The state of antibiotic resistance in the US and Canada

Issue 52 | November 15, 2019
14 min read
Capsid and Tail

Images courtesy of the CDC and CCA

This week, we provide an overview of two major new antibiotic resistance reports: one from the US (CDC) and one from Canada. We provide a few takeaways, briefly compare the reports, and hope to inspire you to dive in to learn more about the magnitude of the antibiotic resistance problem.

Also in this issue: phages for liver diseases, phage libraries available for compassionate use, FDA approves Intralytix using its phages on ground beef, a phage therapy panel in India, and more!

What’s New

Yi Duan (UCSD) and colleagues have published an incredibly exciting paper showing that cytotoxin-secreting Enterococcus faecalis in the mouse gut is a cause of alcohol-induced liver disease in mice. Most excitingly, they used phages to target cytotoxin-positive E. faecalis, and found that this abolished alcohol-induced liver disease in the mice! This is a great example of what microbiome-editing could look like, and shows the potential promise of phages (next step: testing this in humans). Paper | Commentary by Martha Clokie

Liver diseaseResearchPhage TherapyMicrobiome editing

Shelley Gibson (Baylor College of Medicine) and colleagues have published a paper describing the generation of phage libraries against three pathogens: E. coli, P. aeruginosa and Enterobacter cloacae. They’ve characterized the phages systematically, including evaluating their potency against clinical strains. All phages are now available for compassionate use.

Phage libraryResearchPhage Therapy

Diane Shader Smith wrote a beautiful article commemorating the two-year anniversary of her daughter Mallory’s passing. Mallory passed away due to drug-resistant Burkholderia and cystic fibrosis. Diane remarks that Mallory’s legacy lives on both through her writing and through phage therapy, which might have saved her if she’d had more time. Mallory’s father Mark envisions a day where kids with CF can receive phage therapy before infections destroy their lungs. The Smith family made the inaugural donation to UCSD’s IPATH in 2018.

In memoryPhage TherapyCystic Fibrosis

BiomX just presented preclinical data on its development of a phage cocktail active against Klebsiella pneumoniae strains correlated with primary sclerosing cholangitis (PSC) severity. PSC is a liver disease with no FDA-approved treatment that affects 30,000 US patients.

BiotechPhage TherapyPreclinical dataPhage cocktail

One of Intralytix’s phage products, EcoShield (which targets E. coli O157:H7), has been approved by the FDA to be used more broadly. Now it can be used on ground beef (plus other meat cuts and on carcasses). Previously, it could only be used on parts and trim prior to grinding or packing.

BiotechPhages in foodRegulation

The Open Health Systems Colloquium and the International Bacteriophage Research Consortium will be hosting a lecture and panel discussion on “Charting a Path Toward Bacteriophage Therapy” on Nov. 19 from 6-8:30 PM at the India International Centre in New Delhi, India. Panelists: Steffanie Strathdee, Tom Patterson, Biswajit Biswas, Sanjay Chhibber; moderator: Urmi Bajpai. Watch the live webcast here!

PanelPhage TherapyLive stream

Edze Westra of the University of Exeter has been awarded the 2020 Fleming Prize from the Microbiology Society for his work on CRISPR-CAS molecular mechanisms and evolutionary ecology. This award is the oldest prize awarded by the Microbiology Society (which was founded by Sir Alexander Fleming himself!).

AwardMicrobiologyCRISPR

Latest Jobs

Research scientist, Intralytix

Intralytix, Columbia, Maryland

Intralytix is currently seeking an experienced Research Scientist to work at our laboratories. The successful candidate will participate in various research projects focused on the development of bacteriophage-based products, with a focus on human health applications. This is a hands-on bench-based position and requires proficiency in microbiology and molecular biology techniques. The salary and position level will be commensurate with experience and qualifications. The benefits package includes health insurance, company paid life insurance and long-term disability insurance, paid parking, and 401(K) with matching company contribution.

Scientist Human healthPhage product development

Postdoctoral position: Pediatrics/Emerging Pathogens

Eric Nelson, MD PhD, University of Florida

A postdoctoral research position is available in the laboratory of Eric Nelson MD PhD at the Emerging Pathogens Institute, University of Florida. The overall goal of our laboratory is to develop better methods to improve the care, diagnosis and management of patients during large-scale diarrheal disease outbreaks. Our model system is cholera and our primary collaborative field sites are in Bangladesh and Haiti. In the field, our research focuses on identifying and characterizing key selective pressures that drive disease severity and transmission. At the University of Florida, we test hypotheses derived from the field studies in animal models of infection and transmission.

The current available project lies at the physiologic interface between host and pathogen. Specifically, the first phase of research involves characterizing the microbiota of human diarrheal disease samples and identifying antimicrobial factors important to pathogenesis and transmission (e.g. antibiotics by LC/MS and bacteriophage).

Post Doc PediatricsVibrio cholerae

Scientist, MilliporeSigma

MilliporeSigma, Bedford, MA

MilliporeSigma is seeking a Scientist for our Virology and Microbiological Sciences Team. This is a hands-on laboratory position to help new product development and optimize performance of current products for MilliporeSigma customers.

This position will be responsible for the following: perform virus titer assays using infectivity, qPCR and plaque enumeration; prepare and characterize stocks of bacteriophage and mammalian viruses; execute filtration and chromatography studies to characterize virus retention characteristics of membranes and resins; execute virus inactivation studies; contribute to method development and validation; preparation of test methods and reports.

Scientist VirologyBioprocessing

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

November 12, 2019

Seeking Post Doctoral Research Fellowship

My name is Dr. Adamu Kaikabo Ahmad, currently working at National Veterinary Research Institute Vom, Nigeria. I hold a degree in Veterinary Medicine, and Master degree in Veterinary Science. I obtained my PhD in Bacteriology and Food Safety in 2016. My PhD thesis was on phage therapy against colibacillosis in chickens, an infection caused by avian pathogenic Escherichia coli (APEC). I’ve isolated and characterized numerous phages against E. coli, Riemerella anatipestifer, Aeromonas hydrophila. Looking for a postdoctoral position. Contact karkafa@yahoo.co.uk.

Seeking opportunity
November 15, 2019

Boston PFU (Phage Fanatics United) First Meetup!

Boston PFU

The first meeting of Boston PFU (Phage Fanatics United) will be Thursday, Dec. 5, 2019 at the Countway Medical Library, Harvard Medical School. Find details and join the mailing list here! This is a social and general meeting, and is open to anyone interested in phages. Email bostonpfu@gmail.com with any questions.

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The state of antibiotic resistance in the US and Canada

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Phage microbiologist and co-founder of Phage Directory
Co-founder
Phage Directory, Atlanta, GA, United States

Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology from the University of Alberta.

For Phage Directory, she takes care of the science, writing, communications, and business aspects.

Within the last week, not one but TWO major national antibiotic resistance reports were released. One was produced by the Centers for Disease Control and Prevention (CDC), and covers the burden of antibiotic resistance in the US. The other was commissioned by the Government of Canada and written by a panel of independent, multidisciplinary experts to give an outlook on this burden in Canada.

Read the reports here:

Great examples of clear writing and data visualization

This post is not meant to summarize the entire contents of the reports; they are both choc-full of fascinating data and beautiful visuals, and are extremely clearly written and easy to read. I’ve only scratched the surface with this article, and highly recommend you have a look through the actual reports, take time to understand the findings, and refer back to them over time as references. (And of course, use them as a rich new source of figures to borrow for your intro powerpoint slides…).

At a glance: what’s in the reports?

Both reports tally deaths attributed to antibiotic resistance, and provide detailed breakdowns of what kinds of infections and syndromes are causing the problems. The Canadian report gets more into estimating how much antibiotic resistance is costing Canadians (and how much it is predicted to cost in the future). The CDC report talks more about kinds of bacteria causing the most risk, and which ones they’ve been able to curb. Both reports emphasize that antibiotic resistance is a global public health crisis second only to climate change. And yet, the reports do include positive stories of the progress that’s been made in recent years.

When was the last time reports like these were released?

The CDC’s last report was released in 2013. The Canadian report is the first of its kind in Canada. The UK released a similar report in 2016, which has been widely referenced around the world (most of us have probably heard the estimate that by 2050, AMR will cause 10 million deaths per year (more than cancer); this estimate came from that report).

Resistance-attributed deaths per year

According to the CDC report, the current rate for resistance-attributed deaths in the US is 35,000 deaths/year. The CDC report also, separately, counts deaths from C. difficile infections (around 12,800/year). The Canadian report shows a rate of 14,000 resistance-attributed deaths/year (with 5,400/year, or about 15/day, directly attributed to resistance).

CDC reports a reduction in deaths since 2013 (though the numbers don’t look that way at first)

Of note, the 2013 CDC report showed 23,000 deaths/year, which makes it look like death rates have gone up since then. However, they state in their report that they had access to more data sources this year, so they recalculated the 2013 values using these sources. They found that they underestimated the numbers in 2013 by around two-fold.

The revised 2013 estimate is 44,000 deaths/year, showing a decrease from then to now (down to 35,000/year). This is of course good news, but this number is still too high. Plus, resistance burden is about more than number of deaths (e.g. costs of care, decreased quality of life, loss of limbs, adverse drug events, etc. all contribute to the burden of resistance).

Overall, the CDC report states that the burden of antibiotic resistance threats in the US is actually greater than initially understood, even though they’ve seen a reduction in deaths.

Costs of antibiotic resistance

The Canadian report showed results of modeling based on “micro-costing” to estimate direct costs of antibiotic resistance.

For example, in 2018, antibiotic resistance led to:

  • $2 billion reduction in Canada’s GDP
  • $1.4 billion in costs to the Canadian healthcare system
  • Average cost of resistance per patient: $18,000

And by 2050:

  • Canada’s GDP is estimated to be reduced by $13-21 billion per year
  • Canada’s animal farming industry is estimated to lose $26-37 billion per year

The CDC report provided costs per pathogen for many pathogens, but did not provide total resistance costs on a national scale. However, the numbers are staggering even for individual pathogens (for example, Candida species alone cause $3 billion in direct medical costs per year in the US, already dwarfing the costs for all of Canada’s resistant infections combined).

Predominant pathogens and syndromes

The CDC report provides in-depth analysis, pathogen by pathogen, of cases over time, types of infection, methods of treatment, and more. It divides them into urgent, serious, and concerning threats, and has a new “watch list” for pathogens newly classified as important to watch.

Urgent threats (highest threat level), according to CDC:

  • Carbapenem-resistant Acinetobacter
  • Candida auris
  • Clostridioides difficile
  • Carbapenem-resistant Enterobacteriaciae
  • Drug-resistant Neisseria gonorrhoeae

By contrast, the Canadian report stated it lacked the surveillance data to examine resistant infections on a pathogen by pathogen basis, so it instead focused more on 10 bacteria-induced clinical syndromes.

These syndromes accounted for 91% of hospital costs associated with resistance in Canada:

  • Skin and soft tissue infections
  • Urinary tract infections
  • Pneumonia
  • Intra-abdominal infections

Proposed solutions

Both reports mentioned that surveillance, prevention (e.g. antibiotic stewardship and hygiene) and new therapeutics (vaccines, phages, etc) are paramount. Both reports emphasize that antibiotic resistance is a One Health problem that needs to be addressed by making changes in human, animal and environmental health. They also both emphasize that antibiotic resistance is a global problem, as bacteria cross borders easily, so it’s important to see this as a constantly-evolving problem (even if it’s solved here, resistant bugs from other regions will keep coming in since people are always traveling).

Is phage therapy discussed in the reports?

Yes, both reports described phage therapy as a possible antibiotic alternative. Each report used the word “phage” 12 times in the main text. By comparison, the reports used the word “vaccine” (or variations of the word) 45-50 times. While considered somewhat cautiously in both reports, phage therapy was far from being an afterthought, and seemed to be portrayed as a serious option by both.

Any good news?

It’s of course good news that these reports are coming out at all. As well, the CDC report showed evidence for how surveillance, prevention, stewardship, and interventions can work, and showed a number of areas where the US made progress since 2013. For example, children’s outpatient antibiotic prescriptions have come down by 16%, and vancomycin-resistant Staphylococcus aureus has been removed as a threat. There’s a nice table in the CDC report showing all the bacterial pathogens that have increased or decreased in prevalence in patients since the 2013 report was published, and several have actually shown a decrease.

The Canadian report also highlights infection prevention and control programs that have made a difference thus far, and points to a nation-wide action plan that will come out next year, which will be informed in part by the results of the Canadian report.

Read the reports here:

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