New Lab Matters: A game-changer in the fight against antibiotic resistance

New Lab Matters (cover): A game-changer in the fight against antibiotic resistance

Given the global rise of drug-resistant pathogens over the past few decades, some physicians and scientists warn of a possible antibiotic apocalypse—a scary, post-antibiotic era. But a $160 million CDC effort now aims to keep antibiotic resistance rare. And as our feature article shows, the “game-changing” keystone of this effort is the Antibiotic Resistance Laboratory Network.

Here are just a few of this issue’s highlights:

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Are antibiotics making printers great…again?

Are antibiotics making printers great...again? | www.APHLblog.org

By Eric Ransom, APHL-CDC Antimicrobial Resistance Fellow

Let’s be honest: printers have never been that great. These frustrating devices turn what should be a simple office task into a game of chance. Is there paper? Did it jam? Can I get by without replacing the toner cartridge… again? Ugh! I personally cannot wait until this archaic technology sails off into the sunset. Goodbye frustration and hello forestation.

You can imagine my surprise when I heard a PRINTER could help fight one of the most significant public health threats of our time: antibiotic resistance. That’s right. The end of the antibiotic era looms, but hope lies with a printer!

To be fair, this is not your ordinary printer that puts ink to paper. This is a bioprinter that “prints” antibiotics! The technology ultimately helps clinicians decide which antibiotic is most likely to be effective in treating an infection. Prescribing the proper antibiotic is key to saving lives today and preserving antibiotics for tomorrow.

More specifically, the bioprinter makes antibiotic panels for broth microdilution susceptibility testing, a gold-standard method in clinical and public health microbiology. To make an antibiotic panel, the bioprinter dispenses minuscule amounts of antibiotics into a 96-well plate containing liquid that supports microbial growth. Microbiologists can then add a patient’s microbe to the plate and observe which antibiotic (or combination of antibiotics) inhibits growth. If an antibiotic inhibits growth on the plate, chances are good that it will also inhibit growth in the person. Results are shared with clinicians so they can prescribe the best antibiotic(s) to treat the infection. What makes the bioprinter unique is that it can easily make antibiotic plates with complex antibiotic combinations and new-to-market antibiotics. The latter is especially exciting given it can take years before new-to-market antibiotics are included on commercially available plates and systems found in most hospital laboratories.

In 2018, the Centers for Disease Control and Prevention announced a pilot program to implement the bioprinter technology in the Antibiotic Resistance Laboratory Network, a consortium of 56 public health laboratories that aims to rapidly detect and respond to antibiotic resistance. The pilot program already uses the bioprinter to offer expanded antibiotic susceptibility testing for hard-to-treat infections in four public health laboratories: Wisconsin State Laboratory of Hygiene, Minnesota Department of Health Public Health Laboratory, Wadsworth Center Laboratories and Tennessee State Public Health Laboratory. This susceptibility testing is free, compliant with patient testing regulations, and available for all qualifying isolates from any hospital laboratory. The testing is also performed within three working days to quickly assist clinicians with therapeutic management.

The pilot program has already begun susceptibility testing with a new drug combination (aztreonam-avibactam) against Enterobacteriaceae producing a metallo-β-lactamase (MβL). These are some of the most resistant microbes, and there are very few effective treatment options. To qualify for this particular testing, isolates must be non-susceptible to all current β-lactam antibiotics (including either ceftazidime-avibactam or meropenem-vaborbactam). Moving forward, the pilot program will expand testing to include other highly resistant microbes and new-to-market antibiotics.

So how exactly does the bioprinter pilot program work in practice? Let’s say a hospital patient has symptoms of a serious infection. Samples from the patient are tested in the hospital’s laboratory to identify the responsible microbe and to determine possible treatment options. If the microbe is found to be highly resistant and clinicians are in need of additional treatment options, the microbe is sent to one of the four public health laboratories piloting the bioprinter program. Microbiologists there can use the bioprinter to print plates for testing the newest antibiotics to see what, if any, are effective in treating the patient’s infection. Results are then returned to clinicians where the patient is being treated.

Implementation of the bioprinter in the AR Lab Network has the potential to be truly impactful. First, clinicians are given a resource to find new, effective treatment options for their patients’ most resistant infections. Second, compiled data from this pilot program can be used to improve antibiotic prescribing, capture national antibiotic efficacy, help establish antibiotic breakpoints and even inform infection control and prevention practices.

The bioprinter pilot program is a remarkable step forward in the fight against antibiotic resistance. It is important to realize though that this crisis still requires comprehensive long-term intervention including discovery of new antibiotics, development of new diagnostics, and an unequivocal commitment to antibiotic stewardship in healthcare and beyond. In the short term, though, a printer might just be exactly what the doctor ordered.

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Improved search makes it easier to find antimicrobial resistance protein information

It’s now easier to find known antimicrobial resistance (AMR) protein information at NCBI. You can search by gene symbol, protein name, or accession across NCBI databases and retrieve the best representative DNA sequence that is a reference for antimicrobial resistance … Continue reading

Track pathogenic organisms promptly with the National Database of Antibiotic Resistant Organisms

In response to the rising threat of antimicrobial resistance (AMR), NCBI built the National Database of Antibiotic Resistant Organisms (NDARO). With NDARO, you can: Browse a curated database of AMR genes Identify AMR genes in bacterial genomes with AMRFinder Identify bacterial … Continue reading

Responding to Emerging and Zoonotic Infectious Disease Threats in 2017

Montage of photos. From left: a photo of different raw foods, including salmon, fruits and vegetables. A photo of a boy taking an oral vaccine. A photo of bacteria growing in petri dish.

Photo of Rima F. Khabbaz, MD, Director, National Center for Emerging and Zoonotic Infectious Diseases
Rima F. Khabbaz, MD, Director, National Center for Emerging and Zoonotic Infectious Diseases

The fungal superbug Candida auris causes serious and often fatal infections. It can strike people in the places where they seek care—hospitals and other healthcare facilities. In early 2016, we knew about outbreaks of C. auris infections on multiple continents, but we were not sure whether C. auris was in the United States. Fast forward to 2017: C. auris is a priority for public health workers in the United States, and CDC, along with state and local health departments, has tracked more than 200 cases of C. auris infection in the country. Our experts have worked with healthcare facilities across the nation to implement infection control measures and stop transmission.

The progress to track and prevent C. auris is just one example of the important work experts from CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) tackled in 2017. Some of the other highlights from the NCEZID 2017 Accomplishments report are described below.

A tremendous year for public health

Summarizing last year’s major efforts was a difficult task. The numbers alone depict a tremendous year for public health. Here are just a few examples.  CDC sequenced nearly 45,000 DNA samples by using Advanced Molecular Detection (AMD) technologies. The agency identified more than 1,100 illnesses that were associated with backyard flocks—the highest number ever recorded by CDC in a single year. And the Antibiotic Resistance Lab Network performed more than 12,000 tests to contain the spread of resistant infections, just to name a few accomplishments.

Tracking new and evolving threatsCDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) focuses on emerging diseases and diseases spread between animals and people. Our experts work around the clock to identify, track, control and prevent some of the deadliest diseases on the planet. This work includes tracking diseases across the globe and at home, developing innovations, investigating disease outbreaks in extreme conditions, and helping experts prepare for infectious disease threats.

Every day we are learning more about antibiotic resistance, which continues to be among the biggest health concerns in our country. In 2017, CDC took several important steps to combat antibiotic resistance, including rolling out a containment strategy to slow the spread of drug-resistant diseases in healthcare facilities—starting with a single case—and supporting 25 innovators through a CDC pilot project to develop solutions to antibiotic resistance crises.

Understanding the impact

We are also learning more about Zika virus. Zika was often in the headlines in 2016 and 2017, and the mosquito-borne virus continues to be a threat, especially for pregnant women and their fetuses. Last year, CDC experts shed light on a lesser-known effect of Zika virus infection: a link with Guillain-Barré syndrome (GBS), an uncommon illness of the nervous system. In 2017, CDC and partners conducted the first case-control study in the Americas that showed evidence linking Zika virus infection and GBS. This was just one of many vector-borne diseases CDC tackled in 2017.

Responding to new outbreaks

As we continued to work on lingering threats like antibiotic resistance and Zika, CDC also responded to new outbreaks in 2017, both at home and abroad. In the United States, we saw a range of illnesses connected to food products—from Salmonella infections linked to papayas to an Escherichia coli outbreak from soy nut butter. For the first time, scientists linked an outbreak of Seoul virus infections to pet rats in the United States, and AMD lab techniques proved critical in tracing this and other outbreaks. CDC scientists traveled across the globe in 2017 to investigate a myriad of outbreaks, including an outbreak of anthrax infections in animals in Namibia that posed a threat to human health. Experts helped respond to yellow fever outbreaks in countries including Brazil, and we continue that work today as the yellow fever outbreak in Brazil has expanded over the past two years and could affect US travelers.

Like CDC’s response to yellow fever outbreaks, much of last year’s work continues in 2018. We are closely tracking emerging infections like C. auris, continuing to study the effects of unusual diseases like Zika, and investigating and containing outbreaks of infections caused by a wide range of microbes such as Salmonella bacteria, monkeypox virus, and hemorrhagic fever viruses.

Want to learn more? Read the full NCEZID 2017 Accomplishments report, and follow NCEZID on Twitter @CDC_NCEZID.

Antimicrobial resistance: What is it? Why is it a problem? What is being done to stop it?

Antimicrobial resistance: What is it? Why is it a problem? What is being done to stop it? | www.APHLblog.org

By Kelly Wroblewski, director, infectious diseases, APHL

Antimicrobial resistance is arguably the most significant public health threat facing the world today. As resistance builds, the threat of severe illness or death from common infections becomes an increasing possibility for everyone.

What is antimicrobial resistance?

Antimicrobial resistance occurs when microbes, including bacteria, viruses, fungi and parasites, evolve or adapt to survive exposure to drugs or other treatments designed to kill them. Once the microbes have developed resistance, treatments used against them are rendered useless.

While all types of antimicrobial resistance are extremely concerning, antibiotic resistance – when bacteria become resistant to antibiotics – is often seen as posing the most serious health threat. Why is this?

Compared to other microbes, more bacteria are becoming increasingly resistant to treatment, and resistant bacteria can cause more adverse health outcomes in infected people. Antibiotics are also more commonly used than antiviral, antifungal or antiparasitic drugs.

How did antibiotic resistance become such a big problem?

While many complex issues have led to this urgent situation, three factors stand out:

1. The overuse and misuse of antibiotics in healthcare, agriculture and other aspects of day-to-day life is a significant contributor to antibiotic resistance. Simply stated, every time we use antibiotics inappropriately, we’re helping bacteria figure out how to outsmart and outperform them – to resist Inappropriate use includes taking antibiotics to treat viral infections, starting a course of antibiotics and not completing it, using antibiotics in agriculture to improve livestock survival and crop yields, and the liberal use of over-the-counter antibacterial soaps and ointments.

2. Development of new antibiotics and diagnostic tools to detect resistance has suffered due to a lack of investment. As bacteria develop resistance to existing drugs, scientists must work to develop new antibiotics to treat infections. However, for the past 30 years, antibiotic drug development has been stagnant and the prospects are not promising.

Prior to the drug development phase (bringing drugs to market) is drug discovery, the process of identifying candidate medications and active ingredients. This is a challenging and therefore incredibly expensive endeavor with few economic incentives. For companies that make it to the drug development phase, creating drugs that kill bad bacteria without killing good cells (including the host) is extremely difficult.

3. It is difficult to systemically detect, track and respond to new resistant pathogens and outbreaks without a comprehensive global surveillance system. To slow the spread of resistance, we have to know where to find it and have a plan to stop its spread. Though the United States has acted to counter resistant forms of diseases like TB and gonorrhea, it hasn’t taken a public health approach to diseases commonly found in health care settings like the superbug CRE. Failure to detect and stop the spread of these infections at the community level contributes to increased numbers of resistant infections, poor patient outcomes and increased healthcare costs. What’s more, aggressive detection and response efforts are needed to prevent local outbreaks from becoming pandemics.

What’s being done to slow or stop antimicrobial resistance?

The past few years have brought much needed progress. Finally, the US public health and health care systems have a comprehensive plan to combat this problem and resources to make it happen.

In 2014, the White House released the National Strategy on Combating Antibiotic-Resistant Bacteria and President Obama signed an Executive Order directing key federal agencies to take action to combat the rise of antibiotic resistant bacteria. In December 2015, Congress passed a budget providing $375 million to implement this strategy with $161 million going to CDC.

Since then, significant steps have been taken to move the dial in the right direction.

  • CDC has distributed approximately $67 million to local and state governments to improve their ability to detect and respond to existing and emerging resistance as well as implement strategies to improve antibiotic stewardship.
  • CDC has established the Antimicrobial Resistance Laboratory Network (ARLN) which will provide infrastructure and capacity for seven regional public health laboratories across the country to better identify and characterize some of the most significant antimicrobial resistance threats. In addition, the ARLN will provide resources to all state and several large local public health jurisdictions to improve their CRE surveillance capacity.
  • CDC, FDA and NIH have launched a comprehensive campaign aimed at improving antimicrobial stewardship in healthcare and reducing the frequency of antibiotic use in agriculture.
  • NIH and the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) launched the Antimicrobial Resistance Diagnostic Challenge, a $20 million prize competition that to stimulate innovation in the development of new, faster diagnostic tools.
  • CDC and FDA have collaborated to establish the Antimicrobial Resistance Isolate Bank, a repository of resistant pathogens that will be made available to companies developing new antibiotics and diagnostics.

These are significant and valuable steps forward. As these and future efforts get underway, collaboration across sectors will be critical to success. APHL is committed to supporting members and working closely with partners in the battle against antimicrobial resistance.

Read more:

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Fighting antimicrobial resistance requires clinical and public health response

Fighting antimicrobial resistance requires clinical and public health response | www.APHLblog.org

By Kelly Wroblewski, director, Infectious Disease Programs, APHL

They may be invisible to the naked eye and their names may be hard to pronounce, but antimicrobial resistant bacteria – bacteria that don’t respond to common antibiotics – pose a serious threat to the public’s health that is impossible to ignore. Until recently, antimicrobial resistance was seen as a problem to be addressed at the patient or healthcare facility level where the impact on the lives of people was immediately visible. Testing, responding to and controlling antimicrobial resistant pathogens was not often seen as something that fell under the purview of public health. But that’s finally changing.

I began my career as a clinical microbiologist. My first job was the lead micro technologist in a small hospital laboratory in a rural area at a time when hospital acquired MRSA – or “nosocomial MRSA” –rates had doubled. I still think about a specific case, an eight-month old baby girl who was a patient in the ER. I drew her blood myself, brought it to the lab and immediately inoculated it into blood culture bottles. A few days later, I was the person to isolate and identify MRSA in her sample. Several weeks after she had been transferred to a hospital with more advanced pediatric care, I saw her obituary in the paper.

MRSA control was a significant focus for the hospital where I worked. Because we were a small hospital, it was easy to keep track of patients who presented with MRSA, something I began doing shortly after starting my job. The patient population was mostly elderly and we often admitted, discharged and readmitted patients from the community’s three long-term care facilities and one rehabilitation center. It quickly became clear that the frequent transfer of patients between facilities was contributing to MRSA rates in the entire county. (Patient transfers between health care facilities is a well-known source of antimicrobial resistance spread.)

The hospital was able to work with the other facilities to implement infection control strategies to control (but not eliminate) the problem. This was possible because our small community allowed for open communication between healthcare facilities and meant that all testing was occurring in a single microbiology laboratory. Coordination of this sort of response and control effort would be much more difficult in a more populous area without external monitoring and assistance. This is where public health can and should play a vital role.

Fighting antimicrobial resistance requires clinical and public health response | www.APHLblog.orgWhen I transitioned into a career in public health and joined the staff at APHL, I was surprised to learn that public health laboratories play a very limited role in antimicrobial susceptibility testing for what (to me) was and is clearly a public health problem. That is finally going to change.

In the coming year, public health laboratories will play a critical role in the Obama administration’s National Action Plan to Combat Antimicrobial Resistance. One of the initial roles for public health labs was announced by CDC last week: the launch of the Antimicrobial Resistance Laboratory Network (ARLN). Seven public health laboratories have been chosen to provide testing in support of a national surveillance system that will monitor and respond to drug resistance throughout the country. This fall the chosen laboratories will receive training and begin implementing highly specialized tests that will allow them to respond to outbreaks, characterize and track different mechanisms of resistance, and to detect new kinds of resistance in the pathogens that most concern public health officials. All 50 state labs, DC and several large local labs will also be implementing testing to confirm and characterize carbapenem-resistant Enterobacteriaceae (CRE), which has been described as one of the most urgent threats to public health.

APHL looks forward to assisting CDC in the roll-out, training and coordination of this laboratory network in the coming months. My colleagues and I are eager to see the impact of the ARLN on antimicrobial resistance surveillance and response activities

While no one will ever know if the ARLN or other new public health measures would have prevented that baby girl from contracting and succumbing to MRSA, I am optimistic that the network represents a significant step forward.

Read more on antibiotic resistance:

Top photo: This 2014 image depicts a Centers for Disease Control (CDC) microbiologist holding up two Petri dish culture plates growing bacteria in the presence of discs containing various antibiotics. The isolate on the left plate is susceptible to the antibiotics on the discs and is therefore unable to grow adjacent to the discs. The plate on the right was inoculated with a carbapenem-resistant Enterobacteriaceae (CRE) bacterium that proved to be resistant to all of the antibiotics tested and is therefore able to grow near the discs.

The Best Insect Repellents Against Zika-virus Carrying Mosquitos

Repellent-150x150Source: The Best Insect Repellents Against Zika-virus Carrying Mosquitos With the Zika fever outbreak spreading across Latin America, many travelers and people in endemic areas are left wondering how best to protect themselves from mosquitoes.

Questioning seasonal variation in antibiotic prescribing

In the Northern hemisphere, cold and flu season usually strikes in late fall and early winter. Both are really unpleasant, but can’t be treated by antibiotics because viruses cause the common cold and influenza. Antibiotics

Get Smart: 4 easy ways you can combat antibiotic resistance

By Kelly Wroblewski, director, infectious disease, APHL

It has been nearly 90 years since Alexander Fleming took the first step toward discovering penicillin in 1928. Since mass production began in 1941, people have been using antibiotics to treat minor and major infections alike. One of the earliest uses of antibiotics was in the treatment of infected wounds suffered by Allied troops in World War II, and this undoubtedly saved lives. Today antibiotics are used to treat everything from minor scrapes to urinary tract infections to bacterial meningitis.  People under the age of 75 don’t remember the world without them; a world where any infection, small or large, could lead to serious illness or death.

Get Smart: 4 easy ways you can combat antibiotic resistance | www.APHLblog.orgAntibiotics are a valuable shared resource for all human beings, one that we certainly take for granted. In the last two decades, the world has seen a dramatic increase in antibiotic resistance (when bacteria stop responding to drugs designed to kill them), reducing the number of antibiotics that can effectively treat bacterial infections. Over prescription and misuse of antibiotics is a key contributing factor in the spread of resistance. If we do not take swift and significant action to address our rampant antibiotic use, we run the risk of returning to a world where people die from what we now perceive as minor illnesses or infections.

According to CDC, right now antibiotic resistant infections are responsible for at least 2 million illnesses and 23,000 deaths in the US every year, and this number is only expected to grow. Increased resistance to commonly used antibiotics leads to fewer treatment options for the most vulnerable individuals including premature infants, cancer patients and the elderly. Some resistant bacteria also have the potential to spread to others, making antibiotic resistance one of the most significant and challenging public health threats we currently face.

This is a public health problem that cannot be combated by doctors and scientists alone. Reversing this trend will take a concerted effort from the entire population to become better antibiotic stewards.

What can you do to help combat antibiotic resistance?

Get Smart: 4 easy ways you can combat antibiotic resistance | www.APHLblog.org1. Ask the Right Questions. When your healthcare provider suggests treatment that includes antibiotics, don’t be afraid to ask if it is truly the best way to treat your infection. It could be just as effective to treat your symptoms and let the illness run its course. Don’t make this decision alone, though. Talk with your healthcare provider.

2. Know what types of illnesses are most likely to respond to antibiotic treatment. Antibiotics will do nothing to fight off viruses like the common cold and flu. This table provides a good quick reference to when antibiotics might be needed.

3. Ask for the test. Ask your healthcare provider to order tests that will identify the source of your illness. If necessary, you can also request an antibiotic susceptibility test to ensure that the antibiotic being prescribed is the correct one. (Not all antibiotics work to fight all infections.) This eliminates unnecessary use of incorrect antibiotics which can lead to unnecessary treatment and increased risk of resistant infections in the future.

4. If you do need antibiotics, follow the instructions and take the full course. Failure to follow the instructions of the prescription (how much to take and how often to take it) can lead to the development of antibiotic-resistance among the harmful bacteria you are trying to treat. Harmful bacteria that are exposed to antibiotics may begin to develop properties that allow them to survive – or become resistant to – exposure to antibiotics. Although it may be tempting to stop taking an antibiotic when you start to feel better, the full treatment is necessary to completely eliminate the cause of your illness. Stopping treatment early can result in the illness reoccurring later and help the proliferation and spread of antibiotic resistant bacteria.

Read more about APHL’s five year commitment to slow the emergence of antibiotic-resistant bacteria, detect resistant strains, preserve the efficacy of our existing antibiotics and prevent the spread of resistant infections. Representing Public Health Labs at the White House Forum on Antibiotic Stewardship

Get Smart: 4 easy ways you can combat antibiotic resistance | www.APHLblog.org