[Senate Hearing 118-203]
[From the U.S. Government Publishing Office]
S. Hrg. 118-203
SUPERBUGS: THE IMPACT OF
ANTIMICROBIAL RESISTANCE
ON MODERN MEDICINE
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON PRIMARY HEALTH AND RETIREMENT SECURITY
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED EIGHTEENTH CONGRESS
FIRST SESSION
ON
EXAMINING THE SUPERBUGS, FOCUSING ON THE IMPACT OF ANTIMICROBIAL
RESISTANCE ON MODERN MEDICINE
__________
JULY 11, 2023
__________
Printed for the use of the Committee on Health, Education, Labor, and
Pensions
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://www.govinfo.gov
__________
U.S. GOVERNMENT PUBLISHING OFFICE
54-493 PDF WASHINGTON : 2024
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
BERNIE SANDERS (I), Vermont, Chairman
PATTY MURRAY, Washington BILL CASSIDY, M.D., Louisiana,
ROBERT P. CASEY, JR., Pennsylvania Ranking Member
TAMMY BALDWIN, Wisconsin RAND PAUL, Kentucky
CHRISTOPHER S. MURPHY, Connecticut SUSAN M. COLLINS, Maine
TIM KAINE, Virginia LISA MURKOWSKI, Alaska
MAGGIE HASSAN, New Hampshire MIKE BRAUN, Indiana
TINA SMITH, Minnesota ROGER MARSHALL, M.D., Kansas
BEN RAY LUJAN, New Mexico MITT ROMNEY, Utah
JOHN HICKENLOOPER, Colorado TOMMY TUBERVILLE, Alabama
ED MARKEY, Massachusetts MARKWAYNE MULLIN, Oklahoma
TED BUDD, North Carolina
Warren Gunnels, Majority Staff Director
Bill Dauster, Majority Deputy Staff Director
Amanda Lincoln, Minority Staff Director
Danielle Janowski, Minority Deputy Staff Director
SUBCOMMITTEE ON PRIMARY HEALTH AND RETIREMENT SECURITY
ED MARKEY, Massachusetts, Chairman
PATTY MURRAY, Washington ROGER MARSHALL, M.D., Kansas,
TAMMY BALDWIN, Wisconsin Ranking Member
CHRISTOPHER S. MURPHY, Connecticut RAND PAUL, M.D., Kentucky
MAGGIE HASSAN, New Hampshire SUSAN M. COLLINS, Maine,
TINA SMITH, Minnesota LISA MURKOWSKI, Alaska
BEN RAY LUJAN, New Mexico MIKE BRAUN, Indiana
JOHN HICKENLOOPER, Colorado MARKWAYNE MULLIN, Oklahoma
BERNIE SANDERS (I), Vermont, (ex TED BUDD, North Carolina
officio) BILL CASSIDY, M.D., Louisiana, (ex
officio)
C O N T E N T S
----------
STATEMENTS
TUESDAY, JULY 11, 2023
Page
Subcommittee Members
Markey, Hon. Ed, Chairman, Subcommittee on Primary Health and
Retirement Security, Opening statement......................... 1
Marshall, Hon. Roger, Ranking Member, a U.S. Senator from the
State of Kansas, Opening statement............................. 2
Witnesses
Apley, Michael, Professor, College of Veterinary Medicine at
Kansas State University, Manhattan, KS......................... 5
Prepared statement........................................... 6
Boucher, Helen, Dean and Professor of Medicine, Tufts University
School of Medicine, Boston, MA................................. 9
Prepared statement........................................... 11
Lawrence, Melanie, Healthcare Advocate, Fairhaven, MA............ 19
Prepared statement........................................... 21
Miller, Christine Ann, President and Chief Executive Officer,
Melinta Therapeutics, New York, NY............................. 24
Prepared statement........................................... 26
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.
Markey, Hon. Ed:
Letter from the Healthcare Leadership Council................ 50
SUPERBUGS: THE IMPACT OF
ANTIMICROBIAL RESISTANCE
ON MODERN MEDICINE
Tuesday, July 11, 2023
U.S. Senate,
Subcommittee on Primary Health and Retirement Security,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The Subcommittee met, pursuant to notice, at 10:02 a.m., in
room 430, Dirksen Senate Office Building, Hon. Ed Markey,
Chairman of the Subcommittee, presiding.
Present: Senators Markey [presiding], Murphy, Hassan,
Smith, Hickenlooper, Marshall, Braun, and Budd.
OPENING STATEMENT OF SENATOR MARKEY
Senator Markey. Good morning. The Senate, Health,
Education, Labor, and Pensions Subcommittee on Primary Health
and Retirement Security, will come to order. Thank you for
joining us today for the Primary Health and Retirement
Subcommittee hearing, Superbugs: The Impact of Antimicrobial
Resistance on Modern Medicine.
Thank you especially to Ranking Member Marshall, to you and
your staff's shared commitment to preparing for and preventing
the antimicrobial resistance crisis in the United States. This
is the type of partnership that drives results ultimately in
Congress. More than 100 years ago, the discovery of antibiotics
revolutionized modern medicine.
Some experts consider penicillin to be the single most
important drug ever created. Antibiotics alone have extended
our average lifespan by 23 years. But the rise in antimicrobial
resistance threatens to undo 100 years of medical progress.
Minor infections could become incurable, leaving patients
with chronic illnesses like cystic fibrosis most at risk.
Routine surgeries could turn into deadly procedures. A paper
cut could become lethal. But with the benefit of a century of
scientific advancement on our side, this does not have to be
our fate.
Our scientists and medical leaders already know what needs
to be done. They know that the only medicine better than an
antibiotic is prevention. They know that we must use
antibiotics responsibly. They know that keeping people healthy
and out of the hospital is critical to reducing anti-microbial
resistance. Yet more than 100 million Americans lack access to
primary care. But we here in Congress can do something about
that.
We can invest in our community health centers and public
health infrastructure. We can build a world class health system
that reaches every person in every community, from Kansas to
Massachusetts, and invest in our workforce, empowering a legion
of medical professionals to prevent infections from turning
into pandemics. And we can keep our people healthy by keeping
our planet healthy.
Last week, we saw the four hottest days on planet Earth
ever recorded. While the planet will turn our coastlines and
waterways into petri dishes, diseases will spread faster and
new strains will spread farther. Our climate crisis feeds the
antimicrobial resistance crisis, and the only answer is to act
now.
We need a whole of Government approach to prevent the next
public health emergency. And as we saw with COVID-19 pandemic,
when crisis strikes, it doesn't strike in a vacuum. An
antimicrobial resistance crisis will disproportionately
threaten the people who interact the most with the medical
system.
It will threaten our health care workers, our friends and
family who have disabilities, who are pregnant or who are
elderly. It will worsen an opioid epidemic and strike in every
community whether or not they have the resources to respond. It
will bankrupt our working class and strain a system already
plagued by inequality.
But with this wisdom of hindsight, we can improve our
pandemic preparedness. We can build a resilient health care
system designed with people at the very center--designed to
take care of all Americans. We can deliver the ingenuity of
American innovation, but it will only save us from crisis if
the treatment is accessible for everyone. Just as a vision
without funding is a hallucination, innovation without access
is a fantasy.
We can and must create a different future, one that does
not repeat the sins of the past. The witnesses here today,
doctors on the front lines, patients living with the risk of
antimicrobial resistance, companies developing new medications,
and researchers connecting the health of our people and our
environment will light our path forward. They are fighting for
a better future and Congress must listen and respond. It is
time that we guarantee are prepared an equitable whole of
Government plan to prevent a crisis.
With that, I will now turn to Ranking Member, Senator
Marshall, for his opening statement.
OPENING STATEMENT OF SENATOR MARSHALL
Senator Marshall. Well, thank you, Mr. Chairman, for
agreeing to hold this hearing on anti-microbial resistance. I
got to tell you, I could barely sleep last night. I was so
excited to get here. This is why we came to Congress, was to
fix problems like this. And I will tell you why this is near
and dear to my heart.
Certainly, since a second year medical student, tried to
understand bacteria and yeast infections and fungus, but the
story that I remember is showing up for my OB-GYN residency
program. We were delivering 15 to 20 babies a day, working 36
hour shifts. But the story that haunted everybody was a young
lady that had a C-section and had died maybe 3 months before I
got there.
She died from a resistant bacteria, from sepsis, a
complication from a C-section. And very few days or weeks went
by where we didn't talk, or they didn't talk about that case.
Was there a month or two and we were having a very high
infection rate, higher than I was comfortable with for post-
operative patients.
I started culturing patients, and that is something you
typically don't do when you have a multi-bacteria gram
positive, gram negatives, and anaerobes causing these types of
infections. But I cultured several people, and they had a
methicillin resistant staph aureus. I had never even seen a
patient with it, but I had read about it, and then I started to
go, why are all these patients having a methicillin resistant
staph aureus?
I looked into it further and they were using Primaxin,
called Gorillacillin, as a prophylactic and were treating
common urinary tract infections--they were treating everything
with it. And obviously this new, I suppose it was a third or
fourth generation cephalosporin, was inducing drug resistance.
So here we are today. And why is this important?
3 million Americans this year will get some type of an
antimicrobial resistance superbug this year. 100 Americans will
die today. 100 will die tomorrow and every day this year from
some type of a resistant bug. And I see the need for this
rising as diabetes and obesity overwhelm our society.
Those are setups for more resistant organisms. And again,
in my field of obstetrics, our C-section rates are going up for
the same reasons, and we are going to have more infections and
more resistant bugs, and then, of course, sexually transmitted
diseases. For years, we have had penicillin resistant
gonorrhea, but now it is resistant to Rocephin. Zithromax is
not working as well.
It is certainly something I saw every day in my practice.
It is interesting, as I did some research on this, the CDC and
the World Health Organization both agree that human overuse is
the main cause of this increased antimicrobial infections, and
I am sure Dr. Apley will talk about this.
But one of the first things I did when I was running for
office, I visited most every dairy, most every feedlot in the
state, and I was so impressed that there was a veterinarian, if
not on staff, literally consulting on a weekly basis, focused
on nutrition and cutting back the antibiotic use. And I am so
impressed with how fewer antibiotics those industries are using
today compared to 2017 when we passed legislation. I bet Dr.
Apley will talk a little bit about that as well.
I am proud what we have done in agriculture, but we need to
look in the mirror. We, meaning physicians, nurse
practitioners, and PAs need to look in the mirror. Half of the
antibiotics that we prescribe are probably not indicated. Now,
I wish I could tell you which half it is, but certainly my
profession needs to look in the mirror.
We--need to do more cultures and pay more attention to this
as well. Here is the challenge before us. I talked about those
100 people dying every day from some type of resistant
organism. That is probably caused by 20 or 30 different
bacteria. It is not that you are going to develop one
antibiotic that is going to take care of all of these.
You develop an antibiotic, and maybe it is specific to an
infection from a kidney infection, and another antibiotic could
be specific for pneumonia, and another antibiotic for a pelvic
infection. So that is why it is so costly.
That is why it is so costly to develop these, realizing
that we need 20 or 30 new antibiotics to take on these key
infections, as opposed to say a diabetic drug that's going to
be able to you get that to tens of millions of patients or even
Alzheimer's drug. If it is developed, it will probably be given
to a million patients. When we develop these types of
antibiotics, we are hopefully only going to use them each a
handful of times.
It just makes the economics of it next to impossible. We
have many professional friends and colleagues have asked me to
have this patient centered hearing, so I am so proud of the
all-star group of witnesses we have. I know it is going to be a
great hearing.
Again, I want to emphasize, thank you to your staff as
well, Chairman, and the Committee staff working together to
bring this to light. This is an issue that this Committee can
literally make a difference today.
People ask me why I left the practice of medicine to come
here, and I would tell them, look, in medicine I could impact
30, 40, 50 people a day. Here, you and I can impact the lives
of thousands of people, certainly 100 people a day that I
mentioned dying from an antimicrobial resistant bacteria.
Proud to be here and look forward to hearing from our
witnesses. Thank you.
Senator Markey. I would ask Senator Marshall for you to
introduce our first witness, if you would.
Senator Marshall. [Technical problems]--his last 6 years in
Congress. Dr. Apley, of course, is a veterinarian with a Ph.D.
in pharmacology at the College of Veterinary Medicine at the
Kansas State University, home of the fighting Wildcats.
He teaches multiple courses related to food, animal
medicine, clinical pharmacology, antimicrobial resistance. His
research interests include infectious disease, antibiotic
efficacy, resistance, antibiotic stewardship, which is
certainly an issue here today, drug residues, that will be
interesting in the applications of drugs in food animals.
Dr. Apley is nationally recognized for his work and is
among the most influential veterinarians in cattle industry. He
recognizes the value of his work. Dr. Apley was appointed a
voting member of the Presidential Advisory Council on combating
antibiotic resistant bacteria. He recently completed two terms
on the council serving as vice chair.
He currently serves as a diplomat of the American College
of Veterinary and Clinical Pharmacology and is a member of the
American Veterinary Medical Association. Dr. Apley, thank you
so much for agreeing to be here and to testify. We look forward
to your information. Should I introduce the next one or--Dr.
Apley, go ahead.
Senator Markey. Dr. Apley, whenever you feel comfortable,
please begin.
STATEMENT OF MICHAEL APLEY, PROFESSOR, COLLEGE OF VETERINARY
MEDICINE AT KANSAS STATE UNIVERSITY, MANHATTAN, KS
Dr. Apley. Thank you. Chairman Markey, Ranking Member
Marshall, Members of the Subcommittee, and my esteemed
colleagues, good morning. My name is Mike Apley. I am a
veterinarian and clinical pharmacologist at Kent State
University College of Veterinary Medicine.
I also serve as an alternate member on the American
Veterinary Medical Association Committee on Antimicrobials.
Clinical use of antibiotics and research into their optimal use
has been my focus since 1987. Today, we are addressing the
issue of antibiotic resistance, more specifically the issue of
acquired antibiotic resistance, where antibiotics that were
previously effective against the bacterial pathogen have lost
the ability to have an impact on the outcome of disease caused
by that pathogen in humans or animals.
We can think of worse--resistance as the worst case
scenario of there being no possible treatment for a bacterial
disease, or resistance can mean that our initial antibiotic
choice doesn't work, and it is later in the disease process
when an effective antibiotic is used. This delayed, effective
intervention can result in a more prolonged disease course and
increase chance of debilitation or an eventual failure of
antibiotic therapy. Resistance to our initial antibiotic choice
can also mean that the remaining options have undesirable side
effects which complicate recovery.
Acquired antibiotic resistance may occur due to a mutation
in bacterial DNA, which is passed down through the subsequent
generation, but the other more alarming route for acquiring
resistance occurs through the horizontal transfer of resistance
genes between different bacteria by means of transferable
genetic elements, which encode for a resistance mechanism, a
method of transfer, and a means to be incorporated into the DNA
of the bacteria receiving the genetic elements.
These transferable genetic elements may contain the genetic
codes of more than one resistance mechanism, with many of these
mechanisms encoding resistance to multiple antibiotics. This is
termed multiple drug resistance, or MDR. The conditions leading
to acquired antibiotic resistance reaching a point where this
resistance has an impact on the use of an antibiotic include
frequently applied antibiotic selection pressure, a highly
mutable population of bacteria with a short generation time.
This selection pressure may result in a higher proportion
of the pathogen population being resistant, as well as the
expansion of an already resistant bacterial population, by
reducing the numbers of other bacteria competing for the same
resources. The latter situation highlights the importance of
the health impact of our normal bacterial flora. To be clear,
this is a generalized account of the nature of acquired
antibiotic resistance.
Discussion should be held in relation to specific
combinations of antibiotic exposure, the bacteria of interest,
and the environment in which the antibiotic bacterial
interaction occurs. We have pathogens which have acquired
resistance to most and in some cases all of our antibiotic
options, and we have pathogens which maintain susceptibility to
our most basic first line antibiotic choices.
The severity of the antibiotic resistance challenge to our
health is illustrated in the characterization of the major
resistance threats to human health by the Centers for Disease
Control and Prevention, or the CDC.
More specifically, there are 2019 Antibiotic Resistant
Threats Report identifies 18 bacteria and fungi estimated to be
involved in more than 2.8 million antibiotic resistant
infections each year, resulting in 35,000 deaths. When severe
and potentially fatal diarrhea caused by clostridioides
difficile related antibiotic use is considered, this raises the
estimates to 3 million infections and 48,000 deaths.
The complex relationship of antibiotic resistance to our
health care system is reflected in a 2022 special report by the
CDC on the impact of COVID-19 on antibiotic resistance. The
American Veterinary Medical Association has also published a
document identifying antibiotic resistance challenges
encountered in veterinary species. Consideration of the
challenge of antibiotic resistance has led to the National
Action Plan for combating antibiotic resistant bacteria, or
CARB. An important component of CARB is the one health approach
which recognizes the relationships between the health of
humans, animals, plants, and the environment.
Consistent with this one health approach, the Food and Drug
Administration Center for Veterinary Medicine is in the last
year of the current 5 year action plan for supporting
antimicrobial stewardship in veterinary settings, with the
recent progress report. I would also like to highlight a
resource on antibiotic resistance within the U.S. Department of
Health and Human Services, the Presidential Advisory Council on
Combating Antibiotic Resistant Bacteria, or PACCARB.
The PACCARB produced the first of 11 reports from 2016,
with the most recent report in 2023. I suggest this resource is
not only a way to hear from experts, but also is a bridge to
many additional resources in the field. Thank you very much for
the opportunity to be here this morning, and I look forward to
our discussion.
[The prepared statement of Dr. Apley follows.]
prepared statement of michael apley
Chairman Markey, Ranking Member Marshall, Members of the
Subcommittee, colleagues, good morning. I am Mike Apley, a veterinarian
and clinical pharmacologist at the Kansas State University College of
Veterinary Medicine. I also serve as an alternate member on the
American Veterinary Medical Association Committee on Antimicrobials.
Clinical use of antibiotics and research into their optimal use has
been my professional focus since 1987.
Today we are addressing the issue of antibiotic resistance, more
specifically the issue of acquired antibiotic resistance where
antibiotics that were previously effective against a bacterial pathogen
have lost the ability to have an impact on the outcome of disease
caused by that pathogen in humans or animals. We can think of
resistance as the worst case scenario of there being no possible
treatment for a bacterial disease. Or, resistance can mean that our
initial antibiotic choice doesn't work, and it is later in the disease
process when an effective antibiotic is used. This delayed effective
intervention can result in a more prolonged disease course, an
increased chance of debilitation, or an eventual failure of antibiotic
therapy. Resistance to our initial antibiotic choice can also mean that
the remaining options have undesirable side effects which complicate
recovery.
How we Identify Resistance in the Laboratory
We identify and quantify resistance through antimicrobial
susceptibility testing. Currently, the most common method is to grow
the offending bacteria in the lab and expose it to multiple
concentrations for each of multiple antibiotics. Whether or not growth
of the bacteria occurs at different concentrations allows the
classification of the bacteria as ``susceptible'' or ``resistant'' to
each antibiotic based on established interpretive criteria. The methods
and application of antimicrobial susceptibility testing continue to
evolve. We are in a period of transition to more rapid tests, such as
detecting genes identifying both the bacterial pathogen and the
resistance genes present. The importance of continuing to advance rapid
tests which identify the disease, and the most appropriate therapeutic
approach cannot be overstated.
How Resistance Happens
Acquired antibiotic resistance may occur due to a mutation in
bacterial DNA which is passed down through subsequent generations. The
other more alarming route for acquiring resistance occurs through the
horizontal transfer of resistance genes between different bacteria by
means of transferrable genetic elements which encode for a resistance
mechanism, a method of transfer, and the means to be incorporated into
the DNA of the bacteria receiving the genetic elements. These
transferable genetic elements may contain the genetic codes for more
than one resistance mechanism, with many of these mechanisms encoding
resistance to multiple antibiotics. This is termed multiple drug
resistance (MDR).
The number and types of antibiotic resistance genes which have been
identified are extensive. Resistance mechanisms include altering
antibiotic binding sites, efflux pumps which pump the antibiotic back
out of the bacterial cell, altered physiological processes, and enzymes
which inactivate the antibiotic. As examples related to specific
antibiotic groups, approximately 2,800 unique proteins functioning as
b-lactamases have been identified. \1\ Depending on their specific
structure and activity, these enzymes are capable of inactivating
antibiotics such as the penicillins, cephalosporins, monobactams, and
carbapenems. There are 46 different genes identified which encode for
tetracycline resistance, and resistance to phenicols is due to genes
which are categorized into 37 different groups. \2\ An important
concept is that antibiotic use does not create these resistance
mechanisms but can select for them when they exist in a population of
bacteria exposed to an antibiotic. It is also important to recognize
that even appropriate antibiotic use targeting a specific pathogen may
select for a resistant subpopulation of that pathogen, and also for
resistant subpopulations in the surrounding ``bystander'' bacterial
populations.
---------------------------------------------------------------------------
\1\ Bush K. Past and Present Perspectives on b-lactamases.
Antimicrob Agents Chemother 2018;62(10):e01076-18.
\2\ Roberts MC and Schwarz S. Tetracycline and Phenicol Resistance
Genes and Mechanisms: Importance for Agriculture, the Environment, and
Humans. J Environ Qual 45:576-592, 2016.
The conditions leading to acquired antibiotic resistance reaching a
point where this resistance has an impact on the use of an antibiotic
include (1) frequently applied antibiotic selection pressure on (2) a
highly mutable population of bacteria with (3) a short generation time.
This selection pressure may result in a higher proportion of a pathogen
population being resistant as well as the expansion of an already
resistant bacterial population by reducing the numbers of other
bacteria competing for the same resources. The latter situation
highlights the importance of the health impact of our normal bacterial
---------------------------------------------------------------------------
flora.
To be clear, this is a generalized account of the nature of
acquired antibiotic resistance. Discussions should be held in relation
to specific combinations of antibiotic exposure, the bacteria of
interest, and the environment in which the antibiotic--bacterial
interaction occurs. We have pathogens which have acquired resistance to
most (in some cases all) of our antibiotic options, and we have
pathogens which maintain susceptibility to many of our most basic,
first-line antibiotic choices.
Antibiotic Resistance vs. Virulence
Antibiotic resistance is not necessarily combined with virulence,
which is the ability to cause disease. However, when we have the
combination of antibiotic resistance and virulence in a readily
communicable pathogen, we have the potential for a substantial
challenge across the one health spectrum.
What are the Challenges?
The severity of the antibiotic resistance challenge to our health
is illustrated in the characterization of the major resistance threats
to human health by the Centers for Disease Control and Prevention
(CDC). \3\ More specifically, their 2019 antibiotic resistance threats
report identifies 18 bacteria and fungi estimated to be involved in
more than 2.8 million antibiotic resistant infections each year,
resulting in 35,000 deaths. \4\ When severe and potentially fatal
diarrhea caused by Clostridiodes difficile related to antibiotic use is
considered, this raises the estimates to 3 million infections and
48,000 deaths. The complex relationship of antibiotic resistance to our
healthcare system is reflected in a 2022 special report by the CDC on
the impact of COVID-19 on antibiotic resistance. \5\ The American
Veterinary Medical Association (AVMA) has also published a document
identifying antibiotic resistance challenges encountered in veterinary
species. \6\ Antibiotic resistant pathogens in common between the CDC
report and at least one veterinary species in the AVMA report are
multidrug-resistant Pseudomonas aeruginosa, drug-resistant non-
typhoidal Salmonella, and methicillin-resistant Staphylococcus aureus.
---------------------------------------------------------------------------
\3\ Centers for Disease Control and Prevention. Antimicrobial
Resistance--National Infection & Death Estimates for Antimicrobial
Resistance. https://www.cdc.gov/drugresistance/national-estimates.html
Accessed 7-8-2023.
\4\ Centers for Disease Control and Prevention. Antibiotic
Resistance Threats in the United States, 2019. https://www.cdc.gov/
drugresistance/biggest-threats.html Accessed 7-8-2023.
\5\ Centers for Disease Control and Prevention. 2022 Special
Report: COVID-19 United States Impact on Antibiotic Resistance. https:/
/www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf Accessed
7-8-2023.
\6\ American Veterinary Medical Association. Antimicrobial-
Resistant Pathogens Affecting Animal Health. https://www.avma.org/
resources-tools/one-health/antimicrobial-use-and-antimicrobial-
resistance/antimicrobial-resistant-pathogens-affecting-animal-health
Accessed 7-8-2023.
---------------------------------------------------------------------------
What are Plans for Responding to the Threat of Antibiotic Resistance?
Consideration of the challenge of antibiotic resistance has led to
the National Action Plan for Combating Antibiotic-Resistant Bacteria,
2020-2025 (CARB). \7\ An important component of CARB is a one health
approach ``which recognizes the relationships between the health of
humans, animals, plants, and the environment''. CARB has 5 major goals.
---------------------------------------------------------------------------
\7\ U.S. Department of Health and Human Services. Office of the
Assistant Secretary for Planning and Evaluation. National Action Plan
for Combating Antibiotic-Resistant Bacteria, 2020-2025. https://
aspe.hhs.gov/reports/national-action-plan-combating-antibiotic-
resistant-bacteria-2020-2025 Accessed 7-8-2023.
Slow the emergence of resistant bacteria and prevent
---------------------------------------------------------------------------
the spread of resistant infections
Strengthen national One Health surveillance efforts
to combat resistance
Advance development and use of rapid and innovative
diagnostic tests for identification and characterization of
resistant bacteria
Accelerate basic and applied research and development
for new antibiotics, antifungals, other therapeutics, and
vaccines
Improve international collaboration and capacities
for antimicrobial-resistance prevention, surveillance, control,
and drug research and development
Consistent with this one health approach, the Food and Drug
Administration Center for Veterinary Medicine (FDA CVM) is in the last
year of the current 5-year action plan for supporting antimicrobial
stewardship in veterinary settings, with a recent progress update. \8\
The FDA CVM plan has 3 major goals.
---------------------------------------------------------------------------
\8\ U.S. Food and Drug Administration Center for Veterinary
Medicine. FDA Delivers Progress Update on 5-year Veterinary Stewardship
Plan https://www.fda.gov/animal-veterinary/cvm-updates/fda-delivers-
progress-update5-year-veterinary-stewardship-plan-publishes-report-
about-antimicrobial Accessed 7-8-2023.
Align antimicrobial drug product use with the
---------------------------------------------------------------------------
principles of antimicrobial stewardship
Foster antimicrobial stewardship in veterinary
settings
Enhance monitoring of antimicrobial resistance and
antimicrobial drug use in animals
I would like to highlight a resource on antibiotic resistance
within the U.S. Department of Health and Human Services, The
Presidential Advisory Council on Combating Antibiotic-Resistant
Bacteria (PACCARB). \9\ The PACCARB produced the first of 11 reports in
2016 with the most recent report in 2023. The agendas and presentations
by experts for 23 public meetings are available on the website. As a
past member of the PACCARB, I suggest this resource as not only a way
to hear from experts in the field of antibiotic resistance, but also as
a bridge to many additional resources in this field. My exposure to the
other members of PACCARB, and to the experts who gave their time to
educate us, showed me that we have some truly talented and dedicated
people working on antibiotic resistance.
---------------------------------------------------------------------------
\9\ U.S. Department of Health and Human Services. Office of the
Assistant Secretary for Health. Presidential Advisory Council on
Combating Antibiotic-Resistant Bacteria (PACCARB). https://www.hhs.gov/
ash/advisory-committees/paccarb/membership/index.html Accessed 7-8-
2023.
Thank you for the invitation to be present today. I look forward to
questions and discussion.
______
Senator Markey. Thank you, doctor, so much. And now I am
going to introduce Dr. Helen Boucher. Dr. Boucher is the Dean,
as well as Professor of Medicine at Tufts University School of
Medicine and the Chief Academic Officer of Tufts Medicine
Health System in Boston, Massachusetts.
She is a practicing infectious disease physician and not a
Wildcat, but a Jumbo. She also serves as Director of the
Stewart Levy Center for Integrated Management of Antimicrobial
Resistance.
In 2015, Dr. Boucher was appointed to the Presidential
Advisory Council on combating antibiotic resistance bacteria.
Dr. Boucher, you may proceed.
STATEMENT OF HELEN BOUCHER, DEAN AND PROFESSOR OF MEDICINE,
TUFTS UNIVERSITY SCHOOL OF MEDICINE, BOSTON, MA
Dr. Boucher. Thank you, Chairman Markey, Ranking Member
Marshall, and distinguished Members of the Subcommittee. Thank
you for holding a hearing on antimicrobial resistance and for
inviting me to testify on behalf of the Infectious Diseases
Society of America, in my capacity as Dean of the Tufts
University School of Medicine.
As an ID physician, I see firsthand how AMR and the dearth
of new antimicrobials is harming patients. AMR is everyone's
crisis and everyone's responsibility. I will briefly outline
key drivers of AMR, why AMR is one of the most significant
health crises of our time, and urgently needed solutions. As
Dr. Apley pointed out so beautifully, AMR is pathogen's ability
to evolve to resist antibiotics, making those drugs
ineffective. Resistance occurs in nature.
Antimicrobial overuse in humans, animals, and the
environment speeds resistance. Antimicrobials are unique in
that use in one individual can impact efficacy in the rest of
the population.
Despite some progress, antibiotics continue to be misused.
In 2016, about half of hospitalized patients were prescribed
antibiotics, and 30 to 50 percent of those prescriptions were
inappropriate. Environmental factors are also accelerating AMR.
Climate change, pollution, wildfires, and denser population
settings can all facilitate the spread of AMR through
waterborne pathogens, infected burns, and increases in
respiratory infections.
In 2019, an estimated 1.27 million deaths worldwide were
directly caused by AMR, and AMR played a part in nearly 5
million deaths. U.S. health care costs linked to infections
from six of the biggest AMR threats total more than $4.6
billion annually, with $1.9 billion of these costs borne by
Medicare.
Antimicrobials enable modern medicine. Advances like cancer
chemotherapy, organ transplants, hip replacement, C-sections,
and other complex care carry a risk of infection and are only
possible with antibiotic support.
AMR puts all these therapies to which Americans are
entitled at risk due to our lack of novel antimicrobials. I
specialize in caring for patients undergoing organ
transplantation. These patients must be on immunosuppressive
medicines to prevent rejection. Inability to eradicate or
control an infection precludes transplantation, and infection
following transplant is a leading cause of death in this
population. I have had the sad duty of caring for a person with
an infection caused by a resistant bacteria for which we had no
effective antibiotic.
He was unable to proceed to the transplant he needed and
had to go home on hospice, ultimately leaving his two young
sons fatherless. AMR is also impacting healthy individuals in
our communities. I have cared for otherwise healthy women with
resistant urinary tract infections that are no longer treatable
with oral antibiotics.
This has required 2 weeks of intravenous antibiotic
therapy, often started in the hospital and prolonged time away
from work and school. The opioid epidemic is also fueling AMR.
Individuals who inject drugs are 16 times more likely to
experience an invasive MRSA infection.
AMR disproportionately affects communities of color and
other marginalized populations. AMR is a national security
threat. Its bioterrorist agents may be engineered to resist
antimicrobials, and military service people are at heightened
risk for infected wounds. IDSA appreciates the HELP Committee's
leadership on AMR.
We thank Ranking Member Marshall and Senator Blumenthal for
spearheading an annual letter urging Congress to provide
funding to support improved AMR surveillance, prevention, and
research, but we must address gaps. The most important thing
the Subcommittee can do is advance a policy to establish a pull
incentive, such as a subscription model, to spur the discovery
and development of novel antimicrobials.
A subscription model would pay for these antimicrobials
based on their value instead of volume to drive private
investment in antimicrobial R&D. The President's budget request
proposes such a model and over 200 organizations support this
approach. R&D incentives must be paired with resources for
stewardship.
Stewardship programs optimize antimicrobial use, improve
patient outcomes, and lower health care costs. Unfortunately,
many health care facilities lack the resources necessary for
stewardship. The ID workforce that is needed to confront AMR is
in crisis. Patients with serious infections do better when they
are treated by an ID physician, but nearly 80 percent of U.S.
counties lack an ID physician, and only 56 percent of ID
physician training programs filled their positions in 2023.
Financial barriers hinder recruitment, something I
personally grapple with as a dean. ID physicians are among the
lowest paid specialist. Congress must help ensure the
availability of the ID workforce by improving reimbursement,
addressing student debt, and providing resources for training
and early career development.
Thank you so much for your attention to the critical issue
of AMR.
[The prepared statement of Dr. Boucher follows.]
prepared statement of helen boucher
Chairman Markey, Ranking Member Marshall and distinguished Members
of the Subcommittee, thank you for holding a hearing on the critical
issue of antimicrobial resistance (AMR) and for inviting me to testify
on behalf of the Infectious Diseases Society of America (IDSA) and in
my capacity as dean of Tufts University School of Medicine. As an
infectious diseases physician who has been in practice for 30 years, I
see firsthand how AMR is erasing our hard-won medical gains, making
health care procedures less safe, undermining our readiness for
bioterror events and public health emergencies, and routinely harming
healthy people in our communities. AMR is everyone's crisis and
everyone's responsibility.
I specialize in caring for patients undergoing organ transplants.
Organ transplantation is undoubtedly one of the miracles of modern
medicine. In 2021, 41,354 organ transplants were performed in the
United States, an increase of 5.9 percent over 2020 and the first time
the annual total exceeded 40,000. The three organ types most commonly
transplanted are kidneys (24,669), livers (9,236) and hearts (3,817).
Liver transplant totals have set annual records for the past 9 years
and heart transplants have set a new record each of the past 10 years.
Patients who have received a transplant are typically highly complex
and often have multiple underlying conditions or medicines that put
them at greater risk for contracting an infection. For example, these
patients must be on immunosuppressing medicines to help prevent their
bodies from rejecting their organs. Antibiotic-resistant infections are
increasingly threatening this lifesaving therapy. Inability to
eradicate or control an infection precludes transplantation and
infection following transplant is a leading cause of death in this
special population. I have had the sad duty of caring for a person with
an infection caused by a resistant bacteria for which we had no
effective antibiotic therapy. He was unable to have the transplant he
needed and had to go home on hospice, ultimately leaving his two young
sons fatherless. My ID colleagues across the country have all
experienced similar cases, and while they are not yet extremely common,
they are happening with greater frequency and will become even more
common if we do not act urgently to address AMR.
IDSA represents more than 12,000 infectious diseases (ID)
physicians, scientists and other health care and public health
professionals specializing in infectious diseases. Sadly, my colleagues
throughout the country and globally are seeing more and more patients
with multidrug-resistant infections.
IDSA has been sounding the alarm about AMR since 2004 with the
release of our ``Bad Bugs, No Drugs'' report. While the Federal
Government has made important strides to strengthen our response to AMR
with a One Health approach that covers human health, animal health,
agriculture and the environment, significant work remains to protect
patient safety and national security and to safeguard modern medicine
as we know it.
I will outline the key drivers of AMR, why AMR is one of the most
significant health crises of our time, the current state of AMR
response efforts and urgently needed solutions, including a
subscription model to provide a predictable return on investment for
novel antimicrobial research and development that is de-linked from the
volume of antimicrobials used and aligned with strong antimicrobial
stewardship.
The Drivers of AMR
AMR refers to pathogens' natural ability to evolve to resist the
effects of antimicrobial drugs, ultimately making those drugs
ineffective. While resistance occurs in nature, the overuse and misuse
of antimicrobials in humans, animals and the environment greatly
increases the speed at which resistance develops, significantly
shortening the time for which antimicrobial drugs remain effective and
reducing the number of useful antimicrobials. Antimicrobials are unlike
any other therapeutic in that use in one individual can impact efficacy
in the rest of the population.
Overuse and misuse of antimicrobials in any setting--human
medicine, animal health, agriculture, the environment--drives the
development of resistance. A One Health approach to combating AMR is
critical. We must improve surveillance, data collection and
antimicrobial stewardship--the appropriate use of antimicrobials--in
all settings to reduce AMR and its devastating impact on human health.
Despite some progress, antibiotics continue to be misused and
overused. 2016 estimates indicate that about half of hospitalized
patients were prescribed antibiotics, with 30 percent-50 percent of
those prescriptions estimated to be inappropriate or unnecessary. \1\
It is important to note that the increasing complexity of health care,
with greater numbers of highly complex procedures and new treatments
that increase risk of infection, also contributes to high levels of
antimicrobial use--antimicrobial use that is appropriate and necessary.
---------------------------------------------------------------------------
\1\ https://academic.oup.com/cid/article/63/12/1/2282817.
COVID-19 led to even greater antibiotic use, particularly during
the early days of the pandemic when clinicians were faced with
significant uncertainty about the disease and very few, if any,
treatment options. In addition, our sickest COVID-19 patients on
ventilators were at significantly increased risk for secondary
bacterial and fungal infections. From March-October 2020, about 80
percent of patients hospitalized with COVID-19 received antibiotics,
and we now know that much of this antibiotic use was unnecessary. \2\
---------------------------------------------------------------------------
\2\ https://www.cdc.gov/drugresistance/covid19.html#:-
:text=Antibiotic.
Antibiotic misuse and overuse are prevalent in outpatient settings
as well. CDC has estimated that at least 28 percent of antibiotics
prescribed in the outpatient setting are unnecessary, meaning that no
antibiotic was needed at all. \3\ Outpatient antibiotic prescribing
decreased overall during the COVID-19 pandemic, but prescribing rates
still vary widely across the U.S., with some states in the South having
prescribing rates more than double the rates in states in other
regions. \4\ Antibiotics were frequently prescribed for COVID-19. A
study published in the Journal of the American Medical Association
(JAMA) reported that among Medicare beneficiaries who had an outpatient
visit for COVID-19 in the first year of the pandemic, more than 30
percent received an antibiotic. \5\
---------------------------------------------------------------------------
\3\ https://pubmed.ncbi.nlm.nih.gov/32484505/.
\4\ https://www.cdc.gov/antibiotic-use/stewardship-report/
current.html.
\5\ https://jamanetwork.com/journals/jama/fullarticle/2791077
A variety of environmental factors are also accelerating the
development and spread of AMR, as outlined by a February 2023 United
Nations report. \6\ Climate change, pollution, more extreme weather,
wildfires, flooding and denser population settings can all facilitate
the spread of AMR. As the Earth warms, increased temperatures increase
the rate of bacterial growth and the rate at which antimicrobial
resistance genes spread between microorganisms. \7\ Severe flooding,
which is becoming more frequent due to climate change, can increase the
risk of illness caused by waterborne pathogens. For example, studies
have found higher levels of pathogenic bacteria and antibiotic
resistance genes in floodwaters and soil in the Houston area following
Hurricane Harvey. \8\, \9\ Flooding can also lead to conditions of
overcrowding and poor sanitation, further facilitating the spread of
infections, including multidrug-resistant infections. Burns from
wildfires can easily become infected, and inhalation of smoke and other
pollutants can worsen respiratory conditions, increasing the risk of
serious infection.
---------------------------------------------------------------------------
\6\ https://www.unep.org/resources/superbugs/environmental-action.
\7\ https://www.nature.com/articles/s41558-018-0161-
6.epdf?sharing-token=c0EPIqc1pgNRhnrU0M59SdRgN0jAjWel9jnR3ZoTv0Pa0XQPUYl
H2uhflOAVxx1GDk6ya-mYSorzT7YJqTi4iBni-
y1nPhU8zgyJxgKGXHM0GJbwQwZz0psTSUavsspIEB-u8oX1DPJWk6N-
1QqbGPWqzKrFp9SRh3lb7-TSwjevMNDBFSpZaoLzuEKdDa7Ys39IYFhjqUWSgOhZASHA--
3D--3D&tracking-referrer=www.cnn.com.
\8\ https://pubs.acs.org/doi/10.1021/acs.estlett.8b00329.
\9\ https://pubmed.ncbi.nlm.nih.gov/33077230/.
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AMR: Unraveling Modern Medicine
It is essential that we address AMR because resistant infections
are killing millions of people every year and putting modern medicine
in serious jeopardy. In 2019, an estimated 1.27 million deaths
worldwide were directly caused by AMR, and AMR played a part in nearly
5 million deaths. This makes AMR a leading cause of death globally.
\10\ The post-antibiotic era is not just a looming threat--for many
patients it is already here. AMR is a crisis not only for the
individual patients impacted but for our entire health care system.
National health care costs linked to infections from six of the biggest
AMR threats are estimated to be more than $4.6 billion annually. \11\
$1.9 billion of these costs are estimated to be borne by Medicare. \12\
---------------------------------------------------------------------------
\10\ https://www.thelancet.com/journals/lancet/article/PIIS0140-
6736(21)02724-0/fulltext.
\11\ https://www.cdc.gov/drugresistance/solutions-initiative/
stories/partnership-estimates-healthcare-cost.html.
\12\ https://academic.oup.com/cid/article/74/6/1070/6374434.
We must protect antimicrobials because antimicrobials enable and
sustain modern medicine. Most medical advances carry a risk of
infection and rely upon antimicrobials. Consider procedures like cancer
chemotherapy, organ transplants, hip and knee replacements, Cesarean
sections, and other surgeries and complex care. All of these procedures
save and enhance human lives, and they all carry risk of infection.
Clinicians are only able to provide this care because they have safe
and effective antimicrobials to prevent and manage infectious
complications. But as our antimicrobial arsenal diminishes, our modern
medical gains are unraveling, and patients are facing devastating
---------------------------------------------------------------------------
consequences. Consider a few examples:
Cancer: Cancer and many cancer treatments can weaken
the immune system. Infections are a primary or associated cause
of death in 50 percent of patients with cancer, as AMR can make
these infections difficult or impossible to treat. \13\ Sadly,
I and my colleagues have seen patients cured of cancer succumb
to infections caused by resistant bacteria.
---------------------------------------------------------------------------
\13\ https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/
caac.21697.
Maternal mortality: Sepsis--the body's overwhelming
and life-threatening response to untreated infections that can
result in organ failure and death--is the second leading cause
of pregnancy-related deaths. AMR exacerbates the risk of sepsis
by making infections much more difficult to treat. Between 2014
and 2017, infection or sepsis caused 12.7 percent of pregnancy-
related deaths in the United States. Pregnancy-related
infections that can lead to sepsis can be related to
miscarriages, C-sections, prolonged or obstructed labor, and
mastitis (breast infection). \14\
---------------------------------------------------------------------------
\14\ https://www.sepsis.org/sepsisand/pregnancy-childbirth/.
Biologics: Certain biologics that are used to treat a
wide range of conditions weaken the immune system, making
---------------------------------------------------------------------------
individuals more susceptible to infections.
Implantable medical devices: Prosthetic joints,
pacemakers, implantable defibrillators, ventricular assist
devices for patients with serious heart disease, and other
implantable devices can easily become infected. In many cases,
removal of these devices may be impossible or impractical, and
patients may face recurring or chronic infections that can
become increasingly resistant.
Opioid use: The opioid epidemic is also fueling the
spread of resistant infections, including life-threatening
heart valve infections, skin and soft tissue infections, bone
and joint infections, and more. The Centers for Disease Control
and Prevention (CDC) estimates that individuals who inject
drugs are 16 times more likely to experience an invasive
methicillin-resistant S. aureus (MRSA) infection. \15\ This is
particularly frightening as the opioid crisis continues to
worsen. In my state of Massachusetts, data announced last month
indicated that the opioid-related overdose death rate in
Massachusetts increased to 33.5 per 100,000 people in 2022, 2.5
percent higher than in 2021 and 9.1 percent higher than the
pre-pandemic peak in 2016.
---------------------------------------------------------------------------
\15\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045815/
#:?:text=Data--20from--206--20sites20of,develop20invasive--20MRSA--
20infections--20than.
Fungal infections: In March 2023, CDC warned that
cases of Candida auris, a difficult-to-treat resistant fungal
pathogen, have been increasing steadily since they were first
reported in 2016. C. auris is resistant to multiple antifungal
drugs, spreads easily in health care facilities and has high
mortality rates. \16\
---------------------------------------------------------------------------
\16\ https://www.cdc.gov/media/releases/2023/p0320-cauris.html.
Organ transplants: More than 42,000 organ transplants
were performed in the U.S. in 2022, a 3.7 percent increase over
2021 and a new annual record. \17\ Unfortunately, AMR and the
dwindling arsenal of antimicrobial drugs available to support
these patients means many of them face death due to infection
despite a successful transplant.
---------------------------------------------------------------------------
\17\ https://unos.org/news/2022-organ-transplants-again-set-
annual-records/.
Cystic fibrosis: People with cystic fibrosis (CF)
face a heightened, life-long risk of infections because of the
thick sticky mucus in their lungs. Routine use of antibiotics
in CF care is medically necessary; however, too many people
with cystic fibrosis find themselves battling difficult-to-
treat infections for which existing antibiotics are not
---------------------------------------------------------------------------
effective.
Increasing resistance is forcing physicians to turn to older, more
toxic antibiotics like colistin--a drug that causes serious kidney
damage. Patients are left with the unfathomable choice of dying from
their infection or taking an antibiotic that could leave them in need
of dialysis for the rest of their life or a kidney transplant. The
rapid spread of the transferable gene, mcr-1, which confers colistin
resistance, threatens the efficacy of even colistin--a last resort drug
for the treatment of many drug-resistant bacterial infections. \18\ We
must do better.
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\18\ https://www.nature.com/articles/s41429-023-00622-1.
---------------------------------------------------------------------------
AMR in the Community
AMR is also impacting healthy individuals in the community. Rates
of a type bacteria that cause resistant urinary tract infections or
UTIs (extended-spectrum beta-lactamase [ESBL]-producing
Enterobacteriaceae) increased by more than 50 percent from 2013 to
2019. \19\ In fact, increasing numbers of patients with UTIs that were
once easily treated with oral antibiotics now require intravenous (IV)
antibiotics in the hospital--increasing our health care costs and
creating serious disruptions to patients' lives. In my practice, I have
cared for otherwise healthy women with urinary tract infection caused
by ESBL-producing organisms. This has required 2 weeks of intravenous
antibiotic therapy, often started in the hospital, and prolonged time
away from work or school.
---------------------------------------------------------------------------
\19\ https://www.cdc.gov/drugresistance/pdf/threats-report/2019-
ar-threats-report-508.pdf.
---------------------------------------------------------------------------
As another example, an ongoing outbreak of drug-resistant eye
infections due to contaminated eye drops has killed or caused blindness
and the need for removal of the eye, a devastating and disfiguring
complication, in several patients. This underscores that resistant
infections are a threat to us all and that we must invest in the tools
necessary to ensure we can manage such outbreaks with limited negative
impacts.
Sexually transmitted infections like gonorrhea and syphilis that
were once easily treated with antibiotics are becoming increasingly
drug resistant.
AMR and Health Inequities
Like so many health conditions, AMR disproportionately impacts
historically marginalized populations, though more comprehensive data
is needed to fully understand the inequitable impacts of AMR. A few
examples:
Community-associated MRSA rates are higher among
Black populations when compared to White populations. \20\
---------------------------------------------------------------------------
\20\ https://www.cdc.gov/drugresistance/pdf/health-equity-
antibiotic-resistance-fs-508.pdf.
American Indian and Alaska Native persons have
substantially higher population rates of all invasive Group A
streptococcus disease. \21\
---------------------------------------------------------------------------
\21\ https://www.cdc.gov/drugresistance/pdf/health-equity-
antibiotic-resistance-fs-508.pdf.
In February 2023, CDC published a health alert on an
increase in extensively drug-resistant (XDR) Shigella
infections. Historically, Shigella has largely impacted
children under age 5. There is now an increase in Shigella
infections among men who have sex with men, individuals
experiencing homelessness, international travelers and people
with HIV. \22\
---------------------------------------------------------------------------
\22\ https://emergency.cdc.gov/han/2023/han00486.asp.
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AMR: A Threat to Readiness and National Security
The AMR crisis was further exacerbated by the COVID-19 pandemic. In
2020, U.S. hospitals experienced a 15 percent increase in AMR
infections and deaths, though pandemic-related data gaps suggest that
the total national burden of AMR may be much higher. Experts do not
expect a return to pre-pandemic levels without concerted action. \23\
Any emergency resulting in high levels of hospitalization, particularly
high levels of ventilator use and overwhelmed hospital staff, creates a
ripe opportunity for the spread of secondary drug-resistant infections.
---------------------------------------------------------------------------
\23\ https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-
508.pdf.
Addressing AMR is also important for bioterror readiness and
national security, as agents used by bioterrorists may be genetically
engineered to resist current antimicrobials. \24\ The World Health
Organization (WHO) has estimated that if 50 kg of Y. pestis were to be
released as an aerosol over a city with a population of 5 million,
150,000 people might fall ill with pneumonic plague, 36,000 of whom
would die. \25\ Drug-resistant strains of Y. pestis have been reported,
which can increase mortality. \26\ As another example, modeling
suggests that deliberate release of aerosolized F. tularensis over
London would result in an estimated 130,000 infections and 24,000
deaths. \27\ Natural resistance is already observed in tularemia, and
the overuse of fluoroquinolones, one of the main treatments for this
infection, in the last two decades has led to treatment failure and
relapses in tularemia patients. \28\
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\24\ https://books.google.com/
books?hl=en&lr=&id=IiGEDwAAQBAJ&oi=fnd&pg=PR1&ots=ZXqKRYXnRH&sig=39-
Vf6uaisjn-zSVfBI-1p-9TT4#v=onepage&q&f=false.
\25\ https://apps.who.int/iris/bitstream/handle/10665/39444/
24039.pdf.
\26\ https://journals.asm.org/doi/full/10.1128/AAC.00306-06.
\27\ https://www.liebertpub.com/doi/abs/10.1089/bsp.2011.0004.
\28\ https://ami-journals.onlinelibrary.wiley.com/doi/full/
10.1111/j.1751-7915.2008.00063.x.
Military service people, who are often critical first responders in
emergencies, can be at heightened risk for resistant infections, as
combat wounds and burns can easily become infected. In the current
conflict in Ukraine, patients are presenting with highly complex,
multidrug-resistant musculoskeletal infections from gunshot and bomb
wounds. Physicians identified multiple pathogens, including Klebsiella
pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, E. coli
and fungal pathogens. Infections showed high rates of resistance to
some of our most powerful antibiotics: 72 percent were resistant to
carbapenems and newer cephalosporins (ceftazidime-avibactam and
ceftolozane-tazobactam), 39 percent were resistant to cefiderocol, 20
percent to colistin and 96 percent to ciprofloxacin. \29\ International
travel makes it very easy for drug resistant pathogens to spread across
the globe.
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\29\ https://www.cidrap.umn.edu/antimicrobial-stewardship/
clinicians-describe-challenge-treating-multidrug-resistant-war-wounds.
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Insufficient Antimicrobial Pipeline
Despite the urgent and increasing need for novel antimicrobials to
treat resistant infections, the current pipeline has fewer than 50
antibacterial therapeutics in clinical development worldwide--only a
handful of which are for the most threatening gram-negative pathogens--
a critical area of need. \30\ Given that most drugs in development do
not ultimately secure FDA approval, and that there is a wide array of
drug-resistant bacteria and fungi for which new therapies are needed,
the current pipeline is grossly inadequate. The last FDA approval of an
antibiotic was in November 2019.
---------------------------------------------------------------------------
\30\ https://www.who.int/publications/i/item/9789240047655.
Novel antimicrobials must be used appropriately by prescribers with
sufficient expertise to limit the development of resistance; this means
ensuring that these precious medicines are not overused. This is
essential from a clinical and public health perspective but creates a
serious barrier to private sector investment in antimicrobial
innovation. Currently, Federal and commercial payers reimburse for
antimicrobials when they are used, so judicious use to preserve
effectiveness severely limits the ability of an antimicrobial developer
---------------------------------------------------------------------------
to earn a return on their investment.
Between 2010 and 2019, 18 new antibiotics were approved by FDA,
which is an improvement from the 11 new antibiotics approved from 2000-
2009. However, only one of those 18 antibiotics had a new mechanism of
action, and it was the first such antibiotic approved since the 1980's.
\31\ This underscores the need not only to strengthen antimicrobial
research and development but more specifically to incentivize the
development of truly novel antimicrobials.
---------------------------------------------------------------------------
\31\ https://www.bio.org/sites/default/files/2022-02/The-State-of-
Innovation-in-Antibacterial-Therapeutics.pdf.
Federal support from the Biomedical Advanced Research and
Development Authority (BARDA) and the National Institute of Allergy and
Infectious Diseases (NIAID) has been critically important to the
development of more recently approved antibiotics, and their funding
for CARB-X has strengthened the pre-clinical antimicrobial pipeline.
However, we see plain evidence of failures in the market for
antimicrobials: There has been a disturbing number of instances in
which small companies successfully bringing a new antibiotic to market
are then pushed to file for bankruptcy due to the broken antimicrobials
market that provides little to no opportunity to earn a return on
investment. This can lead to the loss of U.S. patient access to these
antimicrobials. There is an urgent need for a creative solution that
will revitalize and sustain novel antimicrobial innovation and
availability.
Antimicrobial Stewardship
Antimicrobial stewardship programs in hospitals aim to optimize
antibiotic use to ensure that patients receive the right drug for the
right bug with the right dosing and duration. These programs have been
found to improve patient outcomes, reduce inappropriate antibiotic use
and lower health care costs. \32\, \33\ nationwide, 98 percent of
hospitals report having implemented all seven of the core elements of
antimicrobial stewardship recommended by CDC \34\ and as required by
the Joint Commission and the Centers for Medicare and Medicaid Services
(CMS). Despite this important progress, there remain many important
opportunities to improve antimicrobial therapy and reduce inappropriate
antibiotic use in hospitals.
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\32\ https://academic.oup.com/cid/article/66/7/995/4851152.
\33\ https://pubmed.ncbi.nlm.nih.gov/27246783/.
\34\ https://www.cdc.gov/antibiotic-use/stewardship-report/
current.html.
While many hospitals can meet stewardship requirements on paper,
they often lack the resources and experienced staff necessary to fully
implement medically recommended stewardship protocols and to extend the
benefits of stewardship to all patients. Studies have found consistent
gaps between necessary levels of physician and pharmacist staffing and
existing staffing levels. A 2018 study found that each 0.50 increase in
physician and pharmacist full-time employee (FTE) support for a
stewardship program predicted a 1.48-fold increase in the odds of the
program demonstrating effectiveness. \35\
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\35\ https://doi.org/10.1093/cid/ciy255.
The COVID-19 pandemic further stressed hospital budgets, diverting
resources from stewardship programs despite the unprecedented need for
stewardship to manage high levels of antibiotic use among hospitalized
patients with COVID-19. \36\ In many hospitals, stewardship teams led
the complex administration of COVID-19 therapeutics, which was an
appropriate use of limited human capital resources given their
expertise. This work included evaluating treatments for COVID-19 in
clinical trials, developing treatment guidelines and educating
providers as data rapidly evolved, partnering with state and local
health departments, assessing patient risk factors to prioritize
limited quantities of therapeutics, and devising innovative strategies
to reach rural and other underserved populations. These efforts were
crucial to reducing COVID-19 hospitalizations and deaths but came at
the expense of traditional antimicrobial stewardship.
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\36\ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375214/.
Even in Massachusetts, where we have a robust health care system,
there are many hospitals and health care facilities that lack adequate
stewardship infrastructure and resources, human and financial, that are
needed to deliver this important part of clinical care.
AMR Surveillance and Data Collection
We need to better understand where resistance is happening and how
antimicrobials are being used to better target prevention and treatment
strategies. The CDC National Healthcare Safety Network (NHSN) includes
the Antibiotic Use and Resistance (AUR) module, which collects and
provides actionable data to inform and evaluate efforts to optimize
antibiotic use. More than 2,400 acute care hospitals across the United
States had submitted at least 1 month of antibiotic use data as of
August 2022. Of those hospitals, 2,283 reported in the past 12 months
(July 2021--June 2022). This represents a significant increase in
reporting in the last several years, but gaps in data persist and more
comprehensive reporting will better inform the current state of AMR in
the U.S.
CMS included a requirement for antibiotic use and resistance
reporting in their fiscal year 2023 Inpatient Prospective Payment
System final rule. IDSA supports this requirement, which will help
ensure that antibiotic stewards, clinicians and key decision-makers
have access to more comprehensive antibiotic use data, enabling us to
track antibiotic use and resistance over time, evaluate stewardship
interventions, identify best practices and improve antibiotic use. It
is critical that health care facilities not yet reporting antibiotic
use and resistance data be provided resources necessary to begin
reporting. It is also critical to provide CDC with resources necessary
to support NHSN users, analyze and share data, and promote health
professional education and appropriate antibiotic use.
Workforce Needed to Combat AMR
The ID workforce that is needed to respond to AMR is in crisis. ID
physicians and other ID health care and public health professionals are
needed to care for patients with resistant infections, lead
antimicrobial stewardship and infection prevention and control
activities, and conduct surveillance and research, including clinical
trials. Data consistently show that for patients with serious
infections and conditions complicated by infections (e.g., transplants,
cancer, etc.), ID physician care improves outcomes, decreases
mortality, shortens hospital stays and lowers health care costs. \37\,
\38\
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\37\ https://academic.oup.com/jid/article/216/suppl-5/S588/
4160394.
\38\ https://academic.oup.com/cid/article/58/1/22/372657.
Workforce shortages coupled with lower pay and a lack of financial
incentives for recruitment and retention persist among ID health care
professionals, including ID physicians, clinical microbiologists,
nurses, pharmacists, physician assistants and infection preventionists.
As pharmaceutical companies leave the antimicrobials market, we are
suffering a significant ``brain drain'' with far too few scientists
with expertise in ID. I personally grapple with this challenge in my
role as dean of Tufts University School of Medicine. Our MD and PA
graduates increasingly select more lucrative specialties like surgery
or dermatology rather than infectious diseases, further adding to the
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already fragile workforce.
In 2022, nearly 80 percent of U.S. counties lacked an ID physician,
\39\ and only 56 percent of ID physician training programs filled their
positions for the 2023 appointment year, compared to most other
physician specialties for which nearly all of their programs filled
their positions. \40\ A quarter of health care facilities have reported
a vacant infection preventionist position, and a 2019 survey showed a
vacancy rate for clinical microbiologists of more than 10 percent.
Communities without ID health care professionals are less equipped to
respond to AMR.
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\39\ https://www.acpjournals.org/doi/10.7326/m20-2684.
\40\ https://www.nrmp.org/wp-content/uploads/2023/04/2023-SMS-
Results-and-Data-Book.pdf.
IDSA has conducted extensive outreach and mentoring to medical
students and residents, and we routinely find high levels of interest
in the field of ID, but financial challenges consistently pose barriers
to recruitment. ID physicians are among the lowest paid medical
specialists, earning even less than general internal medicine
physicians who lack the additional years of training that an ID
physician undergoes. \41\ High levels of student debt often
understandably drive physicians to higher paying specialties, leaving
our Nation without enough experts to combat AMR. The ID specialty is at
an inflection point, and without action to recruit, train and retain
the next generation of ID specialists, we can expect to see an increase
in mortality due to infectious diseases for years to come.
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\41\ https://www.medscape.com/slideshow/2022-compensation-
overview-6015043?icd=login-success-email-match-norm.
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Solutions
IDSA is grateful for the HELP Committee's long history of
leadership on AMR, including passage of the Generating Antibiotic
Incentives Now (GAIN) Act in 2012 and enactment of the Limited
Population Antibacterial Drug (LPAD) review mechanism in 2016 as part
of the 21st Century Cures Act, which helped improve the regulatory
environment for the study and evaluation of new antibiotics and
antifungals to address unmet needs in limited patient populations.
The National Action Plan for Combating Antibiotic-Resistant
Bacteria (CARB) was launched in 2015 and provided an important
framework for a coordinated, comprehensive Federal response to AMR. The
second iteration of the plan was released in 2020 and largely aims to
build upon the progress made since 2015. The five goals of the plan,
which IDSA supports, are: (1) slow the emergence of resistance and
prevent resistant infections; (2) improve One Health surveillance; (3)
advance development and use of diagnostics; (4) advance research and
development of antibiotics, other therapeutics and vaccines; and (5)
improve international collaboration. We greatly appreciate Ranking
Member Marshall and Senator Blumenthal's leadership of an annual letter
urging Congress to provide sufficient funding to BARDA, CDC and NIAID
to advance critical AMR efforts. These resources have supported
improved surveillance, clinician education about AMR, research and
innovation, and it is critical that funding for these efforts
continues. Through our Tufts Levy Center for Integrated Management of
Antimicrobial Resistance, I and my colleagues gratefully receive
funding from NIAID to innovate in clinical trials through the NIH
Antibacterial Resistance Leadership Group (ARLG), investigate new
therapies, and advance stewardship and prevention efforts.
In addition, the Presidential Advisory Council on Combating
Antibiotic-Resistant Bacteria (PACCARB), on which I served, convenes
key experts to provide a diverse array of perspectives to help inform
Federal AMR response activities. The PACCARB's recommendations have
allowed Federal efforts to benefit from a wide range of expertise, and
the PACCARB should be reauthorized so this important work may continue.
It is also critical that we address gaps in existing efforts,
specifically with regard to antimicrobial innovation, stewardship and
the AMR workforce. The PACCARB released a March 2023 report,
``Preparing for the Next Pandemic in the Era of Antimicrobial
Resistance,'' and recommended urgently needed efforts to strengthen
antimicrobial stewardship, infection prevention and control, the ID
workforce, data sharing and medical countermeasure innovation. \42\
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\42\ https://www.hhs.gov/sites/default/files/paccarb-pandemic-
preparedness-report.pdf.
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Subscription Model to Finance Novel Antimicrobial Research &
Development
To build on current Federal AMR efforts the single most important
thing this Subcommittee can do is advance a policy to establish a pull
incentive, such as a subscription model, to finance the discovery and
development of novel antimicrobials. This approach would have a
transformative impact on antimicrobial innovation, revitalizing the
discovery and development of truly novel antimicrobials by providing a
predictable, reasonable return on investment for novel antimicrobials.
The Federal Government already pays for antimicrobials through various
health programs including Medicare, Medicaid, Tricare and Veterans
Affairs (VA), but it pays in a way that fails to incentivize innovation
and appropriate use. Conversely, a subscription model is smart spending
that would pay for the value rather than volume. Under a subscription
model, the Federal Government would enter into contracts with
antimicrobial developers to pay predictable fees for a steady supply of
a novel antimicrobial. This approach would help drive more private
investment to antimicrobial research and development and help ensure
that novel antimicrobials developed with critical support from BARDA,
NIAID and CARB-X remain available to U.S. patients.
It is particularly important to front-line ID clinicians like me
that incentives are designed to deliver truly novel antimicrobials that
provide important clinical benefits for patients.
Equally important, incentives for antimicrobial development must be
paired with policies to support appropriate use of antimicrobials by
providing urgently needed funds to health care facilities to support
their antimicrobial stewardship programs.
The President's Budget Requests for fiscal year 2023 and fiscal
year 2024 have proposed a subscription model to strengthen
antimicrobial innovation and stewardship and more than 200
organizations representing health care professionals, public health,
patients, scientists, advocates and industry have endorsed this
approach.
AMR Workforce Investments & Physician Reimbursement
In addition, Congress must take steps to ensure the availability of
the expert ID workforce needed to combat AMR, including ID physicians,
ID physician-scientists, clinical microbiologists, infection
preventionists, pharmacists and nurses. We must make ID a financially
feasible choice for health care professionals by addressing student
debt, improving reimbursement, and providing sufficient resources for
training and early career development. Specific recommendations
include:
Enhance Medicare reimbursement for ID physicians,
through one or more of the following approaches: Increase the
value of the codes most frequently billed by ID physicians
(i.e., inpatient evaluation and management codes); provide a
Medicare incentive payment for ID physicians (e.g., similar to
the Medicare incentive payments for primary care physicians and
general surgeons); and create new mechanisms to pay for
critical population health activities to combat AMR that
benefit the general patient population, but are not necessarily
directly tied to the care of an individual patient (e.g.,
leading stewardship programs, infection prevention and control
programs, and outpatient parenteral antimicrobial therapy or
OPAT programs).
Fund implementation of the Bio-Preparedness Workforce
Pilot Program to incentivize individuals to pursue careers in
ID in health professional shortage areas. IDSA greatly
appreciates that Senators Baldwin (D-WI), Collins (R-ME), Rosen
(D-NV) and Murkowski (R-AK) spearheaded the authorization of
this pilot as part of the PREVENT Pandemics Act last year.
Increase NIAID funding to support training and early
career ID and AMR researchers. IDSA greatly appreciates the
annual appropriations letter led by Ranking Member Marshall (R-
KS) and Senator Blumenthal (D-CT) to support funding for this
and other AMR efforts across HHS.
Once again, on behalf of IDSA, thank you very much for your
attention to the critical issue of antimicrobial resistance and for
inviting me to testify. IDSA looks forward to working with you and your
colleagues to advance the solutions necessary to confront the AMR
crisis, protect modern medical gains and save lives.
______
Senator Markey. Thank you, doctor, so much. And next, we
are going to hear from Ms. Melanie Lawrence.
Ms. Lawrence is a Massachusetts resident and health care
advocate living with cystic fibrosis. Ms. Lawrence serves on
committees for the Cystic Fibrosis Foundation, Boston
Children's Hospital, and Cystic Fibrosis Learning Network.
She is also a recipient of the Alex Award, the highest
award that CF Foundation gives for her volunteer work to help
and support people with cystic fibrosis. Whenever you feel
comfortable, please begin, Ms. Lawrence.
STATEMENT OF MELANIE LAWRENCE, HEALTHCARE ADVOCATE, FAIRHAVEN,
MA
Ms. Lawrence. Thank you so much. Good morning, and thank
you, Chairman Markey, Ranking Member Marshall, and
distinguished Members of the Subcommittee for inviting me here
to testify.
My name is Melanie Lawrence. I am 43 years old, living with
cystic fibrosis. While I am here to speak to you about my
experience with infection, drug resistant bugs are not a
problem exclusive to people living with CF.
This is a human issue, and last I checked, we are all
humans. They are a problem that all Americans will face if we
don't find a solution to jumpstart innovation in antimicrobial
development. CF is a rare genetic disease affecting nearly
40,000 people in the U.S. that causes the body to produce
sticky mucus in the lungs, heightening the risk of infection.
When I was diagnosed, my parents were told that my life
expectancy would be 16 years old. Today, the median life
expectancy for people with CF has increased to 56, but there is
still no cure. CF is only a part of who I am though, it does
not define me.
I am a single mother to a most amazing 12 year old son. I
am a daughter, a sister, a friend, a proud aunt, and I am
passionate about making sure that patients like me, and others
have access to treatment they need to have fulfilling lives, as
well as in a health care system that is rooted in humanity.
Every day I spend hours taking medications, doing physical
therapy, exercise, meditation, breathwork, all while raising a
very active 12 year old, trying to create as many meaningful
memories with him as I can. Despite being proactive, infections
due to drug resistant Pseudomonas, MRSA--or MRSA, impact, my
health and I have relied heavily on antibiotics my whole life.
Earlier, I could trust that a two-week antibiotic course of
oral antibiotics would do the trick. This meant--as the
bacteria in my lungs began outsmarting the antibiotics, I also
needed IV antibiotics to keep my infections under control.
This meant a two-week stay in a hospital, and I would have
to have antibiotics administered through a pick line, threaded
up the vein in my arm. By 18, I needed a larger dose of IV
antibiotics for up to 5 weeks at a time. Losing hope, I
participated in a clinical trial for IV Tobramycin, which ended
up causing chronic tinnitus, a severe kidney damage, and I was
ultimately removed from the study because of it.
Over the next two decades, antibiotic resistance became a
bigger threat to my health, as did the subsequent side effects
of more potent antibiotics. My airways became so damaged that I
began having hemoptysis, which is bleeding in my lungs. I also
began developing blood clots. Because of that, my only option
for IV antibiotics became a temporary IV line placed through my
jugular vein. It was no longer possible to eradicate the
bacteria, so the goal was to keep my head above water.
Now, in my 40's, the bacteria in my lungs are resistant to
nearly every antibiotic, except for Tobramycin, which I cannot
take because it is so toxic to my already damaged kidneys and
hearing.
My focus is to manage my symptoms and maintain the best
quality of life possible. Without the security of effective
antibiotics to help me heal, I find myself living with chronic
fear and anxiety about when the bacteria residing in my lungs
will act up or when another infection will take me away from
truly living.
On a deeper level, I am often navigating a humbling loss of
control, loss of autonomy, and a deep, subconscious fear of
death. Of leaving my son without his primary caregiver, the
person who knows him best and loves him without abandon, his
mom.
My body is both my biggest ally, keeping me alive and
fighting off these infections, whilst also being my biggest
threat, trying to kill me from the inside. And yet, living with
CF has been a gift, not a curse. It has opened my eyes to the
fragility of time and the importance of connection, and that is
a gift we should all be so lucky to receive while we are
healthy and able to appreciate it rather than when it is too
late.
My story is not an uncommon experience in the CF community,
nor is it unique to people with CF. Bacteria are abundant and
it is inevitable that more Americans will encounter resistant
infections. It is not a question of if you can catch them, it
is a question of when. Without new antibiotics, the bacteria
will win this war.
I thank the Subcommittee for giving me the opportunity to
share my story and ask that you work together to find
innovative policy solutions for patients like me and for all
Americans like the PASTEUR Act.
Personally, I would love to see my son graduate college or
even to become a grandparent, something that I have never even
allowed myself to imagine because it feels so out of reach
without new antibiotics. Time is ticking, and we need your
help. Thank you.
[The prepared statement of Ms. Lawrence follows.]
prepared statement of melanie lawrence
Good morning. Thank you, Subcommittee Chairman Markey, Ranking
Member Marshall, and distinguished Members of the Senate Primary Health
& Retirement Security Subcommittee, for inviting me to testify before
you today. My name is Melanie Lawrence, I am 43 years-old, and I am
living with cystic fibrosis (CF). I am grateful to be part of this
Subcommittee's discussion on a subject that I am unfortunately all too
familiar with, antimicrobial resistance. While I am here to speak to
you about my experiences with infection, drug-resistant bugs are not a
problem exclusive to people living with CF--they are a problem for
everyone. People with CF provide a glimpse into a future that everyone
will experience if we don't address this growing threat. As I share
more about my experience, I ask that you consider the public health
risks that all Americans face if we do not jumpstart innovation and
develop new, more effective antimicrobials as soon as possible.
I was diagnosed with CF at age 5. At the time, my parents were told
that my life expectancy was 16 years old. When I turned 16, the median
life expectancy had grown to 31 years old--and now, at age 43, it is 56
years old.
As you are aware, cystic fibrosis is a life-threatening genetic
disease that causes persistent lung infections and makes it very
difficult to breathe, often leading to respiratory failure. More than
40,000 people in the United States live with CF and there is no known
cure. People with CF face a heightened, life-long risk of infections,
and often rely on antibiotics as part of their daily care. Still, all
too many--like me--battle antibiotic resistant infections for which
there are no effective treatment options available.
However, cystic fibrosis is only a part of who I am and it does not
define me. I am a single mother to the most amazing 12-year-old son. I
am a daughter, a sister, a friend, a proud aunt, and a passionate
contributor to the greater good. I believe that it is my life's purpose
to connect with others and remind the healthcare industry that patients
are human beings with full, complex lives outside of the exam room who
deserve to be treated as such. I find my work serving on volunteer
committees with the Cystic Fibrosis Foundation, the Cystic Fibrosis
Learning Network, and patient advisory boards extremely rewarding. I am
grateful for the opportunities to give back and improve how health care
is delivered and how providers think about patients--as people first. I
love being out in nature and catching the sunrise, I am a hot yoga
enthusiast and enjoy challenging myself wherever possible.
Sadly, I have lost many friends to CF-related infections over the
years, some dying before their 21st birthday. Many other CF friends
continue to struggle with the management of their symptoms. I believe
the stable health I do have is a combination of luck, new therapies,
and hard work. Each and every day I spend hours taking medications,
doing physical therapy, exercise, meditation, and breathwork--all while
raising a very active 12-year-old and trying to create as many
meaningful memories with him as I can while I am physically able to do
so.
Since I was a teenager, I have participated in as many clinical
trials and research studies as I can. Despite significant medical
advances and new therapies that have helped stabilize my health, lung
infections due to multi drug-resistant Pseudomonas aeruginosa and
Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are the
chronic complications of CF that impact my life the most.
Chronic respiratory infections continue to be a hallmark of living
with CF because of the persistent mucus in the lungs of people with the
disease. More than 60 percent of people with CF culture positive for at
least one chronic pathogen in their lungs starting from a very young
age and that figure climbs to over 80 percent among adults living with
CF. Like me, nearly 20 percent of CF adults have chronic infections
caused by pseudomonas and 25 percent of people with CF will culture
MRSA each year.
As a result, I have relied on antibiotics my whole life. Throughout
my childhood and early teenage years, antibiotics were highly
effective. Each time I caught a cold or contracted an infection, I
could trust that a two-week course of antibiotics would have me feeling
better and back to living life as usual. By age 13, the bacteria in my
lungs were already outsmarting oral antibiotics and I needed
intravenous (IV) antibiotics once a year in addition to oral
antibiotics to keep my infections under control. The IV antibiotics
were administered via a peripherally inserted central catheter (PICC)
line--an IV that was threaded into a vein up my arm. For the next 5
years, IV antibiotics were administered in the hospital one to two
times each year and required me to stay in the hospital for 2 weeks,
often missing school and many holidays with my family. My hospital
refers to this time as ``cleanouts'' when CF patients would have a two-
to-five-week course of IV antibiotics and respiratory therapy to help
prevent exacerbations and lengthier hospital stays as a result of
infection.
By age 18, a two-week course of IV antibiotics was no longer enough
to combat the bacteria growing in my lungs. I needed larger doses of IV
antibiotics for up to 5 weeks at a time. This took place partially
inpatient at the hospital and partially during regular hospital visits.
Looking for a better solution, I participated in a clinical trial for
IV Tobramycin that ended up being so damaging to my kidneys
(nephrotoxic) that I was prematurely removed from the study. That trial
also resulted in constant tinnitus (high-pitched ringing in my ears)
that I still have, and will continue to have every minute, of every
day, for the rest of my life.
In my twenties, antibiotic resistance became a bigger issue as did
the subsequent side effects the more potent antibiotics caused. As the
bacteria became resistant to antibiotics, I began to lose many of the
``tools'' in the toolkit to combat drug resistant bugs and treating my
lung infections. It was also the decade where my lung infections first
began leading to hemoptysis, or the coughing up of blood from my lungs.
Sometimes the bleeding can be so severe and life-threatening that I
need a medical procedure called an arterial embolization to block the
bleeding arteries. The bleeding in my lungs can then become a breeding
ground for bacteria, resulting in a vicious cycle of infections. Due to
these complications, I need antibiotics more frequently and for longer
periods of time than typically prescribed.
By age 30, I began having chronic upper extremity blood clots and
could no longer receive IV antibiotics via a PICC line. The blood clots
also made me a poor candidate for a port, a device that can be inserted
as an alternative delivery method for antibiotics over a long course of
treatment for people with CF. My only option for IV antibiotic
treatment was to get a temporary IV threaded through my jugular vein
During this time, the bacteria in my lungs became so resistant that one
antibiotic alone did not stand a chance. I needed to take a combination
of two to three antibiotics at a time just to keep my infections at
bay. However, even multiple antibiotics couldn't eradicate the bacteria
in my lungs, they just bought me time and allowed me to get my head
above water.
Now in my forties, the bacteria in my lungs are resistant to nearly
all antibiotics except for Tobramycin, which I cannot take because it
is so toxic to my already-damaged kidneys and hearing. There is no
eradicating the bacteria in my lungs and the recurrent infections have
led to permanent scarring in my lungs along with pockets of collapse.
My focus is now on managing my symptoms and maintaining the best
quality of life possible. Every single antibiotic I try results in
insufferable side effects that require me to take additional drugs to
counteract them, or I am forced to discontinue the course early because
they make me feel so miserable. The side effects vary and impact my
body as well as my mental health. They cause rashes, kidney damage,
depression and everything in between. Today's antibiotics are not
nearly the friendly savior I used to depend upon, and I regularly have
to ask myself which is worse: the infection or the side effects?
These challenges have led to a more stressful life experience for
not only me, but for my son, my family, and my friends as well. In the
past, infections were stressful, but we knew that there was an ``easy
fix'' with a quick course of antibiotics. Now, it feels like much more
of a gamble with my life. For me, something as simple as the common
cold can take months to rebound from and often turns into pneumonia. I
no longer have the security of relying on antibiotics to help me heal,
so I live with chronic fear and anxiety about when the bacteria
residing in my lungs will act up or when another infection will take me
away from the moments I cherish for a few months or the even the simple
daily tasks that we often take for granted. Ultimately, on a deeper
level, I am always navigating a humbling loss of control, loss of
autonomy, and a deep subconscious fear of death--and mostly, of leaving
my son without his primary caregiver--the person who knows him the best
and loves him without abandon. His mom.
I live in a constant state of introspection--both mind and body. Up
to this point, much of my life has depended on me being attuned with my
body and hyper-aware of what my body is trying to tell me. This year,
I've learned that this has caused me more anxiety than I wanted to
admit. I realized I had an inability to be still or to sit with my body
in silence. My body is both my biggest ally, keeping me alive and
fighting off infection, whilst also being my biggest threat, trying to
kill me from the inside.
Yet, I am not a victim by any means, and I am committed to doing
everything in my power to stay as healthy as I can for as long as I
can. Living with CF has been a gift, not a curse. It has opened my eyes
to the fragility of time and the importance of connection, and that is
a gift we should all be so lucky to receive while we're healthy and
able to appreciate it, rather than when we're dying and it's too late.
I am a big believer in the mind/body connection so I work hard at
staving off the threat of lung exacerbations as much as I can. I
combine both Western and Eastern medicine, work with a therapist to
keep my anxiety low, practice mindfulness, meditate, do breathing
exercises, and lead a healthy lifestyle. I wash my hands constantly,
take vitamins, get rest, and constantly assess the risk vs. benefit of
social interactions. My friends know to disinvite me to events if
someone is sick and are mindful of my germ exposure. It has become
second nature for my son to sanitize his hands every day when he gets
out of school. He doesn't complain when we have to leave a party early
because mom is tired, and he understands when he has to skip a birthday
party or social gathering because the germ risk is too high. It pains
me that he's had to grow up in a more heightened state of awareness,
but I like to think he's more empathetic because of it.
For me, my family and all people living with CF, it can be a
challenge to navigate social risks because a part of feeling alive is
joining in social events. We want to travel, we want to go to the
movies, we want to go to concerts, and we want to attend family
gatherings in the winter even though the flu is circulating. We want to
feel alive and actively participate in life just like you do. Life is
for living after all.
This is my story, my experience of what it's been like to live with
antibiotic-resistant bacteria. While my life may look quite differently
from yours, it is not an uncommon experience in the CF community. And
while right now it may seem like it is unique to people living with CF,
these bacteria are abundant and it is inevitable that more people will
encounter antimicrobial resistant bacteria. It is not a question of if
you can catch them, but when.
I am grateful for organizations like the Cystic Fibrosis Foundation
that recognize the significant threat antimicrobial resistance poses to
the CF community, and in 2018 created the Infection Research Initiative
as part of a sweeping effort to advance infection research. To date,
the Foundation has committed over $140 million to the initiative
because they know that for people with CF--and all of us--to lead full
lives our providers need more tools in their toolbelts. They need more
antibiotics. Better antibiotics. Full stop.
We have all relied on antibiotics at some point in our lives and
how lucky are we that they've been available and effective for many of
us? But the bacteria are outsmarting us and without new and novel
alternatives, they will win this war. Private sector investments alone
won't solve the problem. We need the Federal Government to lead and
support innovative policy solutions with an all of the above approach
to help people like me live long enough to see our children thrive.
Personally, I want to see my son graduate college or even become a
grandparent--something I've never even allowed myself to imagine
because it feels so out of reach without new antibiotics.
I thank the Subcommittee for giving me the opportunity to share my
story and I ask that you work to help find solutions for patients with
a heightened risk for infection like me, and for all Americans, as you
consider legislation this Congress.
______
Senator Markey. Beautiful. Thank you. Senator Marshall,
would you introduce the next witness?
Senator Marshall. All right. Thank you, Mr. Chairman. I
want to introduce Ms. Christine Miller, who is testifying on
behalf of the Antimicrobials Working Group in the Biotechnology
Innovation Organization. Ms. Miller is the CEO of the Melinta
Therapeutics, a biopharmaceutical company that specializes in
novel, broad spectrum antibiotics to help patients in hospital
and community settings.
With a background and chemical engineer, Ms. Miller has
spent over 20 years championing life sciences innovations,
working for small companies to some of the leading innovators
in the world.
Ms. Miller will shed light on why the commercial
marketplace for antibiotics in the United States is at serious
risk of collapsing, something my colleagues tell me over and
over again. The risk of collapsing due to ongoing reimbursement
challenges and supply chain shortages.
Again, my friends back home tell me this every day I go
back home, and I talk to my friends, still practicing. She is
going to share why small companies are now responsible for over
95 percent of global novel antimicrobial development, and even
then they face bankruptcy in the coming years.
Thank you so much for agreeing to testify and share your
story, Ms. Christine Miller.
STATEMENT OF CHRISTINE ANN MILLER, PRESIDENT & CHIEF EXECUTIVE
OFFICER, MELINTA THERAPEUTICS, NEW YORK, NY
Ms. Miller. Thank you, Chairman Markey, Ranking Member
Marshall, and distinguished Members of the Subcommittee. Thank
you for the opportunity to speak with you today.
My name is Christine Miller. I am President and CEO of
Melinta Therapeutics, and Melinta is a small biotech providing
innovative therapies to people impacted by acute and life
threatening illnesses.
My story begins in New York with two amazing parents who
immigrated here from Jamaica. The women in my family dedicated
their careers to helping patients. My mother, a registered
dietitian, worked at Montefiore Hospital. And as a child, I
remember visiting her at the hospital, watching her solve
patients' problems.
I was inspired to pursue a career in pharmaceuticals when I
realized I could use my education, like the women of my family,
to help patients. This is why being here today is so important
to me. I want to help identify the unmet need of patients and
address the issues of availability and access to lifesaving
antimicrobial medicines.
Antimicrobial drugs are the cornerstone of modern medicine.
These drugs are critical to effectively deliver medical care
for patients receiving chemotherapy, organ transplants, and
patients undergoing routine surgical procedures like hip
replacement and C-sections. However, bacteria and fungi are
living organisms that adapt and evolve over time and become
resistant to antimicrobials, a phenomenon known as
antimicrobial resistance, or AMR.
In the United States, AMR is a third leading cause of death
behind heart disease and cancer. Things have gotten worse since
the pandemic. In 2020, hospital acquired drug resistant
infections and deaths jumped 15 percent as COVID erased years
of progress in the fight against superbugs.
While drafting my testimony, I was reminded of a story from
a patient, Sue Paxton. Sue, who was a recipient of a successful
liver transplant, who also found out she had a severe fungal
infection when hospitalized. After multiple rounds of
antifungals and further deterioration of her condition, Sue and
her doctor were able to gain early access to rezafungin, a
novel antifungal developed by Cidara Therapeutics that Melinta
will launch later this month.
Within days, Sue was on the path to recovery.
Unfortunately, what happened to Sue happens all too often in
hospitals, and the only way to combat these life threatening
infections is to continually innovate newer, safer
antimicrobials, and ensure that patients have access to these
innovations.
It is important to understand that we do not have an
innovation problem. The U.S. Government recognized the need and
has taken action to support research and development needed to
address resistant infections. Programs like CARB-X have done an
amazing job and reinvigorating the pre-clinical pipeline. Also,
programs through BARDA have been vital to combat AMR.
Melinta is a partner in a public, private collaboration
with BARDA to advance two FDA approved antibiotics for use in
pediatric patients and for use against biothreat pathogens. We
also do not have an approval problem. Congress already enacted
a policy to streamline regulatory approval for antimicrobials.
Companies are getting innovative products approved but are
failing after launch. What we do have is a commercial
marketplace problem that is fundamentally unique to
antimicrobials, driven by reimbursement and access challenges.
As a result, many biotech companies run out of money in the
quest to provide patients with access to lifesaving therapies.
Unless we see changes to the post-approval side of the
equation, the ability to bring these products to patients
remain in jeopardy.
The good news is that Congress and the Federal Government
are in the position to solve this problem. Policies to increase
access to new antimicrobials through reforms to antimicrobial
reimbursement and novel payment mechanisms called pull
incentives that decouple payment from the volume of
antimicrobials used are urgently needed now.
Without changes to the system, we will continue to see
access challenges and further deterioration of the innovation
pipeline, and patients, our family members, our neighbors will
continue to die.
My hope for today is that this Committee views all of
today's testimony as a call to action to fix the commercial
marketplace. AMR remains a silent killer in hospitals every
day. Every year we wait to address this crisis is another year
more patients are at risk for losing their lives.
Thank you for your attention to this public health crisis,
and I look forward to your questions.
[The prepared statement of Ms. Miller follows.]
prepared statement of christine ann miller
I--Opening Remarks
Chairman Markey, Ranking Member Marshall, and distinguished Members
of the Committee, thank you for the opportunity to speak with you
today. My name is Christine Miller, and I am President and Chief
Executive Officer (CEO) of Melinta Therapeutics. Melinta is a small,
innovative biotechnology company providing life-saving therapies to
patients impacted by acute and life-threatening illnesses. In addition
to my role as CEO, I serve as Chair of the Antimicrobials Working
Group--or AWG--a coalition of emerging antimicrobial companies
committed to improving the commercial environment for drug development.
Melinta is also a member of the Biotechnology Innovation Organization
(BIO), the largest trade organization representing biotechnology
companies, academic institutions, state biotechnology centers and
related organizations in the U.S. and 30+ countries.
My story begins in the New York, the product of two amazing parents
who immigrated from Jamaica. I grew up in a family where the women were
all in healthcare as either nurses or dietitians and dedicated their
careers to helping patients. My mother, a Registered Dietitian, worked
at Montefiore Hospital for 38 years. I remember visiting her at the
hospital as a child and watched her solve patients' problems. I too
have always been passionate about problem solving and applied that to
degree in Chemical Engineering. I was inspired to pursue a career in
pharmaceuticals when I realized I could use my education, like my
mother and the women of my family to help patients. Everything that I
have tried to do in my 20 plus year career is about creating access for
patients so that they can get the medicines they need. That's why being
here in front of you is so important to me. I want to help identify the
unmet need of patients and providers and address the issue of how we
can create the access needed to live-saving antimicrobials medicines.
Put simply, antimicrobial drugs are the cornerstone of modern
medicine. These drugs are critical for the effective delivery of
medical care more broadly for patients receiving chemotherapy, organ
transplants, and even those undergoing routine surgical procedures like
hip replacements and cesarean sections. However, bacteria and fungi
adapt and evolve over time and become resistant to these treatments--a
phenomenon known as ``antimicrobial resistance,'' or AMR for short.
Overuse and misuse of current antibiotics accelerates AMR. For example,
in the outpatient settings, the CDC estimates that one-third of
antibiotics are used improperly. \1\ This rise in AMR is rapidly
rendering our antimicrobial arsenal ineffective and represents a
problem in the here and now--it will also continue to get progressively
worse over time. As AMR becomes more prevalent, many medical procedures
that are commonplace today will become too risky to undertake, with
catastrophic consequences to medical care, including death.
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\1\ https://www.cdc.gov/media/releases/2016/p0503-unnecessary-
prescriptions.html.
As I was drafting my testimony today, I was reminded of a story
from one of our patients--Sue Paxton. Sue, who is a resident of Manakin
Sabot, Virginia, was the recipient of a successful liver transplant,
and while hospitalized, found out she had a severe fungal infection.
After multiple rounds of antifungals and further deterioration of her
condition, Sue and her infectious disease physician were able to gain
early access to rezafungin, a novel anti-fungal developed by Cidara
Therapeutics and that Melinta will launch later this month, and within
a few days, Sue was on the path to recovery. When I asked Sue, a mother
and grandmother about her experience, she was extremely grateful to her
medical team that they were knowledgeable about the latest in the field
and could help her get access to the innovative medicine she needed. I
was moved, when she said, ``It was a live-saving drug for me, I
wouldn't be here without it''. New, innovative, and effective
antimicrobials used in the hospital setting are critical to saving
lives like Sue's--and her story is a testament to the importance of
---------------------------------------------------------------------------
today's hearing.
Unfortunately, what happened to Sue happens all too often in
hospitals. The only way to combat these life-threatening infections is
to continually innovate newer, safer antibiotics, and to ensure their
access and appropriate use. AMR is a ``silent pandemic'' in the
American healthcare system. In my testimony today, I hope to convey how
serious a threat AMR is to our Nation, and why the challenges
surrounding this issue have become so difficult for our health system
to overcome.
The problem right now is that our Nation's physicians lack the
access needed to prescribe these innovative products, and in turn,
patients are not receiving the care that they need. This broken
ecosystem for antimicrobials has created an unviable marketplace that
renders innovative drugmakers unable to develop the products needed to
catch up--and keep up--with the growing threat of resistance.
From an industry perspective, antimicrobial development is uniquely
different than any other area of biotechnology. Unlike a disease area
like oncology, it is very rare for a patient to know exactly what type
of infection they have and exactly what drug they are being given.
Remember, also, that antibiotics are intended to be used sparingly
and only until the infection has resolved to prevent further
exacerbation of resistance. What this means for industry is that many
companies have tended to focus on other novel product areas, such as
chronic diseases, where there is a more stable and long-term market for
therapies. It is not surprising then that the vast majority of research
being done in the antimicrobial space today is led by small companies
like ours, and not large pharmaceutical firms.
Many are familiar with the concept of the ``valley of death''--the
period between promising lab research and clinical trial launch when
biotech companies run out of funding. It takes 10-15 years to develop
one successful drug, and despite significant investments in time and
money, 90 percent of drug candidates fail in clinical trials fail,
never reaching regulatory approval. \2\, \3\ The antimicrobials sector
faces another unique obstacle, what many of my colleagues have termed
the ``second valley of death'', which occurs after FDA approval. In
most areas of biotech, the period after FDA approval is a time for
celebration for both providers and patients. Unfortunately, for the
antimicrobials sector, it can take years for newly approved therapies
to actually reach patients. This is due in part to the flawed
reimbursement structure for antimicrobials, which disincentives
hospitals from giving physicians access to the newest, safest, and most
appropriate drug. This is also due to the unique way that innovative
antimicrobials are held in reserve in the hospital setting to guard
from exacerbating resistance.
---------------------------------------------------------------------------
\2\ https://www.nature.com/articles/d41573-021-00190-9.
\3\ https://www.nature.com/articles/nrd.2016.136
Since antimicrobials companies are unable to recoup their
investment under traditional volume-based payment structures for drugs
alone, many are unable to remain commercially viable and end up failing
shortly after launch. The loss of a company in the antimicrobials
sector does not just represent an economic loss. In some cases, it
represents the loss of intellectual property to foreign adversaries and
the outflow of talent and scientific expertise. This, in turn, results
in industry specific skilled workforce challenges, commonly known as
---------------------------------------------------------------------------
``brain drain.''
Most importantly, the loss of these companies poses an existential
risk to patients. Without immediate solutions, the antimicrobial
development industry will wither away, and we will face a daunting
future without effective antibiotics, where commonplace procedures and
infections can become fatal.
I am here today to characterize the unique problem facing the
antimicrobial sector.
We do not have an innovation problem. Recognizing the
need for novel antimicrobials to address resistant infections,
the U.S. Government has taken action to support the critical
research and development of these important therapies. U.S.
Government programs like CARB-X have successfully funded over
90 early stage clinical candidates and diagnostics.
We do not have an approval problem. In 2012, Congress
enacted a policy to streamline regulatory approval for
antimicrobials to address serious and life-threatening
infections. As I mentioned earlier, companies are getting
innovative products approved, but are failing after launch.
This has a ripple effect that has a chilling impact on the
pipeline of drugs in development.
What we do have is a commercial marketplace problem--
driven by reimbursement and access challenges--that is
fundamentally unique to antimicrobials. Without reforms on the
post-approval side of the equation to increase access to new
antibiotics--through reforms to antimicrobial reimbursement and
novel payment mechanisms called ``pull incentives'' that
decouple payment from the volume of antimicrobials used--
hospitals will continue to be forced to rely on older
medications. Without changes to this system, we will continue
to see further deterioration of the innovation pipeline, and
patients--grandmothers, children, fathers, mothers, our
neighbors--will continue to die.
The good news is that Congress and the Federal Government are in a
position to solve this problem. There are already policy solutions that
could make a significant impact to correct the broken antimicrobial
marketplace in both the short-term to sustain patient access and in the
long run to ``pull'' other novel products across the finish line and
ensure they reach patients.
My hope for today is that this committee views the collective
expertise of this panel as a ``call to action'' to address AMR both as
the threat it poses to our public health and to our Nation's
preparedness in the event of future biosecurity threats such as
pandemics, and as the silent killer in hospitals every day.
II. AMR Is a Societal Issue of Mass Scale
The patients our novel antimicrobials can save have no bounds--
children with cancer, a marathon runner post routine surgery, a new
mother delivering a child via c-section. It does not take a lifetime of
antibiotic exposure to fall victim to a resistant infection that can
change your life, or a loved one's life forever. In 2023 alone, a
number of superbug outbreaks have gripped the attention of health
experts, the media, and the public. \4\
---------------------------------------------------------------------------
\4\ Superbugs Are Here The Time to Act is Now. BIO. Infographic.
Candida auris is a fungus that can cause serious
bloodstream, skin, and other infections and is often multi-drug
resistant--and has caused recent outbreaks in healthcare
settings. In 2021, there were nearly 1,500 clinical cases of
Candida auris in the United States--more than a 300 percent
---------------------------------------------------------------------------
increase since 2019.
Pseudomonas aeruginosa is a strain of bacteria that
can cause infections in the lung or blood or other parts of the
body post-surgery and is often drug resistant. This year,
contaminated eyedrops caused severe Pseudomonas aeruginosa
infections in at least 68 patients in 16 states, including 8
who suffered permanent vision loss, 4 who needed surgical
removal of their eyeball, and 3 deaths.
Shigella are bacteria that cause the infection
shigellosis, which often manifests itself as a stomach bug.
Extensively drug-resistant strains of shigella are on the rise.
5 percent of Shigella cases in 2022 were extensively drug-
resistant--up from 0 percent in 2015.
As mentioned previously, AMR threatens to undermine the major
advances in medicine made over the last 90 years. Globally, AMR has
become a leading cause of death having killed over 1.2 million people
in 2019 and played a part in nearly 5 million deaths that year. \5\ In
the United States, AMR was associated with over 173,000 deaths in
2019--the third leading cause of death, behind only heart disease and
cancer. \6\ By 2050, AMR infections will result in over 10 million
deaths per year globally. The economic impact on the United States will
also be substantial--a $20 billion per year cost to the U.S. healthcare
system and $35 billion annual loss in productivity. \7\
---------------------------------------------------------------------------
\5\ Global burden of bacterial antimicrobial resistance in 2019: a
systematic analysis. Murray, Christopher J L et al. The Lancet, Volume
399, Issue 10325, 629-655.
\6\ https://vizhub.healthdata.org/microbe/.
\7\ https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-09-508.pdf.
The burden of AMR has become even more prominent since the start of
the COVID-19 pandemic and threatens future responses to biosecurity
threats. In 2020, hospital-onset drug-resistant infections and deaths
jumped 15 percent as COVID-19 erased years of progress in the fight
against superbugs. AMR also threatens to undermine other areas of
medicine. One report cites that infections are a primary or associated
cause of death in 50 percent of patients with cancer.'' \8\
---------------------------------------------------------------------------
\8\ O'Neill, J. ``Tackling Drug-Resistant Infections Globally:
Final Report and Recommendations,'' 2016.
Recognition of these alarming trends and a realization that safer
and more novel products are needed have led Congress to take a series
---------------------------------------------------------------------------
of actions over the years to address AMR.
In 2012, Congress passed the Generating Antimicrobial Incentives
Now (GAIN) Act to promote the development of new antimicrobial products
known as Qualified Infectious Disease Products, or QIDPs, intended to
address ``unmet medical need'' for the ``most serious and life-
threatening infections.'' \9\ Passage of the GAIN Act was intended to
spur antimicrobial innovation. However, it has fallen short in
``pulling'' novel drugs to approval, and even more importantly,
ensuring patients have access to those drugs once they are approved.
---------------------------------------------------------------------------
\9\ Nanayakkara, AK, Boucher, HW, Fowler, VG, Jezek, A, Ouerson,
K, Greenberg, DE. Anbioc resistance in the patient with cancer:
Escalating challenges and paths forward. CA Cancer J Clin. 2021: 71:
488-504. https://doi.org/10.3322/caac.21697.
The Federal Government also implemented additional incentives to
support the research and development of new drugs, such as the CARB-X
program under the Biomedical Advanced Research and Development
Authority (BARDA). These programs have been resoundingly successful in
their mission and have become vitally important to antimicrobial
---------------------------------------------------------------------------
development.
Subsequent to these important steps, and as stated earlier--
We do not have an innovation problem
We do not have an approval problem
What remains is a commercial marketplace problem underpinned by
systemic post-approval and reimbursement challenges which must first be
acknowledged, and then corrected for.
III. State of Innovation of the Antimicrobials Pipeline
Antimicrobial drug development is at an all-time low. Unlike other
areas of biotechnology, where investors typically see high returns upon
a drug's FDA approval, antimicrobial products are used sparingly and
can take years to see appropriate uptake in a clinical setting.
Oncology companies raised close to $7 billion in 2020 (up 900 percent
from 2011), whereas antibiotic companies raised just $0.16 billion
(less than what they raised 10 years prior). \10\ For drugs in human
testing, there are about four dozen antibiotics currently undergoing
trials compared to more than a thousand cancer drugs. \11\
---------------------------------------------------------------------------
\10\ Jonathan J Darrow , Aaron S Kesselheim, Incentivizing
Antibiotic Development: Why Isn't the Generating Antibiotic Incentives
Now (GAIN) Act Working?, Open Forum Infectious Diseases, Volume 7,
Issue 1, January 2020, ofaa001, https://doi.org/10.1093/o.d/ofaa001.
\11\ The State of Innovation in Anbacterial Therapeutics. BIO
Industry Analysis. February 2022.
Small biotech companies remain committed to bringing novel drugs
across the finish line. More than 60 companies and non-profit research
institutes are developing the 64 clinical-stage drug candidates to meet
the growing need for differentiated antibacterials. In recent years,
small companies accounted for 80 percent of novel antimicrobial drug
discoveries, with 8 percent being discovered by non-profit institutes
and universities, and only 12 percent originating from large companies.
\12\ In terms of characterizing the entire R&D engine, there remains a
$150 billion cumulative revenue gap since 2001 for on-patent global
antibiotic sales, an unheard-of trend in any other area of
biotechnological development. \13\
---------------------------------------------------------------------------
\12\ Kevin Outterson Testimony to House Energy & Commerce
Committee. 28 April 2023.
\13\ The State of Innovation in Anbacterial Therapeutics. BIO
Industry Analysis. February 2022.
---------------------------------------------------------------------------
IV. Innovation Without Implementation
The answer to fixing the commercial marketplace for these drugs is
not as simple as inventing new therapies. First, the principle of
antimicrobial stewardship dictates that antibiotics should be used only
when appropriate and should always be the foremost consideration in
care. Nevertheless, there are a combination of factors that lead to
slow uptake and a lack of implementation in hospitals:
1. New AMR drugs when approved are most critical for inpatient
care, especially for hospital-acquired infections.
2. Hospitals are currently incentivized to hold in reserve, or
rely on cheaper, inferior generic antibiotics--a function of
how reimbursement for inpatient care, which is currently capped
by bundled payments set by CMS known as a diagnosis related
group (DRG), is
designed. As a result, generic antibiotics are used as first line
drugs, even when newer drugs may be more appropriate.
3. At the same time, companies see a weak demand for new
antibiotics. Low revenues fail to offset the high costs of
research and development, as well as costs to support
production, commercialization, and post-approval regulatory
requirements.
4. These market realities have led investors to flee antibiotic
development. The combined market capitalization of all publicly
traded antimicrobial companies is .01 percent of the top 10
global pharmaceutical companies.
As a result of these factors, numerous small biotech companies have
ceased operations in recent years. One example is a company that, less
than a year after approval, was forced to sell its assets to two
principal buyers based in China and India. \14\ In the past 2 years
alone, two other companies, both of which have drugs addressing CDC-
identified AMR threats--have faced extreme financial difficulties. \15\
---------------------------------------------------------------------------
\14\ Outterson. K. ``Trends in the Global Antibiotics Market.
Nature Reviews Drug Discovery 22, 174 (2023).
\15\ Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. New
York Times. 25 December 2019.
---------------------------------------------------------------------------
V. Solutions Are Needed to Right a Market in Free Fall
The Federal Government currently pays for antimicrobials in a way
that fails to drive innovation or appropriate use. The unique way that
innovative antimicrobial products are used requires fundamentally
unique solutions to address the broken marketplace for antimicrobial
innovation. Policy concepts that aim to achieve this goal include:
1. Fixing Reimbursement to Reflect the Market Dynamics Unique to
Antimicrobials
Addressing antimicrobial reimbursement is two-fold. Companies, like
mine--a clear and timely pathway to patient access and market uptake.
Also, we need to address barriers to entry that are preventing biotechs
from entering this space today. New, alternative payment models can
create that signal needed to drive research and development back to
this pipeline and catch-up in our battle against resistant infections.
First, we need to address hospital formularies head-on.
Currently, hospitals perceive that they lose money whenever a new
antimicrobial is introduced to their formularies, which in turn blocks
access to the therapy. However, numerous studies have demonstrated that
better patient outcomes are strongly associated with the use of newer
antimicrobial agents, meaning that patients who receive newer
treatments spend less time in the hospital. Several studies indicate
that the time to initiation of appropriate therapy is the key to
improved patient outcomes and saves lives.
In the past few years, the Centers for Medicare and Medicaid
Services (CMS) has introduced new tools to support antimicrobial
innovation. However, structural issues remain with these reimbursement
tools that continue to disincentivize hospitals from properly utilizing
novel antibiotics. Difficulties with hospital formularies under the DRG
payment structure in the inpatient system also represent a persistent
challenge. In general, reviewing reimbursement mechanisms for
antimicrobials and further educating providers about novel products
would help strengthen market uptake.
At the same time, we also need to implement novel antimicrobial
payment mechanisms i.e., `Pull Incentives'. To promote necessary
innovation in the antimicrobial industry, Congress should consider
novel pull incentives such as subscription models that pay for a
reliable supply of novel antimicrobials with payments that are
decoupled from volume of the product used. This type of novel payment
mechanism would incentivize the development of novel antimicrobials
based upon the value they provide for public health, rather than the
volume used. Such a model would directly support the appropriate use of
the antimicrobials it supports while also providing support for
antimicrobial stewardship programs (which improve patient outcomes,
reduce AMR, and save money) in rural, safety net and critical access
hospitals.
2. Reviewing Administrative Actions on AMR
In March of this year, the Presidential Advisory Council on
Combating Antibiotic-Resistant Bacteria (PACCARB) released an updated
report with clear recommendations to prepare for the next pandemic.
Congress should review these recommendations for relevant areas of
legislative action.
3. Strengthening Procurement and Late-Stage R&D for Novel
Antimicrobials
As mentioned previously, during any public health emergency--a
pandemic, terrorist attack, or natural disaster--secondary and
opportunistic AMR infections are likely to increase morbidity and
mortality in hospitalized patients. This is particularly important for
pandemic preparedness, where bacterial infections secondary to viral
pneumonia can be the primary driver of death, as was seen in the 1918-
19 Spanish Flu Pandemic. \16\
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\16\ An Antibiotics Biotech Begins Wind Down, Lays O. Nearly All
Works. Endpoints News. 6 January 2023.
Project BioShield, or PBS, was created in 2004 to accelerate the
availability of medical countermeasures (MCMs) to protect against
recognized threat agents. Administered by BARDA, PBS contracts fund
both late-stage development activities and drug procurement for the
Strategic National Stockpile (SNS). To date, BARDA has awarded two PBS
contracts to develop/procure small molecule antimicrobials to counter
bacterial biowarfare agents. \17\, \18\ These contracts provide a near-
term stabilizing effect to the recipient companies through procurement
sales and support for mandatory post-approval studies. It is important
to maintain and increase funding for PBS to align with current public
health needs, specifically for procuring antimicrobials as outlined in
BARDA's current Strategic Plan.
---------------------------------------------------------------------------
\17\ Fauci, et al. ``Predominant Role of Bacterial Pneumonia as a
Cause of Death in Pandemic Influenza: Implications for Pandemic
Influenza Preparedness''.
\18\ Venatorx Pharmaceucals Awarded BARDA Project BioShield
Contract. 3 October 2022.
---------------------------------------------------------------------------
VI--Conclusions
Thank you for this opportunity to testify and allowing me to share
the positions of small, innovative biotechnology professionals. Every
year we wait to address the crisis in the antimicrobial ecosystem is
another year patients like Sue Paxton and our dedicated healthcare
providers must wait to have access to life saving medicines.
Strengthening investments in our Nation's public health preparedness,
ensuring readily available stock of innovative antimicrobials in all
hospitals and transforming the way we pay for innovation of
antimicrobials is paramount to the health and security of our Country's
patients. AWG, BIO, and our member companies are committed to serving a
resource to the HELP as it works to address AMR and strengthen American
innovation.
______
Senator Markey. Thank you, Ms. Miller. Thanks to this great
panel. I will turn to questions from the Subcommittee. Ms.
Lawrence, as a cystic fibrosis patient, you know more than
anyone. CF patients are more prone to infection and must be
able to rely on antibiotics that are effective and that you
also have to be able to access and afford.
This on top of what can be dozens of pills a day for a CF
patient. So can you talk about the importance of developing new
antibiotics, Ms. Miller just talked about that, and making sure
those antibiotics are available and affordable for people like
you.
Ms. Lawrence. Yes. Thank you for the question, Chairman
Markey. I think that antibiotics are not the most expensive of
all of the drugs that I take. They are probably the most
affordable. I am a very avid participant in clinical research
to try to bring new drugs and therapies to market.
Of all the studies I have done over the decades, I have
only done one new antibiotic trial. And even though it did
result in lasting permanent side effects, I would do another
one in a heartbeat. It is just they are not--we don't have the
opportunities to find more antibiotics. So, it doesn't--it's
not so much as a cost issue, as it is an availability and
development issue.
Senator Markey. Thank you. Dr. Boucher, you are treating
patients in Boston every single day. You are seeing how bad the
opioid crisis has become. Tufts is right there at the center of
it in downtown Boston, and it puts people at risk of
antimicrobial resistance. So, can you explain to us why people
with opioid use disorder are at risk and how can we mitigate
that risk?
Dr. Boucher. Thank you for the question, Chairman Markey.
Yes, sadly, we saw data released about a week ago that in
Massachusetts, the opioid epidemic is at its worst, and we are
seeing increased numbers of patients with MRSA infections,
invasive infections.
The way these individuals get sick, it starts often with a
very simple thing, interruption of the skin. So, injection
interrupts the protective layer that the skin gives our body.
And people are colonized, the skin is colonized with the staph
bacteria that gets into their system.
What happens in these individuals is that they become sick,
or many of them are also malnourished, have other underlying
diseases, hepatitis C, other things, so treating them is
complicated. Many of them experience homelessness, so following
through on treatment is complicated.
They go into environments where they can spread the
infection. That propagates the problem, so it gets into more
social problems as well as medical problems. In the hospital,
these patients require greater care.
They need to be isolated in private rooms and we have to
protect ourselves so that we don't spread the infection to
other patients. It adds greatly to costs, to morbidity, and
mortality for those patients.
Senator Markey. Okay, great. Thank you. And there is no
silver bullet. Dr. Apley, could you tell us about the orchestra
of different entities that will be needed to work together in
order to prevent this crisis from spreading further?
Dr. Apley. Thank you, Chairman Markey. When I look at that,
the combination, it is infection prevention, which is very,
very, very important--a huge part of our efforts. Diagnostics.
We have challenges with having access to rapid diagnostic
tests.
As I understand from my days on PACCARB, we sometimes have
challenges getting reimbursed for the tests we do have that we
are able to put in.
Accurate tests, and then our antimicrobial susceptibility
testing interpretation and continuing to develop breakpoints
and more rapid tests for pathogen identification and
determining which antibiotics might be the best. Those are
really the main components.
The other thing is on both human and veterinary sides are
very, very focused initiatives on antimicrobial stewardship.
And this also gets into the realm of behavior as it relates to
antimicrobial prescribing.
Senator Markey. Okay. Thank you. And Ms. Miller, for
infectious diseases. Like Dr. Boucher, what is stopping them
from using the most innovative antibiotics that they have
decided would be best for their patients? What role does your
company and companies like it have in helping to ensure that
there isn't red tape in between the doctor and their patients?
Ms. Miller. Well, thank you for the question. So, companies
like ours, like Melinta, we are very much focused on creating
access anytime we can for patients. When we are working with
hospitals and hospital systems, it definitely is quite
complicated to get a new product on formulary. There is a bit
of a red tape, but our organization works tirelessly to make
sure that hospitals are aware of the new--the latest therapies
and provide them all the information that they need in order to
get our products onto hospital formularies.
However, what we do know is that hospitals are
disincentivized from putting new or innovative products on
their formulary and having their use because of the cost. It is
definitely more of an incentive because of the way
reimbursement works in the hospital for hospitals to use older,
cheaper generic drugs as front line versus using newer,
innovative products.
Senator Markey. Great. Thank you.
Senator Marshall.
Senator Marshall. Thank you, Chairman. I yield to Senator
Budd.
Senator Budd. Thank you, Ranking Member. Thank the Chairman
for having this hearing as well. Mrs. Miller, thank you all and
thank the whole panel for being here today. Ms. Miller, your
testimony mentions a period between lab research to clinical
trial launch as the valley of death, taking anywhere from 10 to
15 years and billions of dollars, as I understand it, before a
new antibiotic can come to market. So how can we build on
successful public, private partnerships like CARB-X to bring
more clinical antibiotic candidates to the market?
Ms. Miller. As I mentioned before, CARB-X has been really
great at reinvigorating the pipeline. Unfortunately, some of
those products are far from actually coming to market.
But BARDA has other programs, other private public,
partnerships that are helping to bring innovation to the
marketplace faster than if companies were trying to do that on
their own.
We just announced a recent partnership with BARDA for a
public--a private, public partnership. And what that will allow
us to do is bring innovation for pediatric patients to market
faster.
Senator Budd. Thank you for that. When I go on their
website for CARB-X, it shows a little under--a little over $300
million, little under $400 million that has been invested. What
attracted those dollars and how do we make that more, if it is
a good program?
Ms. Miller. Well, I think the first thing is focusing on
where is there unmet medical need, right. So, we see the
trends. We see where infections are higher, where resistance is
higher.
When companies can bring forward ideas to CARB-X for
funding, there is an opportunity there for collaboration. There
is also the need to focus on preparedness, right.
Not just the infections that we are battling today, but
what could be the infections in the future, the pathogens that
we need to be most concerned about from a bio threat
perspective. There are opportunities to collaborate there as
well.
Senator Budd. Thank you. Now, you also mentioned a second
to valley of death when the FDA approves a new drug, but
patients can't access it because hospitals keep physicians from
prescribing the newest therapies.
Can you go into more detail about the perverse incentives
that are out there that keep new therapies on the shelf instead
of being prescribed to patients? And then what reforms to the
GAIN Act should Congress pursue to bring more novel drugs
forward and to ensure patients have access to those drugs?
Ms. Miller. Well, I want to make sure that it is clear that
we support antimicrobial stewardship. We believe it is
important to use the right drug at the right time for the right
bug. And so, stewardship is important. And as a result,
antibiotics and antifungals are going to be used more sparingly
than you would see at typical products, especially in a
hospital setting.
However, the way reimbursement is set up in the hospital
with DRG, hospitals are incentivized to use cheaper or less
expensive medication than newer, more potentially costly
innovation.
What we would like to see is a reform to reimbursement so
that hospitals are not incentivized to put our new--newer
antibiotics on the shelf, in reserve, but to use them when it
is appropriate.
They need to do the right testing, of course. But when they
see that a bug is susceptible to a newer antibiotic or to a
newer antifungal, they shouldn't be prohibited from using that
because of cost.
At the end of the day, the cost of inaction, of not using
the right products sooner cost the health care system money,
and of course, it cost lives.
Senator Budd. Thank you for that. Again, thank you all. I
yield.
Senator Markey. Thank you, Senator.
Senator Hassan.
Senator Hassan. Well, thank you, Chairman Markey and
Ranking Member Marshall for this hearing. I just also want to
thank all the witnesses for your participation and testimony.
And Ms. Lawrence, I am especially grateful for your testimony.
It is hard to talk about personal experience in a large setting
like this, but it is really, really important, so thank you. I
want to start with a question to you, Ms. Miller.
You have just been having some of this discussion with
Senator Budd, but antibiotic resistance is obviously a serious
and emerging threat to global health, and we need to work
together to encourage the development of new products that can
treat infections that resist current antibiotics.
That is obviously the whole point of our discussion today.
What I am understanding is that many large drug companies used
to--sorry, used to develop antibiotics, but over the last
decade, this field has narrowed to a handful of small biotech
companies, right.
You have just been talking with Senator Budd about some of
the obstacles for investment here, but for these smaller
operations that are now driving the research, are there any
obstacles you haven't discussed to antibiotic innovation and
bringing new antimicrobial drugs to market?
Ms. Miller. Thank you. The crux of it is the commercial
marketplace problem. If there were to be a sound commercial
marketplace, then you would see larger companies and investors
willing to invest in the space. Because of the broken
marketplace, this is why you have only a few companies actually
doing development in the space.
Fortunately, we do have collaborations with BARDA and other
private, public partnerships that are helping and assisting,
but it is not enough. We need to fix reimbursement. We need to
have pull incentives that will help address the commercial
marketplace and make it possible for companies to be
sustainable in the space.
Senator Hassan. Well, thank you for that. One of the things
that I think we could do, in addition to pursuing Government
investments in boosting the demand for new antibiotics, is to
look at ways we could leverage the tax code to provide
incentives to startups so that they would engage in this kind
of innovative research.
I will continue to pursue that as well. Dr. Boucher, while
drug innovation is essential, bringing new anti-microbials to
market only addresses part of the problem. And Dr. Apley was
just discussing some of that with Senator Markey.
Doctors also need tools like testing capabilities and
advanced equipment that can mitigate the threat of drug
resistant infections. So outside of new drug development, can
you speak to other areas of innovation that are critical to
meeting the threat of drug resistant infections, such as
diagnostic tests and more advanced antimicrobial surfaces in
hospitals?
Dr. Boucher. Sure. Thank you, Senator Hassan. Absolutely.
So, this problem is a wicked problem, and it requires a multi-
pronged approach.
Infection prevention is vitally important, and that is
everything from washing our hands to making sure every
procedure that we do on a patient is done in the best way to
prevent as many infections as possible. Diagnostic testing,
which Dr. Apley raised, very important.
We are in a situation where we have the science that has
brought us incredible technology for diagnostic testing, but
there is this disconnect in both the way they are developed and
approved by the Food and Drug Administration, in the way they
are reimbursed by the Government and private payers and in
hospitals. That has been a barrier. Then I will come back to
the workforce.
In my role as a dean, I have the privilege to help educate
the workforce of tomorrow. And that is not just physicians, it
is all other health professionals. We need experts to do this
work.
You heard from Dr. Apley a little bit of how complicated it
is to actually choose the right drug for the right patient. We
need to be able to attract people to do this work so that our
children and their children will be protected.
Senator Hassan. Well, thank you for that. And that takes me
to my last question, which is to Dr. Apley. You have written
extensively about promoting the responsible use of antibiotics
in animals. How do we engage all providers in a broader
conversation to promote responsible, medically appropriate use
of antibiotics?
Dr. Apley. Thank you for that question. I will address from
the veterinary side what we are doing. We work through both
producer organizations and veterinary associations.
We have developed guidelines for our veterinarians to put
stewardship programs in action, and we spend a lot of time
starting right at the start with case definitions, diagnostics,
and applications, and then reasonable choices.
It is a combination effort between everyone on our side of
caring for animals, and the--we have had one whole meeting at
PACCARB that based on--was based on communication. And that
communication aspect and aiding in that communication is the
basics of all of it.
Senator Hassan. Well, thank you. And I will yield back and
may follow-up in terms with all of you about what resources and
guidance is useful to practitioners, and how we can make sure
they have the best information readily available. Thanks.
Senator Markey. Thank you.
Senator Marshall.
Senator Marshall. Right. Thank you, Mr. Chairman. Ms.
Lawrence, you are a living, breathing miracle. And we want you
to know that we want you to see your son graduate from high
school. We want to see you have grandchildren someday as well.
And I remember my first patient--with cystic fibrosis.
I mean, there was once upon a time no cystic fibrosis
patients would think about conceiving, and it was certainly
just an incredibly tough pregnancy if they did. So, in many
ways, the innovation is working because of these innovative
drugs as well. What is the doctor, your doctor says about your
future? What does your future look like?
Ms. Lawrence. Thank you for the question, Ranking Member
Marshall. There have been so many medical advances, especially
with the highly effective modulators, but they are not a cure
and they do not prevent infection. They have offered a level of
stability, which has been really nice----
Senator Marshall. Is that gene therapies, the modulators?
Ms. Lawrence. Not--the highly effective modulators as in
Trikafta, which I can explain more but it would take me a long
time.
Senator Marshall. That is Okay.
Ms. Lawrence. It stabilizes the experience. It stabilizes--
for many patients, it raises pulmonary function tests and
decreases infection. I have been in clinical trials for every
generation of these modulators, and it has made a big
difference, but it is not stopping me from getting infections.
That is my biggest threat. And also, like the infection
breeds pneumonia, breeds hemoptysis, and it is just this
vicious cycle. So that is my biggest threat by far. And if I
may, Ranking--Chairman Markey, I just wanted to add to my
answer to your question about new antibiotics.
There is also a timing factor. And while I have very good
access to health care and affordable insurance, in order for
them to cover a new antibiotic, they make it extremely hard,
and there are hoops that need to be jumped through and cultures
take days to come back, while my infection is rapidly like
progressing to pneumonia and other----
Senator Marshall. Is there like a prior authorization issue
that your doctors have to go through?
Ms. Lawrence. With some of the newer antibiotics, you have
to submit a culture. You have to prove that all the antibiotics
are resistant. You have to test it to see if you are--it is
this whole process that requires often in-patient hospital
stays. So, they definitely do not make it easy to access the
newer antibiotics.
Senator Marshall. Thank you. Dr. Boucher, I am going to get
a free medical consult from you here. Most of your patients you
see are probably people that survive organ transplants. That
they have--maybe they have taken cancer therapy recently and
then we lose them to an infection. What would the message of
hope you give to a cystic fibrosis patient like Ms. Lawrence?
What do you need to be successful so she can see her
grandchild?
Dr. Boucher. Yes, thank you for the question. It is a huge
privilege to take care of patients before and after
transplants, and after lifesaving chemotherapy, and with cystic
fibrosis.
What we physicians and all clinicians need is we need tools
in our toolbox, right. We need ways to prevent infection and we
need drugs to treat those infections, which still happen. So,
and it is not just one, as was pointed out earlier.
We need a pipeline that is robust and renewable because we
know resistance will march on. And so really finding a solution
to that. That is the idea of the subscription model as a way to
focus on value, not volume, of antibiotics, to use them well
through stewardship, but to have them be developed and
delivered to our patients in ways that are predictable and
reproducible so that those drugs that the Government invests in
will be on the shelf in my pharmacy when a patient has a life
threatening infection.
Not requiring a weeklong prior approval, but on the shelf,
in the pharmacy, in Boston for the patient.
Senator Marshall. Got it. Dr. Boucher, not many people have
watched somebody die. What is it like to watch your patients
die because you don't have the right antibiotic? It starts off
as a kidney infection, starts off with the pneumonia. What is
it like to watch them die and not have the antibiotic that you
need?
Dr. Boucher. Well, I will just start by saying I chose the
profession of infectious diseases 30 years ago to cure
patients, right. Antibiotics, as Senator Markey said at the
open, are curative, lifesaving drugs.
I came into this field to cure people of infections and
send them home to live their lives--to enjoy the transplant,
that precious gift that they get. So, coming to the point where
I have had the sad duty to sit with a lady who lived through
rounds of chemotherapy for her leukemia, who had an infection
for which we had no therapy, and to watch her go from sitting
in the chair to sicker and sicker and dead in a number of days,
is beyond heartbreaking.
It is a privilege to care for patients at that time in
their life, but it is absolutely heartbreaking and not the
reason that I went into medicine or so many others go into
medicine.
Senator Marshall. Thank you. Dr. Apley, speak a little bit
about what agriculture protein production that we have done to
decrease the use of antibiotics and to address these issues,
and specifically talk a little bit about how the 2017 law has
impacted your world.
Dr. Apley. Thank you, Senator Marshall. If you go back to
2017 and look at the FDA sales data for antibiotics following
that, and 2017 was the start of the transition to all medically
important antibiotics used in feed to the veterinary feed
directive, and any used in water to under veterinary control.
The next year we saw, for example, tetracycline use dropped
by around a third as the veterinarians took control of that and
had discussions with their clients based on the stewardship
principles.
The last time a new antibiotic group was approved that we
use in food animals was 1978, that a new group was approved.
So, we are using tried and true older compound groups. We get
new members of them. Also, if you look at our veterinary
organizations, we ascribe to the AVMA stewardship definition
and the ways we go through to look at those.
The other thing that just happened July 1 of 2023 was that
all of our antimicrobials now that were previously over the
counter have gone under veterinary control. So, veterinarians
are involved in all decisions.
We have some very frank and candid discussions about what
we should and shouldn't be doing and how we address the issues
of prevention control, animal movement, etcetera, biosecurity
to decrease the need.
Senator Marshall. That is great. And by the way, we have
some agriculture initiatives with food supplements, feed
supplements that would also decrease a lot of those bacteria as
well. Ms. Miller, I am going to finish up with you, several
questions here as well. Big picture, how many failures does
your company have before they get a--get one across the finish
line?
Ms. Miller. Well, I mean, in this space, you probably have
a 1 percent chance of getting a product from initial idea of
conception to approval. It is a pretty high failure rate when
it comes to development and a pretty costly one.
Senator Marshall. Yes. When--I used to help run a hospital
and you try to keep your formulary tight from a cost management
standpoint. And some of the antibiotics that you would make
maybe only be used 5, 10, 20 times a year as well, and there is
no way that my hospital could afford to keep that in stock.
We think about the DRG reimbursement. So, we would--if a
patient is admitted for pneumonia, we are going to get a lump
sum of money, whether we use ampicillin or a cephalosporin, or
maybe your miracle drug as well. So, a basic DRG, and I know
there is exceptions to that.
Can you just kind of walk us through what your solution
would look like for that type of patient that probably is going
to be resistant. They have got COPD and they have been in the
ICU for 3 days already.
They are not getting better. It is drug resistant
antibiotic. What would the solution be look like from a
reimbursement model?
Ms. Miller. Well, I think it is important to look at the
big picture. So, yes, there is a DRG, and I do believe that we
need to reform reimbursement. We can look at using NTAP as an
example. That is already a framework in place, and we can make
reforms to it so that antimicrobials are better suited for use
in the NTAP construct.
However, we have to look at what does it cost to have that
patient hospitalized for extended period of time. I can tell
you that every day a patient is in a hospital not getting the
care that they need, further deteriorating, costs the hospital
and costs health care much more than it would be----
Senator Marshall. Probably $5,000 or $10,000 a day,
literally----
Ms. Miller. Exactly. We have to really consider that the
products that we have developed, that we have made available,
or we are making available to patients, are curative, right.
This is invaluable.
Senator Marshall. Right. I appreciate the answer and be
respectful. I need to move on. I do appreciate everybody coming
to--your testimoneys. I need to go to another hearing. I would
like to come back, and circle back about how do hospital share
that particular drug.
Not all small hospitals could keep every one of those in
stock, but how do we better share those as well, and so that
Tufts can get it tomorrow, but also Great Ben Regional Hospital
can get it tomorrow as well. So, thank you so much, Chairman.
Ms. Miller. Thank you.
Senator Markey. Thank you, Senator Marshall. And again,
thank you for your partnership on this issue.
Senator Hickenlooper.
Senator Hickenlooper. Thank you, Mr. Chairman. Thank all of
you for your time. I still--I was trying to come up the stairs.
I still barely have caught my breath coming up the four floors
here. Obviously, microbiologically weakened somehow. On a more
serious note, I first learned--I learned firsthand the
importance of what we are talking about today.
My father passed away in 1960 after a long battle with
colorectal cancer. But a big part of his challenge was the fact
that they pretty much only had penicillin in those days, and
after a couple of years, several operations, he would get
infections that they were unable to treat.
My mother would tell stories about waking up in the middle
of the night several times and having to--he would have had
cold sweats and she would have to roll him over and get clean
sheet under him, then roll him back on a clean sheet, get the
rest of the sheet put down, and what a trial that was for him
every night.
It is amazing that we have come so far and yet we still
haven't progressed as far further as one would hope in this
issue. So, I will start with Dr. Boucher. The development of
new antimicrobial drugs hasn't kept pace with the increasing
rate with--these pathogens become drug resistant.
Obviously in large part due to the fact that there is not
much financial incentive, as we are hearing discussed today, to
innovate in this drug space. We have co-sponsored the PASTEUR
Act, which you referred to, which would allow the Federal
Government to enter into subscription contracts with critical
need antimicrobials.
Dr. Boucher, how would the subscription mechanism embedded
in the PASTEUR Act incentivize the development of new
antimicrobials?
Dr. Boucher. Thank you very much for your question,
Senator, and for your support of the PASTEUR Act. The PASTEUR
Act uniquely values antibiotics for their value, not for their
use. So, it delinks any incentive to overuse antibiotics, and
it focuses on the most needed antibiotics for the most
resistant infections.
There are clear criteria the developer needs to meet to get
this benefit of this subscription reimbursement, guaranteed
reimbursement, and it is linked to stewardship, which is very,
very important to ensure that we clinicians use the antibiotics
in the best way possible so that they are preserved for as long
as possible.
This is felt to be a much needed first step in getting us
back to a healthy economic framework for antibiotics. And I
just wanted to come back to the comment about CARB-X that was
made earlier. CARB-X is probably the most successful public,
private partnership with BARDA and many other agencies.
To date, CARB-X has over a dozen products in clinical
trials--that is in patients. And if we don't see progress in
something like the PASTEUR Act, all that investment will go to
waste, and those medicines won't get to our patients. So
really, really important, and thank you so much for your
support.
Senator Hickenlooper. Of course. And thank you for all your
work. Ms. Miller, a lot of the drug research and development is
obviously, as has been discussed by all of you, hard work and
doesn't often have many victories.
Many of the skilled professionals behind this research the
creators of these innovations, are often lured away from the
uncertain antimicrobial drug market for more commercially
viable pursuits. The PASTEUR Act is designed specifically to
help reduce some of that uncertainty and to improve the
viability of the market.
In your opinion, how would the stability of the PASTEUR Act
help support recruitment and retention, not just recruitment,
but retention of the workforce we need to develop these drugs?
Ms. Miller. Thank you, Senator, for the question.
Absolutely, there has been a brain drain, we call it, in the ID
space. You have talent within the industry who really have
concerns about how much there has been an underinvestment in
antimicrobials.
People have left and gone to other pursuits like oncology
and other chronic diseases where the marketplace is more
certain. What PASTEUR does and novel pull incentives, it
creates the possibility of stability in the marketplace.
Knowing that there would be a sustainable marketplace would
then help bring people back into the space, not just people
from a development point of view, but investors as well.
Senator Hickenlooper. Right. And I see I am out of time
already. That is impossible, but anyway, I will try to get
back. If I don't, I will make sure that my additional questions
get entered into--you all get a chance to see them and respond
in writing. Thank you all again for your great public service.
Senator Markey. Thank you, Senator.
Senator Braun.
Senator Braun. Thank you, Mr. Chairman. It is an
interesting discussion because it looks like we are up against
a foe that so easily out maneuvers us. The more you use
something that is effective, temporarily, the more you are
giving it the chance to change and require something different.
I got interested in this, and it is I think called a
spirochete instead of a bacterium, but it was something that we
didn't know much about at all--tick borne diseases. And then
you find out that it is an old drug called doxycycline, that is
the only thing that can knock them out. And I guess what I am
wondering is, are we in a never ending battle of where we can
never get ahead of this?
When you are saying only 1 percent of any investment in
something to waylay any new malady hits paydirt, where does
this dynamic end? Because it looks like the dynamic generally
favors the micro-organism.
My question would be, start with Dr. Boucher, what is the
most recent example where there has been something so bad, so
widespread, where a current antibiotic wasn't working? How long
did it take to marshal the resources when you knew that you
needed to, to actually get something to the marketplace that
was going to work?
Dr. Boucher. Thank you for your question, Senator Braun. I
think we have to look at the example of COVID, right. It is a
virus, not a bacteria, but we marshaled--we marshaled, right,
and got a vaccine into arms in less than a year, right, and
drugs into patients very quickly, remdesivir, etcetera.
We can do this, right. The science exists. There are
numbers of candidates, drugs, the vaccines, diagnostics that
have advanced scientifically. There is no dearth of science.
The issue is really this economic problem and solving that at
the same time as we enact the multi-pronged approach of
prevention, surveillance, good diagnostic tests, all the other
things that are required to combat this wicked problem, but we
live in a country where technology is advanced.
We transplant every day. Heart transplant is normal--at
normal business in a hospital today----
Senator Braun. We did that in the matter of--because a lot
of that research was kind of building toward it, and it finally
got applied. What would you say if that urgency is there,
because sooner or later it will be either another virus or a
bacterium or even like a spirochete currently where we have so
many more diseases that are out there, tick borne that we
didn't know about.
Thank goodness, doxycycline, very inexpensive, still works.
So, what would you say when it comes to an antibiotic, not an
antiviral, unless they are completely analogous in terms of how
you would get there. Was there anything recently when it has
come to something that had to have an antibiotic and how long
did it take?
Dr. Boucher. Yes, I guess I would say, if we look at the
most recent antibiotic approvals, go back and drill back to
them, that was approved for Acinetobacter infections, that is
less than 10 years.
That was--that is an infection that we know is coming. It
is multi-drug resistant. So, this is a game where there needs
to be planning in advance for the threats we know and some we
don't know. Someone mentioned candida infections earlier.
Candida auris was not on the CDC threat list in 2015. It is in
2019.
Senator Braun. Is it one of the biggest concerns right
now--?
Dr. Boucher. It is a big concern.
Senator Braun. Yes.
Dr. Boucher. We need infrastructure, and we need something
like the PASTEUR Act. I think that is the one thing that you
all can do is to advance that bipartisan----
Senator Braun. That we are not doing it ad hoc based upon
the very urgent need. Someday that may not be quick enough.
Dr. Boucher. Correct.
Senator Braun. Ms. Miller, would you want to weigh in?
Ms. Miller. Well, we--so definitely there is a cost to
inaction, and we do need to be planful, we do need to prepare.
There is great science out there. It is just waiting to have a
stable home to land in.
If there is one thing that I would ask that be done today
is we need to reform the commercial marketplace. We need
reforms to reimbursement. We need pull incentives. We need to
fix the commercial marketplace.
Senator Braun. Anybody else want to weigh in quickly?
Dr. Boucher. I will just add one thing, that the PACCARB
released a report in March, linking pandemic preparedness to
AMR, right. This is not if, it is when, and this report goes
through all the different aspects that need to be addressed,
including the PASTEUR Act.
Senator Braun. Thank you.
Senator Markey. Thank you, Senator.
Senator Smith.
Senator Smith. Thank you, Mr. Chairman. Thanks for this
hearing. I don't know if everyone in this room knows this, but
today is Senator Markey's birthday, I believe. I could not miss
this opportunity to embarrass you in front of the whole
Committee staff.
Senator Markey. You have been very successful.
[Laughter.]
Senator Smith. It is always dangerous to go against your
Committee, your Subcommittee Chairman, your Committee Chair
like this, but happy birthday Ed.
Senator Markey. Thank you.
Senator Smith. I really appreciate all of you, and I
appreciate very much this hearing. And I am getting clearly
this--the broad message of this hearing, which is that we need
to take a comprehensive and holistic approach.
We need to improve access to education about infection
prevention measures like vaccines and handwashing. We need to
make sure that we are using antimicrobials responsibly, whether
it is in the hospital or in agriculture or in veterinary
medicine.
We need to be investing in the development and
manufacturing of new antibiotics in a market that isn't broken,
in a market that is really fix, that is working well. And so, I
want to dive into this from the perspective of shortages in
antibiotics and what we have seen with this issue, and whether
or not this question of a supply chain is part of the broken
part of the market. We saw shortages of antibiotics in this
last year.
We know that this is about, sometimes it is the antibiotic
itself or sometimes it is the component of the drug that we
don't have. And it was with this in mind that caused me to team
up with Senator Cassidy on our now bill, now law, the Onshoring
Essential Antibiotics Act, which basically helps to expand--the
concept is to expand domestic manufacturing capabilities by
allowing HHS to award grants to antibiotics manufacturers to
build or upgrade facilities here in the U.S. to basically
onshore our supply chain.
Let me start, Dr. Boucher, could you just talk a little bit
about how you see this shortage affecting patients and your
view of this?
Dr. Boucher. Thank you, Senator Smith, for the question. We
have seen antibiotic shortages for some years, and we see them
almost routinely. Our hospital pharmacists, send a thing out
every week telling us about shortages, and we manage them often
creatively thinking about substitutions and ways to manage.
But sometimes it is not easy and sometimes it does affect
patients. I am in a very fortunate position to have expert
pharmacists who work with me and supply chain experts. In rural
hospitals, in critical access hospitals, it is not so easy, and
the impact is greater.
Addressing this is a huge need, and thank you for your
attention. I will mention that especially injectable
antibiotics require very special kinds of manufacturing, often,
which is difficult.
This is part of the reason we need a more robust pipeline,
and we need to think about things like oral antibiotics. We
haven't had a new oral antibiotic in over a decade.
Senator Smith. Well, I think one of the things that we
learned from the pandemic is the threats that we have when we
do not have onshored manufacturing of so many things, including
antibiotics.
Maybe, I am wondering, Ms. Lawrence, if you would like to
comment from your own personal experience whether you have seen
issues with not being able to get access to an antibiotic that
you really needed because it just wasn't available? Not about
price, it is about availability.
Ms. Lawrence. Yes, thank you for the question, Senator
Smith. I have been impacted by antibiotics shortages and other
medical or medicinal shortages as well. And I am extremely
fortunate to have an amazing care team at Boston Children's
Hospital that knows how to work, pull, navigate.
I also happen to have a best friend who is a pharmacy
manager and can help with the pharmacy side. But I am very
lucky to have that, and if I didn't have that, if I were
elderly and didn't know how to navigate the system, or if I
didn't have the connections that I have, I would not know even
where to begin to work around that shortage.
Senator Smith. Yes, thank you for that. I think that is
really important. And you both are making the comment about how
antibiotic shortages affect different people differently based
on who they are, where they live. I just have a few more
minutes.
Dr. Apley, I wanted to ask you about the concept of One
Health, and the idea that human health and animal health are
inextricably linked and that too often our Federal agencies
that oversee these--oversee this sort of work in their silos,
rather than thinking about how we need to be thinking, again,
holistically and comprehensively about bugs.
I am wondering if you could talk a bit about this concept,
what you see around the One Health framework. Senator Young and
I worked on this together, and we have been working hard with
the Department of Agriculture in particular to get this One
Health framework adopted. Could you just talk a bit about where
you see this going?
Dr. Apley. Again, going back to experiences on PACCARB,
that was one of the fundamental underlying things, is we are
all in this together. If you look at the list of the American
Veterinary Medical Association's important resistant organisms
in veterinary medicine, and you look at the CDC's list in human
medicine, you will see pseudomonas staph aureus, nontyphoidal
salmonella listed in both.
We share a lot of organisms that we have challenges with,
and we also share a lot of the same needs for diagnostics, for
helping get the best information to our practitioners together,
understanding our human behavior and its interaction with how
we dispense, and so many of the same messages, so many--so much
of the same information is vital to both physicians and
veterinarians that it is absolutely wrapped up together.
Senator Smith. Thank you. I know I am out of time, Mr.
Chairman. I appreciate this hearing very much.
Senator Markey. You can have extra time for wishing me a
happy birthday. Thank you so much, Senator Smith. Let me ask
you, Ms. Lawrence, your disease is one that actually has had
enormous progress because of what the families have done. My
friend who I went to Malden Catholic High School with, Joe
O'Donnell, his boy Joey contracted cystic fibrosis and there
was no cure.
Companies really weren't doing the research on it. So, he
along with the families each year raised money and then said to
biotech companies, if you do research in cystic fibrosis, we
will give you our money to do the research. And ultimately, the
families raised hundreds of millions of dollars in order to
incentivize research. And that is where a company named Vertex
got their funding. It was from the families, to give them that
incentive.
These breakthroughs have all come because of that
incredible entrepreneurial activity. My friend ultimately wound
up, Joe O'Donnell, going to Harvard Business School. So, we use
that model to incentivize the private sector to move. And Joey,
little Joey would be your age today, but he passed away at a
very, very young age.
But now life expectancy has been lengthened dramatically.
So, we know that it can happen. We know that the breakthroughs
are there. And we just have to find the methodologies that
ensure that we are going to have research, be medicine's field
of dreams from which we harvest the findings to give hope to
families that they won't suffer unnecessarily from diseases in
their family's lives.
How, Ms. Lawrence, can we better support patients in
response to anti-microbial resistance?
Ms. Lawrence. Thank you for the question, Chairman Markey,
and happy birthday as well. I actually met Joe last July at a
conference and he is wonderful, and he has done so much for the
community, as has the Cystic Fibrosis Foundation.
I work with them on several levels, and I think that they
are--one thing that they really do well to drive community
incentive in working together and funding different things is
that they have a patient centered model of care. So, they hear
the patient voice. They take into account the community needs
and where the lack is, and that better directs the science.
They have like patients like myself have input at a
research level, at a grant level, at a need--like at a workshop
level. At every level of the process, the patient voice is
front and center, and that has really driven where the money
goes and progress.
Senator Markey. Beautiful. Thank you. Dr. Boucher, in your
written testimony, you talked about how climate change
facilitates the risk of anti-microbial resistance. Can you talk
more about that?
Dr. Boucher. Thank you, Senator Markey, for the question.
We know that climate change leads to more antimicrobial
resistant infections through a number of ways. One is through
wound infections in warmer temperatures often are infected with
antimicrobial resistance organisms.
Waterborne organisms travel more, and we see more
antimicrobial resistance there. And a lot of pathogens are
picked up from the soil that has more resistant organisms in
warm and hot climates.
We are already seeing the impacts and we are doing studies
in the Tuft Center looking at wastewater to see--and we are
seeing changes already with just the small incremental changes
in temperature we have seen.
Certainly, very linked, and linked in a one health way,
right, from humans, animals, and the environment, as we see
climate change evolve.
Senator Markey. As temperatures warm, insects, animals now
migrate to other parts of the planet that otherwise they would
never have moved. And then that causes disease to migrate in
ways that perhaps those populations are not as protected
against.
Dr. Boucher. Absolutely. We see migration of vectors of
illness, things like animals, and we see evolution in places
where infection isn't recognized because people haven't put two
and two together that the area is moving. For example, moving
South like we have seen with Lyme disease, something very
endemic in Massachusetts, which has now moved way South in our
Country.
Lots of change, lots of room to act in the positive as
well. And truly back to the wicked problem, one of the
multipronged approaches needs to be really thinking about
climate active impacts on AMR.
Senator Markey. Again, wicked is such a Massachusetts,
Boston word as well, so it is bad. So, Dr. Apley, you are an
advocate of the one health perspective. Could you explain the
One Health approach and how our environment affects the
people's health in the context of antimicrobial resistance?
Dr. Apley. I think we have been able to identify common
approaches that by supporting them we advance stewardship and
our antibiotic decisions across every place we use them. One of
the things that has happened in the PACCARB, again, was as we
start to look at issues of fungi, we have brought in someone on
that committee--that counsel, excuse me, that is an expert in
agricultural applications of antimicrobials.
We realized that this One Health really does involve the
environment and any place we might be using the antimicrobials.
And again, it involves diagnostics, preventives, new and novel
ways of preventing disease and dampening it down.
Once you break down the silo, just personally from seven
and a half years on PACCARB, the things I learned from the
human side that I take the veterinary medicine, and I think
maybe that went the other way too, that having a group that is
just really focused on breaking down those silos is incredibly
important.
Senator Markey. Thank you. Ms. Miller, you are the chair of
the Antimicrobials Working Group, the pharmaceutical and
medical device industries coalition on this issue.
According to the Government Accountability Office, the
existing development of new drugs that could treat bacteria
currently resistant to medications is insufficient.
Ms. Miller, how are companies partnering with the Federal
Government to incentivize drug development with FDA pathways
and exclusivity periods, and is that partnership working?
Ms. Miller. Thank you for the question. Happy birthday. So
there are really good and productive public, private
partnerships to support AMR. It isn't enough in the end, right,
because we need to make sure that we are continually innovating
because the bugs are continually evolving.
We need to ensure that we have an ongoing stream of
innovation to have newer, safer antimicrobials over time. But
existing relationships, they are working though, right, and we
need to continue that.
At the crux of it, though, we do need to address the
commercial marketplace because I believe that if we do that, we
will create an incentive for companies and for investors to
come back into the space to do more development and to ensure
that the relationships that we do have, the partnerships that
we do have, these products can actually land in the marketplace
effectively.
Senator Markey. Again, let's talk about that. The families
with cystic fibrosis, I think there were only 35,000 in
America, they saw a market inefficiency. They saw where the
private sector was not going to respond.
They injected themselves into it, raised the money, said to
a number of companies, you do the research we will help to fund
you, and ultimately Vertex emerged out of those companies as
the one that was doing the best work. So that was a market
inefficiency. Just too few people are affected.
What do we have to do, Dr. Boucher, in order to deal with
this issue that such a small number of people potentially
benefit from it, but by benefiting from it, they also stop the
spread of it, potentially.
Dr. Boucher. Senator Markey, happy birthday. I don't want
to forget. And thanks for the question. So, you hit on one of
the key really important criteria for antibiotics, right. The
use in one patient affects the whole community. So that is the
way we should care, even if this particular infection only
impacts a few.
I am going to come to something that we haven't talked
about explicitly that I think is really important, and that is
awareness. So, it is a sad reality that in 2023 we still have
an awareness problem for this AMR in our Country. And holding
this hearing is a good step in that, and that is what many of
us at this table spend our time trying to do. But we have to do
better, right.
We still lack a clear voice and a clear patient voice. The
National Action Plan has called for a Federal champion for AMR.
In the UK, you might have seen Dame Sally Davies. She is the
champion of AMR. She is now a U.N. Ambassador. She has done
more for this in the world. She is leading and I think we need
that in our Country.
I hear you loud and clear. We are doing more clinical
trials with patients at the table. As we develop the questions
and trials through the NIH and Antibacterial Resistance
Leadership Group, we are making progress on looking at quality
of life. Lots more to do and lots more rallying from the base
in terms of patients and families.
Senator Markey. Talk a little bit more about the champion.
Who is that person and what are they doing?
Dr. Boucher. The champion that I have seen is this--Dame
Sally is the spokesperson in Europe and globally now for this
problem. So, across the Government, across the globe, actually
speaking for the different stakeholders and bringing very
practical things to the table with one voice and really being
recognized.
We at PACCARB recognized this back in 2015, 2016, and it
was incorporated into the National Action Plan, it just hasn't
been implemented. But I think appointing such an individual
would help advance this problem and our response to it.
Senator Markey. You are saying that the Administration
should appoint, name a champion.
Dr. Boucher. Yes, the ask is the President----
Senator Markey. A person has a spotlight to continue to
keep this issue front and center.
Dr. Boucher. Yes, sir. That is the ask.
Senator Markey. Okay. We will try to help you to accomplish
that goal. I think that is a great idea. And we need to have
somebody who is in charge to be applying the pressure that all
of the families in our Country feel on this issue.
Let's do this, let's--and thank you all, by the way, so
much for this incredible hearing today. I think you are really
advancing the cause, and you can see the enormous interest
which the Subcommittee has in this subject.
Let's do this, let's give each one of you 1 minute to
summarize what you want the Subcommittee to retain from your
testimony today. Just to--and we will go in reverse order of
the original testimony so that you can give us your summary to
the jury, to the Subcommittee in terms of what our agenda
should be. What should we remember from today's hearing? So, we
will begin with you, Ms. Miller.
Ms. Miller. Thank you. And maybe what I will also start by
saying is that while AMR is an issue where sometimes we only
have antibiotics or antifungals to address a few patients, what
we do know is that there are a number of patients that are
affected by AMR every day. They are dying from infections.
They may have cancer and maybe their loved one thinks that
they are dying from cancer, but they actually die from an
infection. And so, this is an everyday person's problem. It is
not something that is in the future to be a problem for our
families and our loved ones. It is a today problem for folks.
What I would definitely like for everyone to walk away from
today's discussion is to really understand that AMR is a threat
to us, to our society, to our medical and health care system.
That we need to have adequate development and ongoing
innovation in this space to ensure that we will be able to save
patients' lives. We also need to address the commercial
marketplace.
This is definitely something that really needs the Federal
Government to step in and address. We need to see reforms in
reimbursement. We need to see pull incentives like the PASTEUR
Act be put in place so that all of the development, all the
public, private partnerships that are happening today actually
have a place to land and that patients can get the lifesaving
medicines that they need.
Senator Markey. Thank you. Ms. Lawrence.
Ms. Lawrence. I hope that I have given a human depiction of
what antibiotic resistance looks like so that it becomes more
relatable to most. And I hope that I brought a sense of
humanity to the issue that it is not, many of us are not as
impacted by something until it happens to us, and until we are
personally affected by it.
I hope that I can shed some light or that the Committee
takes away, this is a global problem that will affect you at
some point in time. So how proactive do you want to be? And I
second the PASTEUR Act before this Congress as well.
Senator Markey. Thank you. And thank you for your powerful
testimony here today. You were invaluable in putting the human
face on this crisis.
Dr. Boucher.
Dr. Boucher. Thank you, Senator Markey. I echo the
gratitude for being here and emphasizing that this problem is
here and now, affects all of us, and we need to act
immediately.
We need to ensure that we have a workforce to prepare for
and address this problem, and we need to advance the PASTEUR
Act, the bipartisan act supported by the IDSA and over 200
organizations that will provide a subscription model for the
most needed antibiotics and is linked to good stewardship and
the prudent use of those antibiotics. Thank you.
Senator Markey. Thank you, doctor.
Dr. Apley.
Dr. Apley. Thank you, Chairman Markey. Two things. I want
to be very clear that new antibiotics are very, very important.
But as a clinical pharmacologist, I also see a need for
advancing our understanding of the regimens we use for existing
antimicrobials. I think that could be a very big thing we could
support.
No. 2, one of the words we really haven't used here today
is risk. And when a physician or a veterinarian takes a stand
on antimicrobial stewardship and saying, I know you want one,
but we are not going to, there is a risk that is undertaking,
and supporting physicians and veterinarians in undertaking that
risk with information and collaboration is incredibly
important.
Senator Markey. Okay. Thank you, Dr. Apley, very much. And
we thank everyone who has participated today, especially our
witnesses who have traveled here today from Massachusetts,
Kansas, and New York.
Each witness here told us loud and clear, if we do not
address antimicrobial resistance, we will face a growing health
care threat to our Country. And today, we are not only
illustrating the problem, but illuminating the path forward. We
need a health care system that puts people first, providers to
have all the tools readily available to treat patients with the
best medications available.
We need to find a way in which we incentivize the
development of new solutions to this problem, and we need a
healthy planet that doesn't facilitate the spread of these
deadly diseases.
Ordinarily, at this point, I would ask unanimous consent to
revise and extend my remarks or the remarks of the Committee
Members here. But in this instance, I am going to ask to revise
and delete any references to my birthday from the record.
[Laughter.]
Senator Markey. Without objection. And I ask unanimous
consent to have a statement from stakeholders outlining
priorities for addressing antimicrobial resistance.
[The following information can be found on page 50 in
Additional Material:]
Senator Markey. For any Senators who wish to ask additional
questions for the record, it will be open for 10 business days
until July 25th at 5.00 p.m., and all Senators are invited to
ask those questions in writing, and for the witnesses then to
answer them in writing as well.
With that, this very important hearing is adjourned. Thank
you.
------
ADDITIONAL MATERIAL
Healthcare Leadership Council,
July 11, 2023.
Hon. Ed Markey Chairman,
Hon. Roger Marshall, MD, Ranking Member,
Senate Committee on Health, Education, Labor, and Pensions,
Subcommittee on Primary Health and Retirement Security,
Washington, DC.
Dear Chairman Markey and Ranking Member Marshall:
The Healthcare Leadership Council (HLC) appreciates the opportunity
to provide comments in advance of your hearing, ``Superbugs: The Impact
of Antimicrobial Resistance on Modern Medicine.''
HLC is a coalition of chief executives from all disciplines within
American healthcare. It is the exclusive forum for the Nation's
healthcare leaders to jointly develop policies, plans, and programs to
achieve their vision of a 21st century healthcare system that makes
affordable high-quality care accessible to all Americans. Members of
HLC--hospitals, academic health centers, health plans, pharmaceutical
companies, medical device manufacturers, laboratories, biotech firms,
health product distributors, post-acute care providers, homecare
providers, group purchasing organizations, and information technology
companies--advocate for measures to increase the quality and efficiency
of healthcare through a patient-centered approach. We are uniquely
positioned to address innovation comprehensively from all perspectives
in the healthcare industry.
HLC thanks you for focusing on the critical issue of antimicrobial
resistance (AMR) and urges Congress to enact S. 1355/H.R. 2940, the
``Pioneering Antimicrobial Subscriptions to End Upsurging Resistance
(PASTEUR) Act of 2023,'' as an important step in this effort.
AMR poses a serious threat in the U.S. and around the world. AMR is
the leading cause of death globally. It is estimated to have directly
caused at least 1.27 million death and contributed to another 5 million
deaths in 2019. \1\ In the U.S., more than 2.8 million antimicrobial-
resistant infections occur and are responsible for more than 35,000
deaths each year. \2\ Because emergencies often exacerbate the AMR
crisis, measures to address AMR should be incorporated into broader
emergency preparedness efforts. For example, the COVID-19 pandemic
caused a surge in hospitalizations and ventilator use. As a result,
U.S. hospitals experienced a 15 percent increase in AMR infections and
deaths in 2020. \3\ Hurricanes and other natural disasters also
increase the spread of infections. AMR should also be considered in
bioterror preparedness, as agents used by bioterrorists may be
genetically engineered to resist current therapeutic antimicrobials.
---------------------------------------------------------------------------
\1\ Global Burden of Bacterial Antimicrobial Resistance in 2019: A
Systematic Analysis, The Lancet, (January 19, 2022), https://
www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-90/
fulltext.
\2\ National Infection & Death Estimates for Antimicrobial
Resistance, Centers for Disease Control and Prevention (December 13,
2021), https://www.cdc.gov/drugresistance/national-estimates.html.
\3\ COVID-19, U.S. Impact on Antimicrobial Resistance, Centers for
Disease Control and Prevention, (2022), https://www.cdc.gov/
drugresistance/pdf/covid19-impact-report-508.pdf.
Despite tremendous need, there is still a lack of progress in the
development of critical new antibacterial therapies to tackle the
threat of AMR. Of the 12 antibiotics that have been approved since
2017, 10 belong to existing classes with established mechanisms of AMR.
In 2021, the World Health Organization (WHO) reported only 27 new
antibiotics in clinical development against priority pathogens, down
from 31 products in 2017. Of the 27, only six products meet at least
one of the WHO's criteria for innovation--which include absence of
known cross-resistance, new target, new mode of action, and/or new
class--and only two acts against critical gram-negative bacterial
pathogens, which are multidrug-resistant and have few other treatment
options. \4\
---------------------------------------------------------------------------
\4\ 2021 Antibacterial Agents in Clinical and Preclinical
Development: An Overview and Analysis, The World Health Organization,
(May 27, 2022), https://www.who.int/publications/i/item/9789240047655.
This stagnant innovation not only fails to meet the serious current
threats AMR poses, but we can expect the consequences to modern
healthcare to continue to grow in the future if no action is taken. It
is important that new incentives, including post-market incentives, are
put in place to help provide the economic certainty needed to bring
these critical medicines to the market. HLC supports the innovative
subscription model proposed in the PASTEUR Act. Payment modes based on
volume only exacerbate the risks of AMR, as over-usage of antibiotics
is a major driver of resistance. Under the PASTEUR Act, the Federal
Government can enter into contracts with innovators to pay for a
reliable supply of novel antimicrobials with payments that are
---------------------------------------------------------------------------
decoupled from the volume of antimicrobials used.
This delinked approach is similar to Project Bioshield, which
provides multi-year funding to support procurement of medical
countermeasures (MCM) for national security. Like MCM, antimicrobials
have a very limited commercial market. The PASTEUR Act will provide
antimicrobial innovators with a more predictable return on investment
necessary to revitalize the antimicrobial pipeline.
Thank you for your efforts to address the AMR crisis. HLC looks
forward to working with you on our shared priorities. If you have any
questions, please do not hesitate to contact Debbie Witchey.
Sincerely,
Mary R. Grealy,
President.
______
[Whereupon, at 11:39 p.m., the hearing was adjourned.]
[all]