Post-Antibiotic Era—the Antibiotic Apocalypse--is Upon Us?

With terror in the headlines last week, a potentially more deadly development got short play. Bacteria have become resistant to the last universally effective antibiotic (colistin), and the mutation is spreading quickly (20% of pigs tested in China, 16 patients, now in Laos and Malaysia, a range of bacterial strains and species, including E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.)

“Bacteria becoming completely resistant to treatment - also known as the antibiotic apocalypse - could plunge medicine back into the dark ages.” That means that some day in the not-too-distant future, medicine may have little to support your fight against common infections, and routine surgery will become a very risky enterprise, indeed.

Antibiotic resistance: World on cusp of 'post-antibiotic era'
http://www.bbc.com/news/health-34857015

***********************************************************

I was briefly heartened to read that WHO is on the job—until I visited their website on Antibiotic Resistance Week (Nov 16-22). Now I wonder if agency so roundly criticized for response to Ebola, is capable of organizing a global campaign to develop new antibiotics, and to cease the practices that leads to development and spread of resistance to these new antibiotics in hospital, animal husbandry, and outpatient care. Hopefully they are finding success in energizing decision-makers(?)

WHO Antibiotic Awareness Week (Nov 16-22, 2015)
http://www.who.int/mediacentre/events/2015/world-antibiotic-awareness-week/event...

**********************************************************

FYI, buried in the WHO website, was
Ten Facts on Antimicrobial Resistance
http://www.who.int/features/factfiles/antimicrobial_resistance/facts/en/index9.h...

1. What is antimicrobial resistance?
Antimicrobial resistance is the ability of a microorganism (like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics, antivirals and antimalarials) from working against it. As a result, standard treatments become ineffective, infections persist and may spread to others.

2. Drug resistance is a global problem
Over the past years, the use and misuse of antimicrobials has increased the number and types of resistant organisms. Consequently many infectious diseases may one day become uncontrollable. With the growth of global trade and travel, resistant microorganisms can spread promptly to any part of the world.

3. What causes drug resistance?
Drug resistance is a natural evolutionary phenomenon. When microorganisms are exposed to an antimicrobial, the more susceptible organisms succumb, leaving behind those resistant to the antimicrobial. They can then pass on their resistance to their offspring.

4. Inappropriate use of medicines worsens drug resistance
Inappropriate use of antimicrobials drives the development of drug resistance. Both overuse, underuse and misuse of medicines contribute to the problem. Ensuring that patients are informed about the need to take the right dosage of the right antimicrobial requires action from prescribers, pharmacists and dispensers, pharmaceutical industry, the public and patients, as well as the policy makers.

5. Lack of quality medicines contributes to drug resistance
Most drug quality assurance systems are weak. This can lead to poor quality medicines, exposing patients to sub-optimal concentrations of antimicrobials, thus creating the conditions for drug resistance to develop. In some countries poor access to antimicrobials forces patients to take incomplete courses of treatment or to seek alternatives that could include substandard medicines.

6. Animal husbandry is a source of resistance to antibiotics
Sub-therapeutic doses of antibiotics are used in animal-rearing for promoting growth or preventing diseases. This can result in resistant microorganisms, which can spread to humans.

7. Poor infection prevention and control amplifies drug resistance
Poor infection prevention and control can increase the spread of drug-resistant infections. Hospitalized patients are one of the main reservoirs of resistant microorganisms. Patients who are carriers of resistant microorganisms can act as a source of infection for others.

8. Weak surveillance systems contribute to the spread of drug resistance
While surveillance for the emergence of drug resistant TB and HIV infection is improving, currently there are few well-established networks that regularly collect and report relevant data on drug resistance. Some countries lack laboratory facilities that can accurately identify resistant microorganisms. This impairs the ability to detect emergence of resistance and take prompt actions.

9. The pipeline for new tools to combat drug resistance is almost dry
Existing antibiotics and anti-parasitic drugs, and, to a lesser extent, antiviral drugs, are losing their effect. At the same time there is insufficient investment in developing new antimicrobials. Similarly, there is insufficient new research into new diagnostics to detect resistant microorganisms; and new vaccines for preventing and controlling infections. If this trend continues, the arsenal of tools to combat resistant microorganism will soon be depleted.

10. WHO calls on stakeholders to combat drug resistance
The threat from drug resistance is increasing. There is a need for urgent action; everyone must play a part. The complex problem of drug resistance requires collective action. WHO has developed a draft global action plan to combat antimicrobial resistance which has been submitted to the sixty-eighth World Health Assembly, taking place in May 2015. Governments will be asked to approve the plan and, in doing so, declare their commitment to address this global health threat.

Is there any hope with more effort in synthetic anti-bacterials?

Sure hope researchers have something to offer, and soon! And that governments find a better way to produce than the system that brings us heavily merchandised lifestyle drugs. And that all misuse is strictly curtailed, so we don't quickly lose any new antibiotic's usefulness.

In The Coming Plague, Laurie Garrett ends by suggesting that large, congested populations (like Mexico City) would be place where some new plague could take off. South Asia and the Middle East seem full of such populations, including refugee camps, where it seems the latest antibiotic resistance could easily spread(?)

My great great grandfather, a carpenter, died of gangrene from a splinter in the 19th c. A few years ago, his g'g'nephew (my uncle) died of hospital-acquired MRSA*--in spite of all the latest antibiotics, vacuum equipment and subsequent surgeries to physically address the infection. My uncle, unlikely survivor of WW2 and many heart attacks, marveled that a bug would be what killed him.

*Methicillin-resistant Staphylococcus aureus

There is this, though: https://www.bostonglobe.com/news/science/2015/01/07/northeastern-researchers-dis...

Yay--keep 'em coming! :-)

We can help by using meds as prescribed and seeking out meat raised without antibiotics. Some restaurants like Panera and Chipotle are sourcing meats raised without antibiotics--or at least only as needed, and not for growth: http://time.com/4033496/fast-food-antibiotics/

We rely on evolutionary processes to find antibodies. Only our use of antibacterial treatment is likely speeding bacterial defensive evolution faster than defenses against bacteria develop.

We may need more success with synthetic antibacterial medicines. Perhaps there can be steady development to stay ahead of bacterial evolution.

I also wish the craze for adding antimicrobials to soaps and lotions goes away. Totally bad idea.

>7 Marissa_Doyle: Yes!

How many of you challenge your immune systems by going ahead and consuming foods that might have higher bacterial counts than recommended?

"Superbugs Are Everywhere"

http://www.slate.com/articles/health_and_science/medical_examiner/2015/11/antibi...

>8 2wonderY: Not so much that, but I did encourage my kids play in the dirt and get thoroughly grubby when they were little, to give their immune systems some exercise.

2,6 synthetic antibacterials

My understanding is that pharmaceutical companies will tweak an existing med to keep it from generic makers a bit longer, so possible they might try tweaking an antibiotic enough to evade bacterial defenses, while keeping its potency? I doubt they would attempt to synthesize an entirely new class of antibiotic, though. More likely to find new antibiotics in nature?

Like vaccines, there is less profit in antibiotics than those for chronic or lifestyle conditions, because brief, one-time course of treatment (unless adding to animal feed).

Bacteriocins sound like potentially good news for those of us in first world! Not so much for the rest of humanity, though? Big Pharma would no doubt be happy to produce targeted antibiotics--and charge $$$$ to desperate patients, no? We would need a different system for production if bacteriocins pan out and if they are to be made as available for appropriate use as traditional antibiotics?

Believe me, I would be extremely happy, if the Post-Antibiotic Era / Antibiotic Apocalypse was cancelled by technology--accessible and affordable preferred.

I mentioned this discussion to a biologist buddy of mine.

He sent me this article.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159373/#__sec20title

It wouldn't be the 'Dark Ages'; my mother lived in times pre-antibiotics. It just would be very bad.

>14 richardbsmith: Very good article. Thanks for sharing it.

> 14 Nice overview, thanks.

Search for new antibiotics won't be cheap or without bumps, e.g., kill antibiotics without undue harm to our mitochondria & their ribosomes, our microbiome, other side effects...

(Scary when I think back to stuff my international kids were exposed to--several anti-parasite meds (poisons, actually) for sever diarrhea, a year of anti-TB antibiotics for son apparently strongly exposed, a new antibiotic (for series of ear infections) that later proved problematic. Potentially health-saving and worth while, but real eye-opener if these were the SAFE efficacious antibiotic agents. Also amazing is the extent of health problems one can face elsewhere in the world--and my kids spent first few years in care of relatively good hospitals and institutions, and were considered healthy in comparison to many!)

It seems to be the case that a lot of scientific/technological advance follows this pattern: a new technology is discovered -- lead for water pipes, coal-burning steam engines, X-rays, nuclear power, -- which lead to increased human welfare. Then ... the unpredicted negative consequences appear. But then ... we make further progress and get the negative consequences under control, if not completely suppressed.

One hopes that this will be repeated with anti-biotics, and/or that in this century we make such leaps in understanding biology that altogether new approaches to enhancing our physical welfare emerge.

We're Eating Less Meat—But Using More Antibiotics on Farms Than Ever

The meat industry's massive appetite for antibiotics just keeps growing. That's the takeaway from the Food and Drug Administration's latest annual assessment of the issue, which found that agricultural use of "medically important" antibiotics—the ones that are prescribed to people when they fall ill—grew a startling 23 percent between 2009 and 2014. Over the same period, the total number of cows and pigs raised on US farms actually fell a bit, and the number of chickens held steady. What that's telling us is that US meat production got dramatically more antibiotic-dependent over that period.

Even more disheartening, medically important antibiotic use crept up 3 percent in 2014 compared to the previous year—despite the FDA's effort to convince the industry to voluntarily ramp down reliance on such crucial medicines. True, the FDA's policy, which was first released in 2012, contained a "three-year time frame for voluntary phase-in." One might have hoped, however, that by 2014, the needle would point downward, not implacably upward...

http://www.motherjones.com/tom-philpott/2015/12/meat-industry-still-cant-get-eno...

I'm hoping organic chicken is less problematic, but I read that 2-3% of wildlife near hospitals and industrial farms have some resistant strains of bacteria. (What were farmers doing with colistin, the drug of last resort?? Will they latch on and ruin new discoveries?)

A friend of mine owned a chicken farm that supplied a very well known U.S. chicken retailer. It was really big warehouses where chickens were kept from hatchlings until "harvest." They were fed a blend of protein, antibiotics, and steroids for the very few weeks it took them to become broilers. Three days before "harvest" the feed was switched to a "natural" diet...please pay no attention to what was already thick on the floor. Then these freaks of nature were taken away for slaughter.

Americans have been eating this for years. Six weeks for an egg to a chicken to slaughter. Has anyone paid attention to the changes in the average age of puberty....or the incidence of obesity? Every action has a reaction.

I recall the 25 cent a pound chicken where I last lived in the US, which I spent a great deal of time cutting the fat from. Here is Slovenia I remove the skin usually, but there is very little fat. They are also much smaller beasts. Something is very wrong with US chicken.

I raised chickens of my own for a time. There are different kinds of chicken. The first breed of bird I raised were small, lean birds with not much fat. More like pheasants. The meat was very rich. The second group I raised were very large, almost got too big, their legs went wonky and when plucked they were the size of a small turkey....they had more fat on them as well. The biggest difference I have noticed between home grown and store chickens is the taste. And of course all the goodies stuffed into the by big business meat producers to boost profits.

Since Lancet report, ultimate superbug gene has been discovered in at least a dozen countries including Canada: a human patient in Ottawa, two ground beef samples in Ontario.

http://www.thestar.com/news/world/2016/01/05/disturbing-drug-resistant-superbug-...

High-profile, British-funded report (Dec. 2014):

"...A project commissioned by the British government has released estimates of the near-future global toll of antibiotic resistance that are jaw-dropping in their seriousness and scale: 10 millions deaths per year" (globally by 2050) ", more than cancer, and at least $100 trillion in sacrificed gross national product..."

http://www.wired.com/2014/12/oneill-rpt-amr/
http://amr-review.org/

***************************************************

Pharmaceutical companies (Jan. 2016):

"...Governments must help solve the problem of no new antibiotics by funding and creating incentives for developing new drugs, almost 100 pharmaceutical companies and trade associations say in a statement being released this evening at the World Economic Forum in Davos...."

http://phenomena.nationalgeographic.com/2016/01/20/davos-declaration/
http://amr-review.org/industry-declaration

Researchers at the University of British Columbia have discovered a rare clay used as medicine by aboriginals in northern B.C. contains antibacterial properties that could be used to treat antibiotic-resistant bacteria.

http://www.vancouversun.com/health/rare+clay+used+aboriginals+found+kill+bacteri...

The United States' first known case of a superbug that cannot be killed by any existing antibiotic was announced Thursday...

http://www.cnn.com/2016/05/26/health/first-superbug-cre-case-in-us/

And at the UN, they are ... talking. Leaders solidified their commitment to develop action plans for their countries. The public was called upon to not demand antibiotics for ailments like colds, for which they are unnecessary. Oh, and "groups like the WHO and the Food and Agriculture Organization of the United Nations (FAO) were called upon to collaborate on the issue with multiple stakeholders and report back on efforts at the UN General Assembly in 2018". http://time.com/4502752/superbugs-are-a-major-global-threat/

ETA: Well, great, after all that talk, UN declares we must do something, but no 2-year targets. The threat of a global economic downturn (via agriculture) worse than 2008's seems to be driving this "action" more than human health! http://www.npr.org/sections/goatsandsoda/2016/09/21/494914739/u-n-pledges-to-fig...

Meanwhile, antibiotic-resistant gonorrhea made its first appearance in the US (Hawaii).

Just happened onto this thread. I have heard a couple of Science Friday shows on this topic. I was able to find one at: http://www.sciencefriday.com/segments/old-ideas-may-help-us-fight-new-superbugs/

I know bacteriophages are mentioned at one point as an alternative to antibiotics.

Anyone else have tv commercials in their area ridiculing concerns over antibiotics in chickens? A big effort here in North Carolina- chicken feet producer for China ;-)

edit: I guess it would be better phrased " antibiotics used in producing chickens for consumption ". As I understand it the mass introduction of antibiotics into the environment results in resistance development by various & sundry bacteria.

Thanks. Yeah, I'm sure in time we will come up with alternatives, though after much expenditure and loss of life (my uncle, for one). The NYT article with its mention of economic impact makes me think that any new remedies will be shared with agricultural business, perhaps to be lost again? (Pharmaceutical companies will want return on their investment so either new products either very expensive or serving as big a market as possible--including pigs if utility as growth enhancer?)

Rare Superbug Gene Discovered on U.S. Pig Farm

Researchers have found a rare and frightening superbug gene on a U.S. pig farm and say their discovery suggests raw meat could carry the dangerous germs into the human population....

No pigs scheduled for slaughter carried the mutant gene, the researchers stressed, and they haven't found any threat to people yet.

The gene is called bla IMP-27 and it gives bacteria the ability to resist the effects of a class of antibiotics called carbapenems.

Carbapenems are considered an antibiotic of last resort, so germs that resist their effects are very difficult to kill.

Worse, this superbug gene is carried on an easily swapped bit of genetic material called a plasmid, and the researchers found it in several different species of bacteria on the farm.

That suggests the bacteria have been passing the gene around...

http://www.nbcnews.com/health/health-news/researchers-find-rare-superbug-gene-us...

Capitalism is not conducive to health in many ways, not the least of which is in regard to food production.

As FDA seems unable to manage antibiotic use by meat-producers, we should endeavor to eat less meat, eat organic, eat wild? (Although antibiotic-resistant bacteria is being detected in wild animals near farms and hospitals...at low levels, but still! )

December 22, 2016

The U.S. Food and Drug Administration today published its annual report summarizing sales and distribution data for all antimicrobial drugs approved for use in food-producing animals. The report shows that sales and distribution of all antimicrobials increased 1 percent from 2014 through 2015, tying for the lowest annual increase since 2009. The percentage of those antimicrobials that are considered medically important in human medicine increased by 2 percent from 2014 through 2015...

http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm534244.htm

(Nevada)
A Woman Was Killed by a Superbug Resistant to All 26 American Antibiotics:
She won’t be the last.
https://www.theatlantic.com/health/archive/2017/01/a-superbug-resistant-to-26-an...

Resistance to the Antibiotic of Last Resort Is Silently Spreading:
Just over a year after they were discovered in China, bacteria that can fend off colistin are being found all across the world.
https://www.theatlantic.com/health/archive/2017/01/colistin-resistance-spread/51...

I heard a Dr. on a recent The People's Pharmacy radio show mention the amount of antibiotics put into the water at factories - especially in places like India and China. The Dr. from California I believe, mentioned the water in the river below a drug manufacturer has enough Ciprofloxacin, the antibiotic, in it to treat everyone in Switzerland for a year.

Here is an article I found about a place in India that may the one cited above:

http://usatoday30.usatoday.com/tech/science/environment/2009-01-26-drug-india-st...

WHO: These 12 bacteria pose greatest risk to human health

..."The top three (bacteria) have nothing to treat them," said Dr. Vicky Enne, a clinical microbiologist at UCL in the UK....

The second and third groups name bacteria that are increasingly showing resistance against the main drugs used against them, but which still have a few options remaining. "These still have some drugs to fight them ... but doctors are being forced to use last resort drugs because resistance levels are so high," Enne said...

http://www.cnn.com/2017/02/27/health/who-bacteria-antibiotics-list-amr/

>37 margd: I heard on Science Friday I believe, that "discovery" of potential antibiotics is where the bottle neck is. Said that "development" after discovery is pretty good. Also mentioned was how few bacteria are easy to grow in culture. A quote from the institute of health:" Environmental microbiologists estimate that less than 2% of bacteria can be cultured in the laboratory."

Deadly fungal infection that doctors have been fearing now reported in U.S.

Nearly three dozen people in the United States have been diagnosed with a deadly and highly drug-resistant fungal infection since federal health officials first warned U.S. clinicians last June to be on the lookout for the emerging pathogen that has been spreading around the world.

The fungus, a strain of a kind of yeast known as Candida auris, has been reported in a dozen countries on five continents starting in 2009, where it was first found in an ear infection in a patient in Japan. Since then, the fungus has been reported in Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Korea, Venezuela and the United Kingdom.

Unlike garden variety yeast infections, this one causes serious bloodstream infections, spreads easily from person to person in health-care settings, and survives for months on skin and for weeks on bed rails, chairs and other hospital equipment. Some strains are resistant to all three major classes of antifungal drugs. Based on information from a limited number of patients, up to 60 percent of people with these infection have died. Many of them also had other serious underlying illnesses.

...Among infectious disease clinicians and laboratory personnel, infections involving fungi don't typically ring the same kind of alarm bells as antibiotic-resistant bacteria - until now...

http://www.sacbee.com/news/nation-world/national/article137943703.html#storylink...

'Nightmare bacteria' are trying to spread in the U.S., CDC says
Aggressive testing at hospitals and clinics can stop superbugs
Maggie Fox / Apr.03.2018

...The CDC tried out a new system aimed at quickly identifying these superbugs. They’ve helped staff up state health departments and labs to speedily test samples so that hospitals, clinics and other facilities can rapidly isolate patients infected with them.

...The results were sobering. One in four of the samples sent in carried superbug genes, the CDC team reported. When the facilities involved looked further, they found 11 percent of seemingly unaffected people screened carried such germs without having any symptoms.

...Healthy people can unknowingly transmit the germs to a cancer patient, someone getting an organ transplant, a vulnerable newborn or a frail elderly person. That’s when an infection can take hold and kill.

“What the CDC is highlighting is the need, once you identify people carrying these bugs, to screen them and also their contacts to make sure they haven’t passed these bugs,” Price said....

https://www.nbcnews.com/health/health-news/nightmare-bacteria-are-trying-spread-...

______________________________________________________

Kate Russell Woodworth et al. 2018. Vital Signs: Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms — United States, 2006–2017
CDC. https://www.cdc.gov/mmwr/volumes/67/wr/mm6713e1.htm?s_cid=mm6713e1_w

...Abstract...Conclusions: The proportion of Enterobacteriaceae infections that were (carbapenem-resistant Enterobacteriaceae CRE) remained lower and decreased more over time than the proportion that were ESBL phenotype (pathogens that were nonsusceptible to extended-spectrum cephalosporins). This difference might be explained by the more directed control efforts implemented to slow transmission of CRE than those applied for ESBL-producing strains. Increased detection and aggressive early response to emerging antibiotic resistance threats have the potential to slow further spread...

This material uses energy from ambient light to kill hospital superbugs
Maria Temming | April 10, 2018

...Ethel Koranteng, a chemist at University College London...and colleagues developed a material to make hospital surfaces self-disinfecting. Naturally antimicrobial metals such as copper and steel are difficult to sculpt around uneven surfaces. But the new polymer-based material could be fashioned into a flexible film that covers computer keyboards, or molded into rigid, plasticlike casings that enclose phone handles, bedrails and other surfaces especially prone to contamination.

...activated by overhead lighting,

The covering is made of polyurethane embedded with tiny semiconductor nanoparticles called quantum dots and particles of a purple dye called crystal violet. When the quantum dots absorb ambient light, they transfer some of that energy to nearby dye particles, causing the crystal violet to release a kind of high-energy oxygen molecule that kills microbes.

In lab tests, the material killed 99.97 percent of MRSA, the strain of Staphylococcus aureus that is resistant to methicillin and other antibiotics, and 99.85 percent of a multidrug-resistant strain of E. coli...

Citations

E. Koranteng et al. Light-activated surfaces for reducing hospital acquired infections. Materials Research Society meeting, Phoenix, April 5, 2018...

https://www.sciencenews.org/article/material-uses-energy-ambient-light-kill-hosp...

>41 margd: Holy crap! How does someone have the expertise and imagination to even conceive of something like that? I hope it implementable.

>41 margd: Call me paranoid but I worry about the 0.03 percent of MRSA that isn't killed. Aside from that, I think the science behind this is amazing.

On a totally unrelated note, what an awesome name for a rock band, Crystal Violet.

>41 margd: Could the "kind of high-energy oxygen molecule" be ozone? Could there be unintended side-effects of releasing all this ozone around patients?

>44 jjwilson61: ozone?

ROS--Reactive Oxygen Species, I think, which sounds like it could be ozone. (Presentation rather than paper, so no detailed methods.) When you're talking nanoparticles 2-10 nm in diameter, though, I suspect amounts are minute and localized?

It took a summer ~ten years ago for MRSA to kill my uncle, so I had lots of opportunities to observe and wonder about his hospital's efforts to quarantine the bug. We had to don fresh gowns, etc. in his hospital room, but not in ICU. I was surprised that entrance/exit to ICU was controlled by those palm door-openers, rather than motion detectors. (Alcohol disinfectant was adjacent, though.) Be great if this new material works for palm door-openers, elevator buttons, light switches, etc. (And for keyboards...mine is acting up...)

Antibiotics in Meat Could Be Damaging Our Guts
William D. Cohan | May 25, 2018

The F.D.A. banned the use of antibiotics for growth promotion in animals last year. One organic cattle farmer is sure the ban is being flouted.

...of all the “medically important” antibiotics sold in the United States — that is, those used to treat human disease — about 70 percent (still) goes into the feed and water of animals

...Beyond the threat of drug-resistant illness, there is evidence of another risk from antibiotic overuse in pigs, poultry and cattle: the possibility that people who consume antibiotic-laced meat will get some of the drugs, as well as resistant bacteria, into their own digestive tracts — with potentially harmful results.

A growing body of scientific research also shows that the antibiotics we take as medicine can disrupt our so-called gut microbiome, the bacteria that live happily in our stomach and intestines and that are the key to our ability to properly digest food and process fats. This disruption has been linked to the rise of noncommunicable diseases such as obesity, juvenile diabetes, asthma and allergies. Some researchers also believe that alterations in the gut microbiome have led to an increase in the incidence of autism, Alzheimer’s and Parkinson’s disease.

...(Avinash Kar, a senior attorney at the Natural Resources Defense Council) notes that Denmark uses about 30 percent less antibiotics a year on a per-kilogram of meat basis than American farms do. But he applauds the fact that big chicken producers like Perdue, Tyson and Foster Farms have reduced or eliminated antibiotic use in the feed, perhaps under pressure from their biggest customers, including KFC, McDonald’s and Subway, which now claim in their advertising that all or some of the chicken they serve has been raised without antibiotics. He thinks beef and pork producers should follow suit...

ps://www.nytimes.com/2018/05/25/opinion/sunday/meat-antibiotics-organic-farming.html

I think from now on I'll wear Crocs (plastic footwear) when I visit hospital--and throw them in washer (with chlorine bleach) as soon as I get home!

Culture of Secrecy Shields Hospitals With Outbreaks of Drug-Resistant Infections
The lack of transparency puts patients at risk, some say. Institutions say disclosure could scare some people away from seeking needed medical care.

Andrew Jacobs and Matt Richtel | April 8, 2019

In January, the Centers for Disease Control and Prevention sent out an urgent public alert about a deadly bacteria, resistant to virtually every known antibiotic, that sickened more than a dozen Americans who had elective surgery at Grand View Hospital in Tijuana, Mexico.

But when similar outbreaks take place at hospitals on American soil, the C.D.C. makes no such public announcement. That is because under its agreement with states, the C.D.C. is barred from publicly identifying hospitals that are battling to contain the spread of dangerous pathogens...

https://www.nytimes.com/2019/04/08/health/candida-auris-hospitals-drug-resistant...

-------------------------------------------------------------------------------------------------------------------

A Mysterious Infection, Spanning the Globe in a Climate of Secrecy
The rise of Candida auris embodies a serious and growing public health threat: drug-resistant germs. (9:02) Revenge of the Bacteria: Why We’re Losing the War
Bacteria are rebelling. They’re turning the tide against antibiotics by outsmarting our wonder drugs. This video explores the surprising reasons.CreditCreditMelissa Golden for The New York Times

Matt Richtel and Andrew Jacobs | April 6, 2019

...a fungus called Candida auris, preys on people with weakened immune systems, and it is quietly spreading across the globe. Over the last five years, it has hit a neonatal unit in Venezuela, swept through a hospital in Spain, forced a prestigious British medical center to shut down its intensive care unit, and taken root in India, Pakistan and South Africa.

Recently C. auris reached New York, New Jersey and Illinois, leading the federal Centers for Disease Control and Prevention to add it to a list of germs deemed “urgent threats.”

...Nearly half of patients who contract C. auris die within 90 days, according to the C.D.C. Yet the world’s experts have not nailed down where it came from in the first place.

“It is a creature from the black lagoon,” said Dr. Tom Chiller, who heads the fungal branch at the C.D.C., which is spearheading a global detective effort to find treatments and stop the spread. “It bubbled up and now it is everywhere.”

...genome sequencing showed that there were four distinctive versions of the fungus, with differences so profound that they suggested that these strains had diverged thousands of years ago and emerged as resistant pathogens from harmless environmental strains in four different places at the same time.

...Dr. Meis, the Dutch researcher, said he believed that drug-resistant fungi were developing thanks to heavy use of fungicides on crops.

Dr. Meis became intrigued by resistant fungi when he heard about the case of a 63-year-old patient in the Netherlands who died in 2005 from a fungus called Aspergillus. It proved resistant to a front-line antifungal treatment called itraconazole. That drug is a virtual copy of the azole pesticides that are used to dust crops the world over and account for more than one-third of all fungicide sales.

A 2013 paper in Plos Pathogens said that it appeared to be no coincidence that drug-resistant Aspergillus was showing up in the environment where the azole fungicides were used. The fungus appeared in 12 percent of Dutch soil samples, for example, but also in “flower beds, compost, leaves, plant seeds, soil samples of tea gardens, paddy fields, hospital surroundings, and aerial samples of hospitals.”

Dr. Meis visited the C.D.C. last summer to share research and theorize that the same thing is happening with C. auris, which is also found in the soil: Azoles have created an environment so hostile that the fungi are evolving, with resistant strains surviving.

This is similar to concerns that resistant bacteria are growing because of excessive use of antibiotics in livestock for health and growth promotion. As with antibiotics in farm animals, azoles are used widely on crops.

“On everything — potatoes, beans, wheat, anything you can think of, tomatoes, onions,” said Dr. Rhodes, the infectious disease specialist who worked on the London outbreak. “We are driving this with the use of antifungicides on crops.”..

https://www.nytimes.com/2019/04/06/health/drug-resistant-candida-auris.html?modu...

Potentially good news. Bet it will be prohibitively expensive, though not compared to the two months in hospital, two surgeries and other treatments my uncle endured before MRSA finally killed him...

Scientists Modify Viruses With CRISPR To Create New Weapon Against Superbugs
Rob Stein | May 22, 2019 (Heard on Morning Edition)

...a new kind of antibiotic made out of viruses that have been genetically modified using the gene-editing tool CRISPR.

"What CRISPR is able to do is something that we've not been able to do before. And that is, very selectively modify genes in the viruses to target the bacteria," Priebe says.

Later this year, Dr. Michael Priebe and his colleagues plan to start infusing cocktails containing billions of bacteriophages genetically modified with CRISPR into patients at six centers around the United States.

"If we're successful, this revolutionizes the treatment of infections," he adds. "This can be the game changer that takes us out of this arms race with the resistant bacteria and allows us to use a totally different mechanism to fight the pathogenic bacteria that are infecting us."

The approach, developed by Locus Biosciences of Morrisville, N.C., involves viruses known as bacteriophages (called phages for short). Phages are the natural enemies of bacteria. They can infect and destroy bacteria by reproducing in large numbers inside them until the microbes literally explode.

Locus scientists have created a cocktail of three phages that have been modified using CRISPR, which was discovered by studying the immune systems of bacteria.

"What we've learned how to do is reprogram that immune system to attack itself," says Paul Garofolo, the company's CEO. "We load the viruses up with CRISPR constructs, which essentially work like little Pac-Men. They go into a target bacteria cell, and they chew up the DNA of that target. It makes them much more potent killers."

Locus is one of several companies that are trying to use CRISPR to fight health problems by targeting only bad bacteria in the body and leaving the good ones alone...

https://www.npr.org/sections/health-shots/2019/05/22/723582726/scientists-modify...

Article mentions inappropriate dumping of untreated wastewater and sewage in lower income countries, but old, combined storm and sewers in North America release untreated sewage during storm events, which are becoming more common with climate change. Dittos spills from animal waste on farms...

( In addition to antibiotic resistance, drugs and other endocrine disrupting chemicals released to the atmosphere are blamed for widespread feminization of male vertebrates from fish to alligators--and possible people... https://news.nationalgeographic.com/2016/02/160203-feminized-fish-endocrine-disr... )

World's rivers 'awash with dangerous levels of antibiotics'
Largest global study finds the drugs in two-thirds of test sites in 72 countries

Natasha Gilbert | 26 May 2019

...Antibiotic pollution is one of the key routes by which bacteria are able develop resistance to the life-saving medicines, rendering them ineffective for human use. ...The rise in antibiotic-resistant bacteria is a global health emergency that could kill 10 million people by 2050, the UN said last month.

The drugs find their way into rivers and soil via human and animal waste and leaks from wastewater treatment plants and drug manufacturing facilities. “It’s quite scary and depressing. We could have large parts of the environment that have got antibiotics at levels high enough to affect resistance,” said Alistair Boxall, an environmental scientist at the University of York, who co-led the study... presented on Monday at a conference in Helsinki

...the Danube in Austria contained seven antibiotics including clarithromycin, used to treat respiratory tract infections such as pneumonia and bronchitis, at nearly four times the level considered safe. The Danube, Europe’s second-largest river, was the continent’s most polluted.

Eight per cent of the sites tested in Europe were above safe limits.

The Thames, generally regarded as one of Europe’s cleanest rivers, was contaminated, along with some of its tributaries, by a mixture of five antibiotics. One site on the river and three on its tributaries were polluted above safe levels. Ciprofloxacin, which treats infections of the skin and urinary tract, peaked at more than three times safe levels.

Even rivers contaminated with low levels of antibiotics are a threat, Gaze said. “Even the low concentrations seen in Europe can drive the evolution of resistance and increase the likelihood that resistance genes transfer to human pathogens,” he says.

The researchers tested 711 sites in 72 countries and found antibiotics in 65% of them. In 111 of the sites, the concentrations of antibiotics exceeded safe levels, with the worst cases more than 300 times over the safe limit.

Lower-income countries generally had higher antibiotic concentrations in rivers, with locations in Africa and Asia performing worst. They peaked in Bangladesh, where metronidazole, used to treat vaginal infections, was found at more than 300 times the safe level. The residues were detected near a wastewater treatment facility, which in lower-income countries often lack the technology to remove the drugs.

Inappropriate disposal of sewage and waste dumped straight into rivers, as was witnessed at a site in Kenya, also resulted in high antibiotic concentrations of up to 100 times safe levels. “Improving the safe management of health and hygiene services in low-income countries is critical in the fight against antimicrobial resistance,” said Helen Hamilton, health and hygiene analyst at the UK-based charity Water Aid.

The research team is now planning to assess the environmental impacts of antibiotic pollution on wildlife including fish, invertebrates and algae. They expect severe effects. The drug levels in some Kenyan rivers were so high that no fish could survive. “There was a total population crash,” Boxall said...

......................................................................................................

Weedkiller in your breakfast cereal. Contaminated drinking water. Carcinogenic chemicals in your furniture.

Americans are routinely exposed to dangerous chemicals that have long been banned in countries such as the UK, Germany and France. Of the 40,000 chemicals used in consumer products in the US, according to the EPA, only one percent have been tested for human safety.

With support from our readers, The Guardian aims to raise $150,000 for a six-month project on how these levels of toxicity are impacting our lives. We will explore the worrying health implications of living in an environment that can expose us to chemical contamination on a daily basis.

Your support will enable us to examine the power of the $640bn chemical industry – which has a lobby that’s currently better funded than the NRA – and raise public awareness about its influence. This series will help us all to make sense of the complex science and conflicting messages about what’s safe, what’s harmful and what remains unknown...

https://www.theguardian.com/society/2019/may/27/worlds-rivers-awash-with-dangero...

A mechanism by which half-dead bacteria can gain resistance genes even in the presence of antibiotics. :(

How bacteria nearly killed by antibiotics can recover — and gain resistance
Tina Hesman Saey | May 28, 2019

...A protein that pumps toxic chemicals out of E. coli bacterial cells can buy time for even nearly dead microbes to become antibiotic resistant. The protein, known as the AcrAB-TolC multidrug efflux pump, doesn’t work well enough to defeat antibiotics on its own. But it can move enough antibiotic molecules out of bacterial cells to allow production of real resistance proteins...

Bacteria often swap DNA, including some antibiotic-resistance genes. Scientists have known for decades that antibiotic-resistance genes are often carried on small circles of DNA called plasmids. Two bacteria that come in contact with each other can pass these plasmids from antibiotic-resistant cells to sensitive ones. But that was thought to happen when antibiotics aren’t around to kill sensitive cells.

Common wisdom holds that treating bacteria with antibiotics should stop bacteria in the act of swapping antibiotic-resistance genes, says Kim Lewis, a microbiologist at Northeastern University in Boston not involved in the study. At least, “yesterday, that’s what I would have told you,” he says. “Today, having read that paper, I have to change my views.”

...The swaps happen quickly. Within three hours, about 70 percent of sensitive E. coli had become resistant to the antibiotic tetracycline, Lesterlin’s team discovered. When tetracycline was added to the bacteria, about a third of the microbes that were still sensitive also became tetracycline-resistant. “That was very, very surprising,” Lesterlin says.

Once bacteria get the plasmid DNA, they still have to turn on resistance genes and produce the proteins that ultimately fight off antibiotics — in this case a protein called TetA that pumps tetracycline out of bacteria. Tetracycline blocks protein production, so when the drug is around, bacteria that haven’t yet made TetA will be nearly dead and shouldn’t be able to take advantage of newly acquired resistance genes, Lewis says.

But mostly dead bacteria are still slightly alive thanks to the multidrug protein pump — at least enough to sometimes be able to eke out some TetA proteins, which then export all of the antibiotic and eventually return the microbes to full life, the researchers found.

The multidrug pump also helped bacteria stay alive long enough to develop resistance to other antibiotics...

Citations

S. Nolivos et al. Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer. Science. Vol. 364, May 24, 2019, p. 778. doi: 10.1126/science.aav6390 ( https://science.sciencemag.org/content/364/6442/778 ) ...

https://www.sciencenews.org/article/bacteria-nearly-killed-antibiotics-recover-g...

----------------------------------------------------------------------------------------------------------------------------------------

S. Nolivos et al. Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer. Science. Vol. 364, May 24, 2019, p. 778. doi: 10.1126/science.aav6390 https://science.sciencemag.org/content/364/6442/778

A race against time

Clinically relevant antimicrobial resistance is largely spread via plasmids that disperse among bacteria during conjugation. How quickly can a resistance gene be expressed after transfer? In susceptible bacterial cells, tetracycline should inhibit protein synthesis, including from the plasmid-transferred resistance gene tetA. Unexpectedly, Nolivos et al. found that TetA can be expressed despite the presence of tetracycline (see the Perspective by Povolo and Ackermann). Immediately after plasmid transfer into a cell, TetA synthesis starts because its repressor is slow to be expressed. In addition, the ubiquitous xenobiotic efflux pump AcrAB-TolC buys time for TetA translation by keeping tetracycline concentration below toxic levels.

Abstract

Drug-resistance dissemination by horizontal gene transfer remains poorly understood at the cellular scale. Using live-cell microscopy, we reveal the dynamics of resistance acquisition by transfer of the Escherichia coli fertility factor–conjugation plasmid encoding the tetracycline-efflux pump TetA. The entry of the single-stranded DNA plasmid into the recipient cell is rapidly followed by complementary-strand synthesis, plasmid-gene expression, and production of TetA. In the presence of translation-inhibiting antibiotics, resistance acquisition depends on the AcrAB-TolC multidrug efflux pump, because it reduces tetracycline concentrations in the cell. Protein synthesis can thus persist and TetA expression can be initiated immediately after plasmid acquisition. AcrAB-TolC efflux activity can also preserve resistance acquisition by plasmid transfer in the presence of antibiotics with other modes of action...

----------------------------------------------------------------------------------------------------------------------

Vanessa R. Povolo and Martin Ackermann. 2019. Disseminating antibiotic resistance during treatment. Science 24 May 2019: Vol. 364, Issue 6442, pp. 737-738. DOI: 10.1126/science.aax6620 https://science.sciencemag.org/content/364/6442/737

Summary

The spread of antibiotic resistance in bacterial pathogens has become a major public health problem. Resistance genes to clinically relevant antibiotics are often carried on plasmids (circular pieces of DNA) that can be transferred between different types of bacteria through the process of conjugation (1). For example, bacteria that are exposed to antibiotics can survive if they have already received a plasmid with an antibiotic resistance gene from another bacterium. However, how this process of horizontal transfer of resistance genes in the presence of antibiotics works is not entirely clear. Many antibiotics inhibit gene expression, which means that bacteria that have received a plasmid containing an antibiotic resistance gene are unable to express it. On page 778 of this issue, Nolivos et al. (2) describe a mechanism by which bacteria can express resistance genes even in the presence of antibiotics that block gene expression.

https://science.sciencemag.org/content/364/6442/737

Let's not lose this one through misuse--like preventing bovine TB in cows or some other ill-advised venture.

A new FDA-approved drug takes aim at a deadly form of tuberculosis
The antibiotic, paired with two others, works against highly drug-resistant TB
Aimee Cunningham | August 16, 2019

...The U.S. Food and Drug Administration announced August 14 that it has approved the antibiotic pretomanid to help tackle what’s called extensively drug-resistant tuberculosis. This form of the disease is resistant to at least four of the main TB drugs, and treatment often fails: Only around 34 percent of infected patients typically survive...

...The current treatment requires patients to take as many as eight antibiotics orally, and sometimes by injection, for 18 months or more. By contrast, the new antibiotic is paired with two other previously approved drugs, bedaquiline and linezolid, in a six-month course of pills. Ninety-five of 107 patients who had the highly resistant disease and took this drug regimen recovered, according to the TB Alliance, the nonprofit organization that developed pretomanid. The drug is only the third since the 1960s to be approved for tuberculosis, which is caused by Mycobacterium tuberculosis...

Citations

U.S. Food and Drug Administration. FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs. Released August 14, 2019. http://s2027422842.t.en25.com/e/es

...

https://www.sciencenews.org/article/new-fda-approved-drug-takes-aim-deadly-form-...

Post surgery, a cousin picked up a super bug this summer. Fingers crossed, he's out of the woods now, but, having lost an uncle to MRSA it reminds me yet again of antibiotic resistant bugs all around us. Overuse of antibiotics are blamed for spread of antibiotic resistant bugs, but apparently poorly resourced nursing homes with their vulnerable patients are also to blame.

Nursing Homes Are a Breeding Ground for a Fatal Fungus
Matt Richtel and Andrew Jacobs | Sept. 11, 2019

Drug-resistant germs, including Candida auris, prey on severely ill patients in skilled nursing facilities, a problem sometimes amplified by poor care and low staffing...Candida auris, a highly contagious, drug-resistant fungus that has infected nearly 800 people since it arrived in the United States four years ago, with half of patients dying within 90 days.

...Much of the blame for the rise of drug-resistant infections like C. auris, as well as efforts to combat them, has focused on the overuse of antibiotics in humans and livestock, and on hospital-acquired infections. But public health experts say that nursing facilities, and long-term hospitals, are a dangerously weak link in the health care system, often understaffed and ill-equipped to enforce rigorous infection control, yet continuously cycling infected patients, or those who carry the germ, into hospitals and back again.

...Drug-resistant germs of all types thrive in such settings where severely ill and ventilated patients...are prone to infection and often take multiple antibiotics, which can spur drug resistance. Resistant germs can then move from bed to bed, or from patient to family or staff, and then to hospitals and the public because of lax hygiene and poor staffing.

These issues have also vexed long-term, acute-care hospitals, where patients typically stay for a month or less before going to a skilled nursing home or a different facility.

A recent inquiry by the New York State Department of Health found that some long-term hospitals grappling with C. auris were failing to take basic measures, such as using disposable gowns and latex gloves, or to post warning signs outside the rooms of infected patients. At one unnamed facility, it said, “hand sanitizers were completely absent.”

...A study published in June in the Journal of Clinical Infectious Diseases found that patients and residents in long-term care settings have alarmingly high rates of drug-resistant colonization, which means they carry the germs on their skin or in their bodies, usually without knowing it, and can pass them invisibly to staff members, relatives or other patients. Elderly or severely ill people with weakened immune systems who carry the germ are at high risk of becoming infected. (Health officials in New York state said 14 percent of those now infected started out carrying it and then developed symptoms).

...A study published in 2017 found that elderly residents of long-term care facilities in Britain were four times as likely to be infected with drug-resistant urinary tract infections as elderly residents living at home. Soaring levels of resistance were found in long-term care facilities in Italy, a 2018 paper found. And a 2019 study found that long-term care facilities in Israel are “a major reservoir” of carbapenem-resistant Enterobacteriaceae, or CRE — a major family of drug-resistant germs — contributing to their “rapid regional dissemination.”

Experts said the problem is pronounced in the United States, given changing economics that push high-risk patients out of hospitals and into skilled nursing homes. The facilities are reimbursed at a higher rate to care for these patients, they said, providing an economic incentive for poorly staffed or equipped facilities to care for vulnerable patients...

https://www.nytimes.com/2019/09/11/health/nursing-homes-fungus.html

Superbug hotspots emerging in farms across globe – study (Guardian)

Hotspots of antibiotic-resistant superbugs are springing up in farms around the world, the direct result of our overconsumption of meat, with potentially disastrous consequences for human health, a study has found...

10 years ago I lost an uncle to MRSA acquired (after?) surgery. This summer a cousin likewise acquired a Pseudomonas superbug (after?) surgery, but-knock-on-wood-was able to beat it. Who's next?

CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. 148 p. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508...

Foreword

In March 1942, Mrs. Anne Miller of New Haven, Connecticut, was near death.* Infectious germs had made their way into her bloodstream. Desperate to save her, doctors administered an experimental drug: penicillin, which Alexander Fleming discovered 14 years earlier. In just hours, she recovered, becoming the first person in the world to be saved by an antibiotic. Rather than dying in her thirties, Mrs. Miller lived to be 90 years old.

Today, decades later, germs like the one that infected Mrs. Miller are becoming resistant to antibiotics. You could have one in or on your body right now—a resistant germ that, in the right circumstances, could also infect you. But—unlike the bacteria that threatened Mrs. Miller—the bacteria may be able to avoid the effects of the antibiotics designed to kill them.

Unfortunately, like nearly 3 million people across the United States, you or a loved one may face an antibiotic-resistant infection.

This report from CDC, the second of its kind, presents data about the top 18 pathogens that require attention now. It emphasizes that antibiotic resistance is a One Health issue that can spread through people, animals, and the environment; threatens our most vulnerable friends and family members; and affects nearly every aspect of life.

Given the chance, these germs will infect our bodies, take up residence in our healthcare facilities, contaminate our food and water supplies, and move across our communities and around the globe. This report shows us, however, that the fight against antibiotic resistance, no matter how complex, is not hopeless.

U.S. Centers for Disease Control and PreventionviTo stop antibiotic resistance, our nation must:

■Stop referring to a coming post-antibiotic era—it’s already here. You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution.
■Stop playing the blame game. Each person, industry, and country can affect the development of antibiotic resistance. We each have a role to play and should be held accountable to make meaningful progress against this threat.
■Stop relying only on new antibiotics that are slow getting to market and that, sadly, these germs will one day render ineffective. We need to adopt aggressive strategies that keep the germs away and infections from occurring in the first place.
■Stop believing that antibiotic resistance is a problem “over there” in someone else’s hospital, state, or country—and not in our own backyard. Antibiotic resistance has been found in every U.S. state and in every country across the globe. There is no safe place from antibiotic resistance, but everyone can take action against it. Take action where you can, from handwashing to improving antibiotic use.

The problem will get worse if we do not act now, but we can make a difference.

Simply, here’s what works. Preventing infections protects everyone. Improving antibiotic use in people and animals slows the threat and helps preserve today’s drugs and those yet to come. Detecting threats and implementing interventions to keep germs from becoming widespread saves lives.

These actions are protecting us today and will continue to protect us, our families, and our nation from a threat that will never stop. I’m proud to serve alongside the experts who refuse to let this threat disarm us and who are diligently protecting our future by putting science and public health into action. We all have a role to play.

We hope the 2019 AR Threats Report inspires you to act now.

Robert R. Redfield, M.D.
Director, U.S. Centers for Disease Control and Prevention
November 13, 2019

I guess I didn't realize that penicillin was that recent. I was a kindergartener in 1960 and woke one morning with an inner ear infection. I couldn't stand or walk - tipped over sideways. My parents carried me to the doctor's office and I was given a penicillin shot in the butt. Within minutes, I was able to stand and walk normally.

Antibiotic treatment for COVID-19 complications could fuel resistant bacteria
Sara Reardon | Apr. 16, 2020 , 5:05 PM

...Antibiotics do not directly affect SARS-CoV-2, the respiratory virus responsible for COVID-19, but viral respiratory infections often lead to bacterial pneumonia. Physicians can struggle to tell which pathogen is causing a person’s lung problems.

...Hospitals, particularly intensive care units, are hotbeds of antimicrobial resistance, and they have long been struggling to rein in the use of antibiotics. But COVID-19 has put many such efforts on hold. Although the U.S. Centers for Disease Control and Prevention requires medical centers to report their antibiotic use and the rates of infections acquired in the facility, ...compliance has fallen off in the pandemic.

Some researchers suggest the pandemic could slow the spread of both bacteria and antibiotic resistance within hospitals. Surgeries, which account for many hospital-acquired infections, have largely been canceled to keep beds open for COVID-19 patients, and hospital staff routinely wear robes, masks, and other personal protective equipment (PPE) during patient care...But Bo Shopsin, an infectious disease physician at New York University’s Langone Health Center who is involved in DOD’s planned study..."It’s quite clear that COVID is transmitting in hospitals and if it is, resistant bacteria are too.”

More important, antibiotic use appears to be surging. Several recent studies from China suggest that nearly all serious cases of COVID-19 are treated with antibiotics... A recent paper in The Lancet detailing the outcomes of 247 hospitalized COVID-19 patients in Wuhan, China, found that 15% of them—and half of those who died—acquired bacterial infections. Major outbreaks of other respiratory viruses illustrate the concern: up to half the 300,000 people who died of the 2009 H1N1 flu and the majority of deaths from the 1918 flu actually died of bacterial pneumonia.

“We do have some guidelines on when to treat and when not to treat,” says Leopoldo Segal, a pulmonologist at Langone.” But in the current situation, it’s hard to imagine those guidelines are totally applicable.” Several of his COVID-19 patients, he says, have antibiotic-resistant infections, and nearly all are receiving azithromycin: a widely used antibiotic that kills both of the two major classes of bacteria.

...President Donald Trump and others highlighted small, uncontrolled studies that appeared to show the ( hydroxychloroquine, azithromycin) combination was effective...prescribed (often )...enough to have caused an azithromycin shortage in the United States.

...in some parts of the United States, 30% to 40% of some common types of bacteria were already resistant to the class of drugs that includes azithromycin, and overuse could render those or other antibiotics even less effective.

The DOD study will investigate just how widely antibiotics are being given to COVID-19 patients, and how often they have secondary infections that warrant antibiotic use...should help experts develop guidelines...

https://www.sciencemag.org/news/2020/04/antibiotic-treatment-covid-19-complicati...

>55 2wonderY: Around the same time I came down with scarlet fever. I was given one shot (as viscous as jello) and two pills a day for two weeks. I learned how to swallow pills because they were the most bitter thing I ever put in my mouth. Luckily I never acquired an allergy to penicillin though they don't seem to use it any more.

>56 margd: contd.

Doctors Heavily Overprescribed Antibiotics Early in the Pandemic
Now they are using lessons from the experience to urge action on the growing problem of drug-resistant infections before it’s too late.
Andrew Jacobs | June 4, 2020

...Many critically ill patients on ventilators have developed serious secondary infections. But widespread fears that coronavirus patients were especially susceptible to drug-resistant infections — a concern first described in studies from China — appear to have been misguided, according to interviews with researchers and more than a dozen doctors who have been treating patients with Covid-19...

...“If there’s anything that this Covid-19 pandemic has taught the world, it is that being prepared is more cost-effective in the long run,” said Dr. Jeffrey R. Strich, a researcher at the National Institutes of Health Clinical Center and an author of a study* published on Thursday in Lancet Infectious Diseases that seeks to quantify the growing need for new antibiotics to treat drug-resistant infections. “Antimicrobial resistance is a problem we cannot afford to ignore.”...

https://www.nytimes.com/2020/06/04/health/coronavirus-antibiotics-drugs.html

____________________________________________________

* Jeffrey R Strich et al. 2020. Needs assessment for novel Gram-negative antibiotics in US hospitals: a retrospective cohort study. The Lancet Infectious Diseases. Published:June 04, 2020DOI:https://doi.org/10.1016/S1473-3099(20)30153-5 https://www.thelancet.com/journals/lancet/article/PIIS1473-3099(20)30153-5/fullt...

Summary

Background
Evidence-based needs assessments for novel antibiotics against highly-resistant Gram-negative infections (GNIs) are scarce. We aimed to use real-world data from an electronic health record repository to identify treatment opportunities in US hospitals for GNIs resistant to all first-line drugs.

Methods

Findings

Interpretation
Suspected or documented GNIs with no or suboptimal treatment options are relatively infrequent. Non-revenue-based strategies and innovative trial designs are probably essential to the development of antibiotics with improved effectiveness for these GNIs.

Funding

Blue light must be the only thing doctors didn't try to help my poor uncle in his losing battle with MRSA, which had invaded his shoulder joint... (Didn't Trump propose something like this for COVID-19?? Dangerous UV, though, not blue light...)

Blue light may be the key to defeating MRSA
Robby Berman on June 4, 2020

Scientists in Boston, looking into new optical microscope techniques, have unexpectedly been able to break down MRSA’s surrounding membrane, using blue light.

A blue light laser can kill MRSA without affecting healthy cells...

https://www.medicalnewstoday.com/articles/blue-light-may-be-the-key-to-defeating...
__________________________________________________________________

Jie Hui et al. 2020. Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA. Advanced Science. First published: 27 January 2020. https://doi.org/10.1002/advs.201903117 https://onlinelibrary.wiley.com/doi/10.1002/advs.201903117

Abstract
Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug‐resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin‐resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo‐disassembly of functional membrane microdomains. The photo‐disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore‐targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug‐resistant S. aureus infections as well as to screen new lead compounds.

>48 margd: National TV in Holland had an item about the use of bacteriophages against resistant bacteria. This therapy is over a hundred years old, and widely used in Tbilisi, Georgia.
It seems to work well, but can't be used, at least not in Holland, because of regulations.

Interesting article in The Lancet giving more information:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)66759-1/fullt...

"Our machine learning decision algorithm provides antibiotic stewardship for a common infectious syndrome (UTIs) by maximizing reductions in broad-spectrum antibiotic use while maintaining optimal treatment outcomes."

Sanjat Kanjila et al. 2020. A decision algorithm to promote outpatient antimicrobial stewardship for uncomplicated urinary tract infection. Science Translational Medicine 04 Nov 2020: Vol. 12, Issue 568, eaay5067 DOI: 10.1126/scitranslmed.aay5067 https://stm.sciencemag.org/content/12/568/eaay5067

Abstract
Antibiotic resistance is a major cause of treatment failure and leads to increased use of broad-spectrum agents, which begets further resistance. This vicious cycle is epitomized by uncomplicated urinary tract infection (UTI), which affects one in two women during their life and is associated with increasing antibiotic resistance and high rates of prescription for broad-spectrum second-line agents. To address this, we developed machine learning models to predict antibiotic susceptibility using electronic health record data and built a decision algorithm for recommending the narrowest possible antibiotic to which a specimen is susceptible. When applied to a test cohort of 3629 patients presenting between 2014 and 2016, the algorithm achieved a 67% reduction in the use of second-line antibiotics relative to clinicians. At the same time, it reduced inappropriate antibiotic therapy, defined as the choice of a treatment to which a specimen is resistant, by 18% relative to clinicians. For specimens where clinicians chose a second-line drug but the algorithm chose a first-line drug, 92% (1066 of 1157) of decisions ended up being susceptible to the first-line drug. When clinicians chose an inappropriate first-line drug, the algorithm chose an appropriate first-line drug 47% (183 of 392) of the time. Our machine learning decision algorithm provides antibiotic stewardship for a common infectious syndrome by maximizing reductions in broad-spectrum antibiotic use while maintaining optimal treatment outcomes. Further work is necessary to improve generalizability by training models in more diverse populations.

Madhu Pai, MD, PhD (McGill U) @paimadhu | 7:40 AM · May 22, 2021:
Still thinking about Prof @spkalantri 's words yesterday:
they are seeing hospital-associated infections (e.g. A. baumannii *) which are completely untreatable.

Covid-19 +
antimicrobials +
immuno-suppressives +
overwhelmed health system =
Antimicrobial resistance, the next wave
--------------------------------------------------------

* Acinetobacter is a group of bacteria (germs) commonly found in the environment, like in soil and water. While there are many types, the most common cause of infections is Acinetobacter baumannii, which accounts for most Acinetobacter infections in humans.

Acinetobacter baumannii can cause infections in the blood, urinary tract, and lungs (pneumonia), or in wounds in other parts of the body. It can also “colonize” or live in a patient without causing infections or symptoms, especially in respiratory secretions (sputum) or open wounds.

These bacteria are constantly finding new ways to avoid the effects of the antibiotics used to treat the infections they cause. Antibiotic resistance occurs when the germs no longer respond to the antibiotics designed to kill them. If they develop resistance to the group of antibiotics called carbapenems, they become carbapenem-resistant. When resistant to multiple antibiotics, they’re multidrug-resistant. Carbapenem-resistant Acinetobacter are usually multidrug-resistant...

https://www.cdc.gov/hai/organisms/acinetobacter.html

___________________________________________

Perez S, Innes GK, Walters MS, et al. Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions — New Jersey, February–July 2020. MMWR Morb Mortal Wkly Rep 2020;69:1827–1831. DOI: http://dx.doi.org/10.15585/mmwr.mm6948e1 https://www.cdc.gov/mmwr/volumes/69/wr/mm6948e1.htm

____________________________________________

Deadly Fungi Are the Newest Emerging Microbe Threat All Over the World
These pathogens already kill 1.6 million people every year, and we have few defenses against them
Maryn McKenna | June 1, 2021

75,000 people in the U.S. are hospitalized by fungi every year. 8.9 million are seen as outpatients

Estimated fungal species: 5 million. Number known to cause human disease: 300

https://www.scientificamerican.com/article/deadly-fungi-are-the-newest-emerging-...

...a (single) letter (to high-prescribing primary care physicians) targeting appropriate antibiotic durations resulted in a statistically significant 4.8% relative reduction in total antibiotic use...

Kevin L. Schwartz et al. 2021. Effect of Antibiotic-Prescribing Feedback to High-Volume Primary Care Physicians on Number of Antibiotic Prescriptions: A Randomized Clinical Trial. JAMA Intern Med. Published online July 6, 2021. doi:10.1001/jamainternmed.2021.2790

Key Points
Question Does providing a single, mailed, peer-comparison letter on antibiotic use to high-prescribing primary care physicians targeting either initiation or duration of antibiotic treatment modify prescribing behavior?

Findings In this randomized clinical trial of 3500 primary care physicians in Ontario, Canada, receipt of a letter targeting appropriate antibiotic durations resulted in a statistically significant 4.8% relative reduction in total antibiotic use.

Meaning A single, peer-comparison, antibiotic-feedback letter to high-prescribing physicians can be effective and cost saving, especially if it includes targeted messaging on appropriate durations of antibiotic prescriptions.

Using data from thousands of patients with wound infections and urinary tract infections, researchers in Science built a new machine learning approach that can predict and minimize risk of treatment-induced antibiotic resistance.

Mathew Stracy et al. 2022. Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections. Science • 24 Feb 2022 • Vol 375, Issue 6583 • pp. 889-894 • DOI: 10.1126/science.abg9868 https://www.science.org/doi/10.1126/science.abg9868

Personal histories of past resistance
A serious infection may initially be diagnosed as antibiotic susceptible but subsequently become drug resistant—and life threatening. Rather than de novo resistance mutation occurring, it is more likely that a resistant strain or species persisting in the patient’s gut or skin replaced the susceptible strain. From this starting point, Stracy et al. built machine-learning models that predict individual risks of gaining resistance to specific antibiotics using 8 years of records on more than 200,000 patients’ microbiome profiles (see the Perspective by Lugagne and Dunlop). Data on antibiotic use for urinary tract and wound infections were used to train the algorithms and to develop personalized antibiotic treatment strategies. For most patients, there was an alternative susceptibility-matched antibiotic that had a lower predicted risk of resistance emerging compared with the antibiotic prescribed by the physician. —CA

Andrew Oliver et al. 2022. Association of Diet and Antimicrobial Resistance (AMR) in Healthy U.S. Adults. mBio 10 May 2022. DOI: https://doi.org/10.1128/mbio.00101-22 https://journals.asm.org/doi/10.1128/mbio.00101-22

ABSTRACT
...we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h ASA24® tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG (antibiotic resistant genes)) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR.

...DISCUSSION
...In conclusion, we report that a diverse cohort of healthy individuals harbor significant variability in their resistomes.* We show that ARG ((antibiotic resistant genes)) diversity was associated with diversity in diet and the microbiome. Specifically, we showed that individuals with lower abundances of antibiotic resistance genes consumed more diverse diets that were richer in fiber and limited in animal protein. We suspect that increased fiber likely drives the composition of the gut toward a more obligate anaerobe state, reducing footholds for facultative anaerobes, which are known harbors of inflammation and antibiotic resistance. Critical next steps include assessing SCFA (short chain fatty acid metabolism more directly to better determine whether high-fiber diets contribute to microbial communities intrinsically lower in antibiotic-resistant genes. Ultimately, future work may use research-based dietary guidelines to reduce the incidence of antimicrobial resistance, thus lifting an immense burden on health care systems worldwide.

* (resistomes) In humans, antimicrobial resistance is harbored in the microbiome, where microbes carry genetically encoded strategies to survive contact with antibiotics. The collection of these genes is known as the human resistome. The human resistome varies, in part, as a function of lifestyle. For example, individuals living in rural societies (i.e., nonindustrialized societies) with no access to modern medicine..., and even ancient humans ..., show evidence of abundant and diverse reservoirs of antibiotic resistant genes... within fecal metagenomes even though these populations were not exposed to modern antibiotics. Regardless, the composition and diversity of ARGs ((antibiotic resistant genes)) in industrialized populations are significantly different from nonindustrialized populations.... One explanation for differences in antimicrobial resistance profiles could be differences in diet...

Willem van Schaik @WvSchaik | 7:50 AM · Oct 15, 2022:
Director of @IMIBirmingham. Prof of Microbiology and Infection: microbial genomics, metagenomics & evolution of antibiotic resistance.

This is a spectacularly idiotic plan. Providing antibiotics without prescription creates a major public health risk and will not lead to any savings, as more resistant infections will need treatment (and those are expensive)
....................................................

Patients will be able to obtain antibiotics from pharmacies without seeing a doctor under new plans aimed at reducing the need for GP appointments

...Although (Thérèse Coffey, the health secretary) is not considering making antibiotics available over the counter, (s)he is planning a Scottish-style scheme that would allow pharmacists to prescribe antibiotics, without the advice of a doctor, to patients they believe are suffering from certain conditions.

...Coffey had to be convinced by Chris Whitty, the chief medical officer, that the rise of antibiotic resistant superbugs was a significant problem, after suggesting at the start of her tenure that the drugs should be made far easier to obtain in order to free up doctors...

https://www.thetimes.co.uk/article/chemists-to-prescribe-antibiotics-under-coffe...

Increasing Threat of Spread of Antimicrobial-resistant Fungus in Healthcare Facilities (Press Release)
CDC | March 20, 2023

Candida auris (C. auris), an emerging fungus considered an urgent antimicrobial resistance (AR) threat, spread at an alarming rate in U.S. healthcare facilities in 2020-2021, according to data from the Centers for Disease Control and Prevention (CDC) published in the Annals of Internal Medicine. Equally concerning was a tripling in 2021 of the number of cases that were resistant to echinocandins, the antifungal medicine most recommended for treatment of C. auris infections. In general, C. auris is not a threat to healthy people. People who are very sick, have invasive medical devices, or have long or frequent stays in healthcare facilities are at increased risk for acquiring C. auris. CDC has deemed C. auris as an urgent AR threat, because it is often resistant to multiple antifungal drugs, spreads easily in healthcare facilities, and can cause severe infections with high death rates...

https://www.cdc.gov/media/releases/2023/p0320-cauris.html
_________________________________________________

Deadly Fungi Are the Newest Emerging Microbe Threat All Over the World
These pathogens already kill 1.6 million people every year, and we have few defenses against them
Maryn McKenna | 1 June 2021
https://www.scientificamerican.com/article/deadly-fungi-are-the-newest-emerging-...

>67 margd: I first heard about this years ago. Systematic candida infections are dangerous, difficult to identity with the limited resources many medical facilities are using, and challenging to treat. I think the drug that's usually prescribed is also getting harder for patients to get because of politics.

Medical facilities should have started set up regular testing immediately. The federal and state governments should be supporting research and proven safety regulations. But that's like saying accessible healthcare should be a priority in the USA.

We know this is going to spread, disabling and killing people, because not enough people care enough.

So much we could be doing... Incredible that factory farms are still using antibiotics as prophylactics, that we are so slow to address clean air in our buildings...

Wonder if Supreme Court's Chevron decision could be put to good use here?

Sen Booker takes aim at proposed FDA guidance on agricultural antibiotics
Stephanie Soucheray | 12 July 2024

US Senator Cory Booker (D-NJ) sent a letter* to the Food and Drug Administration (FDA) that highlights concerns about revisions to FDA guidance on duration limits for antibiotic use in farm animals.

Booker is concerned about revisions to Guidance for Industry #152 (GFI#152) and draft Guidance for Industry #273 (draft GFI#273), which would eliminate a 21-day limit for medically important antimicrobials and instead allow the duration of use to be set on a case-by-case basis. Booker said that policy would contribute to antimicrobial resistance (AMR)...

https://x.com/CIDRAP/status/1811799567144263715
---------------------------------------

3p letter from Sen Booker to FDA Commissioner:

I ask that you answer the following questions.
1. Does the FDA believe it is appropriate to make human safety decisions based on animal health needs--as it has done in its revisions to GFI#152 and GFI#273--for durations of use intended to protect human health?
2. How will the FDA’s consideration of animal health concerns impact its ability to ensure human safety in the use of animal drugs? Will FDA now begin to consider animal health or economic benefit to the impacted industry when holding hearings on whether to withdraw drugs from the
market for safety reasons?
3. Does the FDA believe it has the authority to ask drug sponsors to voluntarily adopt durations that are consistent with existing guidance (i.e. under 21 days as recommended by the original GFI#152)? If not, please explain why the FDA does not have authority for requesting this
voluntary action.
4. Given the slow pace of action to address the critical public health threat of antibiotic resistance, what additional resources or authorities does the FDA need to take prompt action to protect public health from antibiotic resistance?
5. It has been over 20 years since the Interagency Task Force on Antimicrobial resistance identified collection of antibiotic use data as a priority.
6a. When does the FDA anticipate creating “functional and efficient systems for collecting antimicrobial use data in animals” as described ... in the FDA’s 2019-2023 plan for antimicrobial stewardship in veterinary settings? When does the FDA expect the data collection plan to be finalized, and when will it be implemented?
b. So far, the FDA has only publicly discussed a public-private partnership.
i. Why has the FDA not collected feed distribution data from feed mills as
recommended by public health advocates?...
ii. What resources would be needed to collect drug distribution data from feed mills?
iii. How would the resource needs for collecting feed distribution data compare to resource needs for collecting data through a public-private partnership?
iv. If the FDA does move forward with a public-private partnership how will the agency ensure that the collected data is representative i.e., how will it ensure that those facilities practicing poor antimicrobial stewardship (that will likely not beinclined to participate) are represented?
6. What is the FDA doing to measure its progress on combating antibiotic resistance? Has the FDA adopted any indicators of success such as a reductions in antibiotic use by livestock sectors and reductions in antibiotic resistance in food animal isolates?