to placate worried parents.

Not anymore thankfully.
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Old 09-17-2015, 14:25   #3
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Is it true that Cipro is the one and only broad spectrum/general antibiotic magic bullet left in infection control? Yes)

Is there much in the antibiotic development pipeline? (No)

The last I remember reading several years ago was that the product development pipeline is anywhere from 7-10 years long and there wasn't much in the way of promise coming thru(antibiotic r&d gap).

I know down here on the civvie side there's been a major shift in recent years to protect antibiotic efficacy. When our kids were born starting 10'years ago, antibiotics were dished out like candy to placate worried parents.

Not anymore thankfully.
The basic problem is the strategic approach we have been taking over the past 75 years. Antibiotic resistance began being noticed within a year or two of the widespread use of penicillin and sulfa drugs.

Think in terms of a UW strategy vs a DA strategy. We have been conducting DA centric actions against insurgent pathogens for 75 years and the insurgents are adapting defenses faster than we can develop weapons (antibiotics).

On the other hand nature has mechanisms to clear the insurgents that just gets overwhelmed at times and the infection leads to disease (note that most infections do not lead to disease otherwise we humans would not survive).

Think UW, i.e. working by, through, and with the indigenous population of cells and force multiplication via an auxillary to enhance the natural defense mechanisms.

We have shown that the UW strategy works very well and it doesn't matter what the insurgent population is.

The hurdle has been educatiing the DA centric folks. I would expect this different strategy to begin appearing in clinical usage in the next 3-4 years.
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Old 09-18-2015, 06:11   #4
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Post-Antibiotic Era

I remember a statement like it was yesterday. I went through the 18D30 course in 1984-85 and the physician that covered ATB Therapy stated, "When Staph A overtakes Vancomycin, we have entered the post-antibiotic era."

That was 30 years ago.....
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Old 09-18-2015, 07:23   #5
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Is it true that Cipro is the one and only broad spectrum/general antibiotic magic bullet left in infection control?
While cipro is still generally effective for its purposes we are seeing an alarming rate of even simple urinary tract infections or kidney infections that are cipro resistant. The rate of E.coli ( the most common UTI bacteria) cipro resistance in my area is as high as 20% which makes it no longer first line for pyelonephritis (kidney infection) in my area.

Just 2 weeks ago I had a young healthy female without a history of UTI or antibiotic treatment present with pyelonephritis with a multidrug resistant E. Coli only sensitive to gentamicin,meropenem, and imipenem.
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Old 09-18-2015, 07:24   #6
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I remember a statement like it was yesterday. I went through the 18D30 course in 1984-85 and the physician that covered ATB Therapy stated, "When Staph A overtakes Vancomycin, we have entered the post-antibiotic era."

That was 30 years ago.....
Exactly, and look how far we have advanced infectious disease therapies.

FYI- See the Opinion I wrote and posted (10/27/13) in the "Drug Resistant Infections" thread in this Forum
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Old 09-18-2015, 08:58   #7
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Trapper,
Thanks for posting,
Will re-post to my kids..

DOL
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Old 09-18-2015, 10:11   #8
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Some discussions I've had with ID docs at WRNMMC (2 yrs ago) seem to lead to a conclusion that in 1st world countries, with the use of 2nd-4th gen ABX being so high, that the 1st gen ABX (PCNs, TCNs, ECNs) are once again becoming effective as the pathogens are mutating to defeat the bigger threats.

Those same ID docs decry the use of the biggest guns early as contributing to the speed of increasing resistance by the pathogens.

I went through the 18D3 course about the same time as SouthernDZ (the second reclass cycle for AD 18 series folks) and we were hit over the head with start small, proper course length, monitor infection life... bigger guns if no change (dependent on affected system/virulence of infection) after a half course...

Why is current protocol that much changed that providers are going directly to Nukes when a 5.56 will work?

Troll sends.
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Old 09-18-2015, 11:04   #9
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Trapper-
Some discussions I've had with ID docs at WRNMMC (2 yrs ago) seem to lead to a conclusion that in 1st world countries, with the use of 2nd-4th gen ABX being so high, that the 1st gen ABX (PCNs, TCNs, ECNs) are once again becoming effective as the pathogens are mutating to defeat the bigger threats.

Those same ID docs decry the use of the biggest guns early as contributing to the speed of increasing resistance by the pathogens.

I went through the 18D3 course about the same time as SouthernDZ (the second reclass cycle for AD 18 series folks) and we were hit over the head with start small, proper course length, monitor infection life... bigger guns if no change (dependent on affected system/virulence of infection) after a half course...

Why is current protocol that much changed that providers are going directly to Nukes when a 5.56 will work?

Troll sends.
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Why is current protocol that much changed that providers are going directly to Nukes when a 5.56 will work?
Not sure why that is??? It makes no good sense to me to apply the strongest drug first. The principles we were taught apply!

Interestingly, a friend is developing a nanoparticle technology to repurpose the older antibiotics. This strategy enables faster uptake and better bioavailability at much lower doses. The data show a much better therapeutic index (lower toxicity threshold) too. This has some real potential IMO. Predictably this strategy should result in less resistance too.

It will be interesting to see the clinical data from this strategy.

I would love to see a broad spectrum like chloramphenicol come back and with a lower toxicity index that could happen. I will keep you posted on the progress.

My approach is, as I said, UW and enhancing the indigenous innate immune response. That way those insurgents are never challenged by the drug in the first place.
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Old 09-18-2015, 11:16   #10
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One afterthought to your question xSF Med - the answer to your question may lie in economics and not medicine. Current healthcare economics demand less hospital time. The thinking, therefor, may be "I will give this ID patient the big gun and get him/her out sooner thus reducing the hospital time and therefore the cost."

Short term thinking. Second and third order effects are the patient needs to be re-admitted and now may have a drug resistant infection. Payers refusal to pay for re-admissions may turn that logic around though.

I can see a similar rationale playing out in outpatient clinics as well.

Just a thought.
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Old 09-18-2015, 11:57   #11
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One afterthought to your question xSF Med - the answer to your question may lie in economics and not medicine. Current healthcare economics demand less hospital time. The thinking, therefor, may be "I will give this ID patient the big gun and get him/her out sooner thus reducing the hospital time and therefore the cost."

Short term thinking. Second and third order effects are the patient needs to be re-admitted and now may have a drug resistant infection. Payers refusal to pay for re-admissions may turn that logic around though.

I can see a similar rationale playing out in outpatient clinics as well.

Just a thought.
Are the docs not thinking of long term toxicity and organ damage with some of these ABX tx's? A short term stay now and more expensive long term care in the future? some of the newer big gun broad spectrum ABX therapies have systemic effects that are delayed by months and years - neuro-muscular, renal, hepatic, hemo, cardiac and pure neuro... and these effects are exascerbated by the compromised immune system and the pathogen itself. I guess I'm old school and still think in the terms of Primum Non Nocere, across the board... harm comes immediately, economically and in quality of life terms, IMOO. YMMV.
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Old 09-18-2015, 12:24   #12
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Are the docs not thinking of long term toxicity and organ damage with some of these ABX tx's? A short term stay now and more expensive long term care in the future? some of the newer big gun broad spectrum ABX therapies have systemic effects that are delayed by months and years - neuro-muscular, renal, hepatic, hemo, cardiac and pure neuro... and these effects are exascerbated by the compromised immune system and the pathogen itself. I guess I'm old school and still think in the terms of Primum Non Nocere, across the board... harm comes immediately, economically and in quality of life terms, IMOO. YMMV.
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Are the docs not thinking of long term toxicity and organ damage with some of these ABX tx's?
My gut reaction was YGTBSM! Who or what group is taking a long-term view of anything anymore??? Name one!

I can tell from the passion in your post that this shit drives you batshit f'n crazy too! That is why I posted the reply to VG's lament about Intel in another thread (cross-thread points please). Exactly the same thing is present in the medical field.

It seems to me that the solutions to problems we face (pick one...any one) are obvious if people would just take their collective heads out of their 4th point of contact.

[Sigh]
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Old 09-18-2015, 12:26   #13
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All good thoughts gentlemen.

As far as the "big guns" I agree with appropriate antibiotic stewardship and reserving the big guns for sepsis. In this case it does not pay to start narrow. Remember that if the patient has sepsis then broad spectrum antibiotics are appropriate and studies suggest that a patient's mortality increases ~7% per hour that they are not appropriately covered.

I would like to throw out C.diff into the equation as well. I bring it up in every one of my talks with patients regarding antibiotic treatment vs conservative treatment. C.diff colitis ranges from bad diarrhea, to severe dehydration and renal failure, to sepsis and even megacolon with colectomy. It is not that rare and we see that whole spectrum regularly. There's even "community acquired" C. diff and I've seen people without recent antibiotic treatment get it.

The discussion about C.diff helps more than the resistance talks because it is a more tangible consequence. I can not tell you how much time is spent explaining to people that antibiotics are not needed for their "cold" they have had for 2 days or 3 hours because their primary doctor or pediatrician has "always done that". I tell them that they should see them then. It doesn't sit well but we have to fight the good fight or become part of the problem.
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Old 09-18-2015, 12:49   #14
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I've been following this thread closely and have not yet shared my $.02.

Regarding comments about late toxicities (months to years out from Rx) of antibiotics - I'd like to hear which specific antibiotics to which you are referring, xSFmed, along with the reported late toxicities to further have discussion on this - peer-reviewed medical literature references would be appreciated.

Antibiotic stewardship is a very complex and dynamic area of medicine. In my field of expertise we treat profoundly immunocompromised patients who have no immunologic reserve and can go from well-appearing to dead in a matter of hours, so our treatment algorithms typically start broad and go to narrow - the opposite of what should be done for otherwise immunocompetent patients.

When I did primary care, I was slow to start antibiotics for infections, knowing many would be contained and cleared by the body, after that, I did start narrow and assess response when in an outpatient setting.

In the inpatient setting, things get much stickier, particularly due to insurance company models of reimbursement (bundled payment for hospitalization regardless of duration based upon diagnoses). Doctors have to weigh cost of treatment and, more importantly, duration of hospitalization with potentials for toxicities and emergence of drug-resistant bacteria. The major contributors to drug-resistant bacteria are truncated antibiotic courses (typically due to non-compliance of patients in the outpatient setting), and demand for antibiotics by the consumer for non-serious and non-bacterial infections. If physicians start narrow and slowly broaden in the inpatient setting, hospitals will take huge losses for each prolonged hospitalization due to starting narrow which, ultimately, will lead to bankruptcy and closure of the hospitals which physicians see as more harmful to patients and the general population than starting a "big gun" antibiotic from the start.

In the end, I believe the two major issues are patient demands for antibiotics when they aren't warranted, and patients stopping antibiotics courses early when they feel better, as opposed to completed a prescribed course to ensure clearance of the infection. These, IMHO, far outweigh the preferential use of "big gun" antibiotics up front for infections requiring hospitalization for management.

YMMV...
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Old 09-18-2015, 12:50   #15
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All good thoughts gentlemen.

As far as the "big guns" I agree with appropriate antibiotic stewardship and reserving the big guns for sepsis. In this case it does not pay to start narrow. Remember that if the patient has sepsis then broad spectrum antibiotics are appropriate and studies suggest that a patient's mortality increases ~7% per hour that they are not appropriately covered.

I would like to throw out C.diff into the equation as well. I bring it up in every one of my talks with patients regarding antibiotic treatment vs conservative treatment. C.diff colitis ranges from bad diarrhea, to severe dehydration and renal failure, to sepsis and even megacolon with colectomy. It is not that rare and we see that whole spectrum regularly. There's even "community acquired" C. diff and I've seen people without recent antibiotic treatment get it.

The discussion about C.diff helps more than the resistance talks because it is a more tangible consequence. I can not tell you how much time is spent explaining to people that antibiotics are not needed for their "cold" they have had for 2 days or 3 hours because their primary doctor or pediatrician has "always done that". I tell them that they should see them then. It doesn't sit well but we have to fight the good fight or become part of the problem.
Great points Doc!

I really like the C. Diff example. With your permission, I am going to borrow that thought to use it when I am talking to the Chruckleheads.
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