[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

                               __________

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                                Pensions
                                
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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/.
---------------------------------------------------------------------------
                    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.
---------------------------------------------------------------------------
    \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.

---------------------------------------------------------------------------
            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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \29\  https://www.cidrap.umn.edu/antimicrobial-stewardship/
clinicians-describe-challenge-treating-multidrug-resistant-war-wounds.
---------------------------------------------------------------------------
                  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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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 
---------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
    \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.
---------------------------------------------------------------------------
    \41\  https://www.medscape.com/slideshow/2022-compensation-
overview-6015043?icd=login-success-email-match-norm.
---------------------------------------------------------------------------
                               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\
---------------------------------------------------------------------------
    \42\  https://www.hhs.gov/sites/default/files/paccarb-pandemic-
preparedness-report.pdf.
---------------------------------------------------------------------------
     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.
---------------------------------------------------------------------------
    \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\
---------------------------------------------------------------------------
    \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]