How to Halt the Spread of Drug-resistant Bacteria
An infectious disease clinician and researcher relies on high-level teamwork in waging a methodical war on the global antimicrobial threat.
Army Colonel Paige E. Waterman, MD ’03, FACP, FIDSA, is a leader in the battle against escalating antimicrobial resistance (AMR), which limits treatment options for 2 million people per year in the United States, 23,000 of whom die from resistant infections, according to the Centers for Disease Control. While the global threat is difficult to assess, the Organisation for Economic Co-operation and Development warns that 2.4 million people in North America, Australia and Europe alone could die from superbug infections by 2050 if more isn’t done to stem AMR.
It doesn’t take much for these resistance genes to be shared amongst bacteria. They tend to travel in packs.
Dr. Waterman has worked for the past nine years for the Department of Defense (DOD) in highly collaborative national and international teams to curb rising drug resistance through the surveillance and early detection of emerging pathogens, policy creation and coordinated antimicrobial stewardship. In 2015, after the Obama administration announced the National Action Plan for Combating Antibiotic-Resistant Bacteria, she was identified as the DOD lead for the Interagency Task Force and newly created Presidential Advisory Council for Combating Antibiotic-Resistant Bacteria (CARB), which includes experts from the CDC, National Institutes of Health (NIH), Food and Drug Administration, Agency for Healthcare Research and Quality, and the Department of Agriculture and Department of Veterans Affairs, among other federal agencies. Numerous other DOD committee appointments soon followed, including co-chair for the CARB Antimicrobial Stewardship Policy Working Group, DOD lead for the Transatlantic Task Force on AMR and reporting lead for the Global Health Security Agenda’s antimicrobial resistance action plan.
“Early on, when I was participating in policy development on behalf of the DOD, I would find myself in meetings filled with luminaries in the field and wonder, ‘Why am I here? What do I bring to the table?’” Dr. Waterman said. “What I believe I bring to the table is the fact that I am a physician. I understand what it means to work with patients. I understand what we’re looking for from the bench to be able to translate for use in patients. I understand the science and can help translate it for my clinical counterparts into a policy or direction that makes sense from a broader perspective.”
She served for four years as deputy director of the nascent Multidrug-Resistant Organism Repository and Surveillance Network (MRSN), established at the Walter Reed Army Institute of Research (WRAIR) in 2009 to collect pathogens for epidemiologic and molecular characterization, profiling and centralized archiving. Today, the laboratory operates in support of all U.S. Armed Forces health facilities and serves as a national and global resource in identifying the source of new AMR infections that, Dr. Waterman observes, are “becoming a fact of life” given the long list of challenges, including international travel, the import and export of goods, varying innate resistance profiles among human beings and within our food supply, and different levels of infection control at healthcare settings both at home and abroad.
MRSN maintains a collection of more than 65,000 clinical bacteria isolates for reference.
“The lab collects every isolate and looks at every isolate,” Dr. Waterman said. “We can get down to the single nucleotide level to see what changed genetically, which can provide information on how the pathogen or resistance gene is being transmitted and the pattern. We have to find patient 0, not to place blame, but to figure out the point of initial infection and mechanism of spread in order to identify places to halt the spread.”
In 2016, researchers at MRSN identified the first person in the United States to be infected with bacteria resistant to the antibiotic colistin, a last-resort therapy for many drug-resistant pathogens. Investigators were already on high alert after the colistin-resistant gene mcr-1 was first discovered in China in 2015.
“When that sequence was published, everyone set out to screen their repositories for any evidence of the gene,” Dr. Waterman said. “As the result of our CARB work — including our strong collaboration with our colleagues at the CDC, NIH and USDA, and our communications network — we were all quickly informed when the MRSN discovered it in an E. coli isolate and that the USDA had also isolated a case in an animal. That discovery culminated in a joint press release. It was a good news story, not because we found resistance — that was inevitable — but because we identified it relatively quickly and we got the information out equally as efficiently.
Nobody sat on the information for months trying to figure out all the details of transmission or finalize a manuscript for publication. It was a good demonstration in how far we’ve come in communicating and information sharing between agencies and with the public.”
The patient, a 49-year-old female U.S. military beneficiary, survived because the bacteria she harbored was not resistant to carbapenems, a class of broad spectrum antibiotics that while potent, poses a risk of healthcare-associated infections if overused.
“In her case, it wasn’t a horror story — but it is not a big jump to becoming one,” Dr. Waterman said. “It doesn’t take much for these resistance genes to be shared amongst bacteria. They tend to travel in packs. If you have one, you usually have many. But you can’t always assume that you have all of them.”
Dr. Waterman, now the assistant director for biological threat defense in the Office of Science and Technology Policy, Executive Office of the President, recalls an AMR baptism by fire during a three-year National Capital Consortium fellowship in infectious diseases at the Walter Reed National Military Medical Center.
Working on an interagency level across the government is great because we all have the same end goal in mind
“We were seeing a lot of injured soldiers coming back from military operations in the Middle East with a lot of resistant bacteria, including Acinetobacter baumannii, which has been around a long time but was having a resurgence,” she said. “Probably the second day of my fellowship in 2007, I was in the OR with surgeons and I noticed they were putting cement beads together and preparing to put them inside the patient. They were impregnating the beads with antibiotics. There’s some literature to suggest a benefit to delivering antibiotics at the source of a deep wound infection in addition to giving systemic therapy. I asked what antibiotic they were using and was told colistin. When I asked what dose, they said, ‘That’s why you’re here.’ That was my second day as an ID fellow. I did not have an answer to their question.”
Dr. Waterman scoured the literature and, finding nothing on the use of colistin in question, conducted her own research — “what I would call now a rudimentary project,” she said — making various antibiotic-containing beads and testing surrounding effluents for any residual bacteria. She went on to publish a paper on the subject, one of more than 40 manuscripts to her credit, most of them on AMR.
A nurse and nurse practitioner before she trained as a physician and scientist, Dr. Waterman is a consummate team player.
“Working on an interagency level across the government is great because we all have the same end goal in mind,” she said. “No one wants antibiotic resistance or the complications it causes. We all want improved prevention, faster diagnostic tests and better treatments for infections. But we all approach the problem from our own departmental, agency or educational perspectives. In the beginning, I noticed physicians asking one type of question and PhD scientists asking another type of question. So I had to merge the two, saying these questions are good, but this is how we need to focus our approach to create the best benefit for the people.
“We are all in this together,” Dr. Waterman said. “It takes a pooling of resources and minds to come up with options for the future. We like to say it takes the whole of government, but to be honest, AMR is beyond government. It’s public/private partnerships that offer the way forward, the expertise and resources, to combat this pervasive chink in our population’s armor.”
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