- 6 days ago
We’ve Reached "The End of Antibiotics... Period" - Says associate director at Centers for Disease Control
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00:15Tonight, we are seeing now the emergence globally of some forms of bacteria that are effectively
00:21untreatable.
00:22Each year, at least two million people are infected with drug-resistant superbugs.
00:27They had asked me to sign the papers to let her go, and I did.
00:31And at least 23,000 die from them.
00:33He had some bugs that they had never seen before.
00:37We immediately went on high alert, the equivalent of DEFCON 5.
00:41No matter what we did, the bacteria was still spreading.
00:44Frontline continues its reporting on how we got here.
00:47In overusing these antibiotics, we have set ourselves up for the scenario that we find ourselves in now.
00:54We're running out of antibiotics.
00:55The newest threats.
00:57Where did it come from?
00:58We don't know exactly where this bacteria came from.
01:01The economic realities.
01:03There is an increasing recognition that antibiotics are not a good thing to run off a pure capitalistic market.
01:11And what happens now?
01:12A lot of what we're doing requires resources.
01:15If there is less money, there are tough choices that have to be made.
01:18It could happen to your next-door neighbor.
01:20It could happen to your child.
01:21It could happen to anybody.
01:23Those bacteria are out there.
01:25Tonight on Frontline, hunting the nightmare bacteria.
01:52This is the story of three seemingly disconnected events beginning at the same time.
01:59What they each have in common is a type of infection that is becoming impossible to treat.
02:06A type of infection that has triggered deadly outbreaks, even at one of our most prestigious hospitals.
02:13It is a crisis that is spreading alarmingly fast, threatening everyone, even the healthy.
02:28Our first story starts in Tucson, Arizona, in May 2011.
02:35When I think about that time, I think about spring and just how busy it was and how beautiful she
02:47was.
02:50She was 11 and a half years old and just physically perfect, beautiful from head to toe.
02:57Slim, you know, white, blonde hair from being out in the sun.
03:03A little bit of freckles across her nose, a little bit of freckles across her nose, bright blue eyes, paying
03:08attention to what her clothes looked like and her hair.
03:11Never stopped talking. Talked a mile a minute.
03:15That was Addie at that just, you know, in the month before she got sick.
03:23Journalist David Hoffman started reporting on the threat of superbugs for Frontline more than four years ago.
03:29There's a warning from the CDC.
03:31New and extremely dangerous.
03:33Superbug.
03:33Covering what government officials have called a nightmare.
03:36It's a deadly nightmare bacteria.
03:38Even the CDC has called it a nightmare.
03:41A kind of dangerous bacteria that is increasingly resistant to the strongest antibiotics.
03:47Morning.
03:47Hi, I'm David Hoffman.
03:48That's what brought us to Tucson, Arizona, in 2013, to find out what happened to Addie Raricic after she complained
03:55to her mother about a pain in her hip.
04:00I thought, well, you know, she's just finishing up softball.
04:04She had been to the track meet, you know, it all kind of, well, it could have been an injury.
04:10I gave her some ibuprofen.
04:12As the night wore on, her pain got worse.
04:15She didn't sleep much that night.
04:17Woke me up a couple of times asking if she could take a hot bath or have another ibuprofen.
04:24The next day, Tanya Raricic, a nurse for 16 years, took Addie to a local hospital where they said she
04:31had symptoms of a virus.
04:34But over the next few days, the pain spread and the fever got worse.
04:40I was afraid.
04:41At that point, I remember being very afraid.
04:44And so I packed a bag and we went to another hospital that had specialized in children's care.
04:53I remember thinking, she looks bad.
04:57This is bad.
04:58Something's really, really wrong.
05:01They put her on antibiotics.
05:03They were, her blood pressure was dropping.
05:05They, you know, were making space in the ICU for her.
05:11The next morning, she needed oxygen via mask.
05:16They looked at part of her lungs and diagnosed her with pneumonia.
05:21I remember sitting there watching the sun come up and thinking, how did she get so sick?
05:29How did this happen so fast?
05:36I met Addie in a hospital bed in the intensive care unit.
05:39She was lying there, breathing quickly.
05:42She was scared.
05:44She had little infected boils all over her body.
05:48What really looked most likely when I saw her was a staph bacteria causing septic shock.
05:56And Addie fit a pattern that I recognized with community-associated MRSA.
06:00When you say community, I mean, this is what you mean that a kid picks it up in a playground
06:05with a scrape to the knee, right?
06:06Correct.
06:09The spread of MRSA, a staph bacteria that causes infections resistant to many antibiotics,
06:14has long been a big problem inside hospitals.
06:18But over the last two decades, it's also been found outside, in the community.
06:23In Addie's case, she was a skin picker.
06:25She, as do many kids, picked at her little scabs.
06:29And that was likely what introduced the staph infection.
06:34But the staph was just the start of Addie's troubles.
06:39She already had evidence of an early pneumonia.
06:42And it looked like she was about to get a lot sicker.
06:45I asked him, what were the odds of her making it getting well?
06:51What did he say?
06:52He said 30%.
06:54But he had to think about it for a minute, and I knew he was lying to me.
06:59I knew.
07:00By the time your blood has bacteria in it, you're in real trouble.
07:06The staph infection had so damaged her lungs, the doctors had no choice.
07:12To save her life, they put her on a lung bypass machine called ECMO.
07:18I remember saying, ECMO, with a squeaky voice, like, no, really?
07:25You're not really talking about ECMO.
07:28This was total life support.
07:31It's got huge tubes that are put into an artery and a vein, and the patient's blood comes out
07:42of their body, runs through the machine, and the machine does what your lung does.
07:48The tubes presented a whole new set of dangers.
07:51Those tubes can harbor bacteria.
07:54And one of the dilemmas of modern medicine.
08:00The interventions that can save you can also put you at serious risk.
08:06Any patient we put on ECMO has a much higher risk of having additional infections.
08:12That's just the nature of the beast.
08:13Is that what happened here?
08:14Correct.
08:15And she got a particularly nasty one.
08:17What was it called?
08:19Stenotrophomonas.
08:21Stenotrophomonas is an entirely different kind of bacteria from staph.
08:29Found in hospitals, it can live inside breathing tubes, and it's extremely difficult to treat.
08:36The problem with Stenotrophomonas is, even at the outset, it's already a very resistant bacteria.
08:42There are only four or maybe five antibiotics normally that are able to treat that particular bacteria.
08:52Addy was confronting the frightening new face of antibiotic resistance, a group of bacteria called gram-negatives.
09:00So can you explain to me why these gram-negatives are so stubbornly nasty?
09:05Gram-negative bacteria, it's a medical term, and it really references the armor that surrounds the gram-negative bacteria.
09:14That armor makes it very difficult for normal antibiotics to get into the bacteria and to kill it.
09:23So Stenotrophomonas is incredibly difficult to treat because it has that serious body armor surrounding it.
09:34The ability of gram-negatives to aggressively fight off antibiotics was now playing out in Addy.
09:43She was first put on one antibiotic that's good for Stenotrophomonas, and it worked for a while.
09:50And then, guess what?
09:51The antibiotic doesn't work anymore.
09:54Let's give her a different one.
09:55Well, and then it would, you know, work.
09:59A couple weeks, three weeks, and then the Stenotrophomonas would sort of, like, bloom back up, rear its ugly head,
10:08so to speak.
10:09And you're doing great.
10:10You are.
10:11Finally, one day, they said something I never thought I would hear.
10:19The Stenotrophomonas is pan-resistant.
10:23Pan-meaning resistant to everything.
10:27Like a panorama.
10:30Addy and her mother had entered the post-antibiotic era.
10:35I had to go to her and say, I don't have, I don't have options based on medical science.
10:41I've run out of options.
10:42I don't see a way out of this.
10:44I remember a long weekend went by, and they had asked me to sign the papers to let her go.
10:51And I did.
10:55There was only one hope left of saving Addy's life, to surgically remove the infection.
11:01I remember asking the doctors then about lung transplant.
11:06And they said, no, that it couldn't be done, that it would be too dangerous.
11:10The problem was that she was too sick to be transplanted.
11:13That sounds a bit strange, because you think of a transplant as the final life-saving thing you've got.
11:19But because of that resistance to Stenotrophomonas, the expected survival of transplanting her was not good.
11:29In fact, you might say close to zero.
11:32You're not going to blow bubbles?
11:34Doctors faced a question of medical ethics.
11:36Whether to risk such a valuable resource as a young set of lungs, when Addy's chances of survival were so
11:44low.
11:44What tipped the balance?
11:47I think it was Addy's mom, Tanya, who was such a strong advocate and didn't give up.
11:55Happy birthday to you.
11:59And it was also the fact that this was not an unresponsive body lying on the table.
12:05This was a young girl who was communicating with us and had temper tantrums and sparks of life,
12:14which we could all see on the ECMO apparatus.
12:16I mean, how can you say no to this, you know, living, alive human being who's communicating with you?
12:24I need a high five. That's awesome.
12:29But Addy would still have to wait in the intensive care unit, hoping to get a new set of lungs.
12:43As Addy was fighting for her life, a 19-year-old American named David Ricci was about to face another
12:49threat,
12:50on the streets of India.
12:52So after 30 hours on a train, we finally ended up in Calcutta.
13:03Here, grand negatives were spreading in frightening ways and coming from unexpected places.
13:10I wanted to experience another culture and put myself in an environment where I was serving,
13:18where I was helping people.
13:23I think India ended up changing me a lot more than I could have ever changed India.
13:34He had come here with a mission group to work in orphanages.
13:46One morning, the group headed off to work at one of those orphanages, a Mother Teresa home.
13:51It was in the slums of the slums, really, where this orphanage was.
13:55So we had to walk through all of these narrow streets that I'd never walked through before.
14:00And we basically took a shortcut through the train station.
14:04So you crossed over the tracks and then we were walking adjacent to the train tracks.
14:11And as we were going under an overpass...
14:14I was in the very back, walking, and all of a sudden, you know, out of nowhere...
14:20A train went by, and I noticed...
14:23I just remember thinking in my head that it went by, wow, that went by really quickly.
14:27The momentum and the speed hooked my sleeve and ran me over and dragged me underneath the train.
14:33The wheel ran over my leg, and I start losing a ton of blood.
14:37I just start bleeding everywhere.
14:39Ritchie was pulled from under the train.
14:42Lucky to be alive, he was rushed to a local hospital.
14:45A doctor came in.
14:47He reached up on the top shelf, and he pulls out this leather bundle.
14:52And then, you know, he takes out a big knife, you know, a big machete-type-looking saw knife.
15:01And he just starts telling all the nurses to hold me down and to hold me steady.
15:06And then he just started cutting my leg off, just hacking it off.
15:10We were standing outside, and we could hear him screaming the whole time.
15:16And then I passed out.
15:22Within 24 hours, Ritchie was moved to another hospital, and his condition deteriorated quickly.
15:30Hey, everybody.
15:31I talked to the doctors.
15:33They said I don't have that much longer.
15:39But I'll put in a good word for you.
15:43Ritchie was barely hanging on.
15:46Miss you all.
15:48And by the time his family reached India, there were new complications.
15:52They were just telling us we need to take him back in for another surgery, another surgery.
15:57And we didn't understand why.
16:02He almost had a surgery every day, and they said, you know, we've got to clean up the infection.
16:10And so, you know, I just thought it's just an infection, you know.
16:15So, I really didn't realize what they meant by infection.
16:22What Ritchie and his family didn't know was that they were on the front lines of a superbug crisis
16:28that was just beginning to unfold.
16:33The study which found the NDM-1 superbug in Delhi's water samples is making the Indian health establishment see red.
16:41Researchers had discovered a new danger.
16:44Bacteria carrying the gene that produces this NDM-1 enzyme are resistant to very powerful antibiotics.
16:50It absolutely was a bombshell.
16:52It was unexpected.
16:54The Lancet Infectious Diseases Journal found that NDM-1 enzyme in 11 different types of bacteria.
17:03NDM-1 isn't bacteria.
17:06It's actually a resistance gene that can turn bacteria into superbugs.
17:12NDM-1 is resistant to almost all antibiotics.
17:16Even more frightening, it is promiscuous.
17:19The resistance gene can jump from bacteria to bacteria, making treatable infections suddenly untreatable.
17:28But there was more.
17:31NDM-1 wasn't just in hospitals.
17:35To everyone's surprise, it was found out in the environment, too.
17:40First, from a scientific standpoint, we didn't realize that this could be done quite so easily.
17:45It meant that in places where water and sanitation was poor, where there was going to be lots of bacteria
17:50sitting next to each other, that you could have very rapid spread of resistance information across unrelated bacteria just out
17:58there in the environment, which is a hugely greater risk than if it were only to happen within the bodies
18:04of patients who had these infections.
18:07So you're saying that the bacteria were swapping this information just out there on the street without being in a
18:13person?
18:14That's correct.
18:15So they could transfer resistance genes even when they were in the same puddle of water.
18:23With the spread of NDM-1, a much wider population is put at risk.
18:30And what has health officials around the world especially worried is that NDM-1 is hearty.
18:38And it travels.
18:43After two weeks in an Indian hospital, David Ricci was flown home to Seattle and taken to the trauma unit
18:49at Harborview Medical Center.
18:55I first heard about David's case in July of 2011.
19:00I was sitting in my office doing some work and one of my colleagues, an orthopedic surgeon, Dr. Doug Smith,
19:05gave me a call and asked me if I'd known about a patient up on one of our acute care
19:10floors with a number of drug-resistant pathogens.
19:12I brought up his medical record and saw a huge amount of drug resistance, drug resistance we don't typically see.
19:18All these R's mean that the bacteria is resistant to that antibiotic.
19:24Knowing that David had come from India, I was immediately concerned, even before seeing David, about bacteria in the wound
19:31containing this new type of drug resistance.
19:36Lab results confirmed Lynch's worst fears.
19:40Ricci had brought NDM-1 into the United States.
19:43It was one of the first cases to ever be identified here.
19:48And Lynch had little to go on.
19:50There's not a lot of clinical experience with treating these bacteria anywhere.
19:54In the literature, there's no books, there's no things on it.
19:56So we had to figure out what to do for David right then and there.
20:00I get this knock on my door.
20:02And they open up the door and there's these doctors.
20:07They tell me, we need to isolate you.
20:09We need to put you on your own and quarantine you.
20:11Is that all making sense to you?
20:13Ricci was in the throes of the NDM-1 nightmare.
20:18The gene was spreading resistance to other infections in his leg.
20:23They showed us the list of them.
20:26There were about five bugs.
20:27And they said, all these infections are resistant to antibiotics.
20:34And when they said that, that's what worried me.
20:37Because I'm like, how's he going to get rid of them?
20:41Lynch tried several powerful antibiotics, but they didn't work.
20:48He had only one option left, a 1940s antibiotic called colistin.
20:54We went away from it because of its toxicity and the ability to use new antibiotics.
20:58The problem now is we don't have a lot of new options.
21:02And we're going back to some of our older antibiotics.
21:04The hardest part was watching to see what the antibiotics did to him.
21:09I started to eat away at my organs on the inside, you know.
21:11I could just feel it, just this poison rushing through my blood.
21:19The treatment was too toxic.
21:21We had to stop the only drug we had left to treat the gram-negative rods.
21:25They were in his wounds.
21:26You're telling me that he had these bugs and you had nothing left to treat him with?
21:30At this point, we had nothing left to treat him with.
21:32I just couldn't believe that there wasn't an antibiotic that would fix it, to tell you the truth.
21:39They would have to cut out more of the infection by cutting off more of Ricci's leg.
21:46But it would be months before they knew whether all of the NDM-1 was gone.
22:01A decade ago, hospitals in the New York City area became the epicenter of another highly resistant and deadly type
22:09of gram-negative bacteria.
22:12This superbug didn't come from overseas.
22:15This one was homegrown.
22:21It lives in the digestive system.
22:24And like NDM-1, it's a gene that can spread its resistance to other bacteria.
22:31It's called KPC.
22:35No one knows exactly how many patients in the New York City area have been infected with KPC, or how
22:42many have died from it.
22:45Nationally, most hospitals aren't required to report outbreaks to the government, and most won't talk publicly about them.
22:54But as part of Frontline's investigation, one of the nation's most prestigious hospitals, the Clinical Center at the National Institutes
23:02of Health, the NIH, agreed to recount how it dealt with a major KPC outbreak.
23:12It began in the summer of 2011, when a woman carrying KPC was transferred from a New York City hospital
23:20here to the NIH in Bethesda, Maryland.
23:26Talking about hospital infections is really difficult for a hospital, because what you are saying is that we all know
23:36that when you come to the hospital,
23:38there are certain risks.
23:39But we've now laid bare what are those risks.
23:45The NIH had never treated a case of KPC before.
23:50And as the patient was brought into the ICU, the staff was determined to keep the KPC from spreading to
23:57other patients.
24:00We immediately went on high alert.
24:02The equivalent of hospital epidemiology, DEFCON 5, tried to implement as many things as we could think of at the
24:11time to prevent any further spread of the organism in the hospital.
24:15They called it KPC.
24:17And so we learned later that was Klebsiella pneumoniae carbapenemase, and that's a mouthful.
24:24But we really didn't know what that meant.
24:28The patient was placed in what we call enhanced contact isolation, which means everybody who went in the room, including
24:36visitors, had to wear gloves and gowns.
24:39The room was at the end of the hall, separate from other patients.
24:43Let me just check your blood sugar, okay?
24:45But this was the intensive care unit, where patients are very sick and highly vulnerable, and that presented heightened risks.
24:53It's the kind of place where the bacteria can spread with ease.
24:57People are very busy, and there are a lot of things going on.
24:59Patients get very sick very quickly and require intervention.
25:03The bacteria can be spread on the hands.
25:05They can be spread on pieces of equipment that might go from patient to patient, so you have to be
25:10really cautious.
25:13Their efforts to contain the KPC appeared to work.
25:16When other ICU patients were tested for KPC...
25:19We found nothing.
25:22So at that point, we thought that there had not been spread of the bacteria.
25:28The New York patient ultimately recovered and was discharged after four weeks in the hospital.
25:34We really felt like we had dodged a bullet.
25:38But then, a big surprise.
25:43Five weeks later, unexpectedly...
25:46Could you do me a favor? Could you get me just a tube fixator out of the RT closet?
25:50A KPC bacteria turned up in a respiratory culture.
25:56And with it, a mystery.
26:00How this could have spread from the first patient to the second patient.
26:04They were not in the ICU at the same time.
26:06They didn't have the same caregivers. They didn't have the same equipment.
26:09So initially, we thought that it might be possible that this was a second introduction of yet another KPC organism.
26:16I was extremely concerned because the infections with these bacteria had a high mortality rate.
26:24As they began to investigate, searching for KPC on equipment and testing the patients yet again,
26:30they realized the problem was much bigger.
26:34We started finding other patients in the intensive care unit to whom the bacteria had spread.
26:42They had an outbreak.
26:45The KPC was spreading.
26:47The patients were getting sicker.
26:51And antibiotics weren't working.
26:55And we tried combinations of five, six antibiotics.
27:00We tried making oral antibiotics into intravenous antibiotics.
27:07We even got an investigational antibiotic from a pharmaceutical company.
27:12An experimental one, a test one.
27:13An experimental antibiotic. And that also did not work.
27:18Desperate to contain the outbreak, the hospital took unprecedented steps.
27:23They created a separate ICU for KPC patients.
27:27Brought in robots to disinfect empty rooms.
27:30Had monitors here reminding us to wash our hands.
27:33Built a whole wall up in the other side.
27:37We moved every patient in the ICU.
27:39Completely cleaned it.
27:40Moved patients back in.
27:43And no matter what we did, the bacteria was still, it was still spreading.
27:48We didn't know what was going on.
27:52With the hospital in crisis, genetic researchers in building 49 next door were scrambling to figure out how the KPC
28:00was spreading.
28:02We had now gotten to the point where they were identifying a patient a week and it was not clear
28:10how these patients might be related to each other.
28:14Julie Segre and her colleague, Evan Snitkin, started to compare the DNA samples of the KPC taken from the patients.
28:21Are these all the DNAs, huh?
28:23Yeah, these are all the DNAs.
28:24Each patient had a number.
28:25So this shows you, based on the DNA sequences, how we think the bacteria spread throughout the hospital.
28:30By matching the DNA, they discovered something none of them knew.
28:36Three, four, and eight were all silent carriers.
28:38And what's scary about that is they can be transmitting to other patients without anyone knowing that they even have
28:43the bacteria themselves.
28:44So this, this bacteria seemed to have been all over the hospital before they had come up positive.
28:51And the hospital didn't know that?
28:52They didn't know because this, this bacteria has the capacity to live in the stomach of patients without causing infections.
29:00For me, the data were stunning.
29:03Why, why was it stunning?
29:04Because it became very clear that we had missed the transmission sequence.
29:09The high-tech genomics revealed a disturbing truth.
29:13The outbreak would be much more difficult to contain.
29:17And to stop it, they needed to figure out exactly how the KPC was moving through the hospital.
29:24Was it on the hands of workers? Or visitors? Or on hospital equipment?
29:30And then, as they urgently searched for silent carriers throughout the rest of the hospital, their worst nightmare came true.
29:37The outbreak had spread beyond the ICU.
29:41That's a very scary moment.
29:44Suddenly, it's in the general patient population.
29:48The staff was in a panic.
29:50As they looked on helplessly, patients began to die.
29:59We felt responsible for, we are responsible for the patients.
30:03You go into a room and maybe there's a hole in your glove.
30:06It's a very complex environment.
30:09Alarms are ringing.
30:10Did you miss something?
30:10Did you forget to tell the doctor something?
30:13Did I forget to wash my hands between Mr. X and Mrs. Y?
30:17Is that why Mrs. Y got KPC?
30:22There were few options left.
30:25Dr. Gallen asked me if we needed to close the hospital or if we needed to close the hospital to
30:31admissions.
30:33Ultimately, we decided not to close the hospital, but...
30:36There was a possibility.
30:37Absolutely.
30:39Instead, they expanded testing hospital-wide and isolated all those found with KPC.
30:48Finally, six months after patient one first arrived, the outbreak subsided, almost as suddenly as it had begun.
30:58By then, 18 patients had been infected with KPC.
31:03And the ultimate tragedy, six people had died from it.
31:08Many inside NIH continued to be concerned.
31:13Do you think KPC is now gone from your hospital?
31:17Oh, no, absolutely not.
31:19I think that we have to be extremely vigilant in the coming years because of the increasing rise, the increasing
31:29prevalence of KPCs in the United States.
31:36The increasing prevalence of threats, like KPC, became the focus of a five-year study at the world's largest medical
31:43center in Houston.
31:46Using cutting-edge genomics, researchers analyzed infections from nearly 1,800 patients and in May 2017 announced a startling discovery.
31:58We were surprised, greatly surprised, when we found a new type of bacterium that had never been described in great
32:07abundance anywhere in the world.
32:11This new type is called Klebsiella CG307, and it can be deadly.
32:18Has it killed people?
32:19People die with this organism sometimes, yes.
32:22Excuse me.
32:23The rare superbug was found in a third of the samples taken from patients.
32:27Now, the question that we don't know the answer to is, why is it abundant?
32:32But it's clearly been abundant here, and undoubtedly in other Houston hospitals as well.
32:40And there was a more troubling mystery.
32:42Where did it come from?
32:43We don't know exactly where this bacteria came from, but probably many patients brought it into the hospital,
32:53and we now know that this is a common organism in our community.
33:00The Houston study brings it clear, and it puts it there in black and white.
33:04The threat of antibiotic resistance is dynamic and ever-evolving.
33:09Not only at stake are people's lives, but as more resistance occurs, and I mean nationally, not just in our
33:19hospital,
33:19there's more of a probability of creating an organism that is now resistant to every antibiotic.
33:30The prospect of life without antibiotics is barely imaginable for a world that has had a cheap and plentiful supply
33:37of them since the end of World War II.
33:40They are a staple of modern medicine.
33:43It's hard to recall a time without them, when an infected cot could kill a healthy young person in a
33:49matter of days.
33:51But it's now clear that we are heading back in that direction, that the miracle of these drugs is slipping
33:58away.
34:00Antibiotics are unique drugs.
34:03They're not like any other class of drugs.
34:07Fifty years from today, the cholesterol drugs we have now will work just as well as they work today.
34:12The cancer drugs we have now will work just as well as they do today.
34:16That's true of all the other drug classes.
34:18Antibiotics are the only class of drugs that the more we use, the more rapidly we lose.
34:24When you use it, it becomes less effective for me and vice versa.
34:28That is the essence of antibiotic resistance.
34:32The more you expose a bacteria to an antibiotic, the greater the likelihood that resistance to that antibiotic is going
34:41to develop.
34:41So the more antibiotics we put into people, we put into the environment, the more opportunities we create for these
34:49bacteria to become resistant.
34:53But people forgot about the danger of resistance because the drugs were so effective.
34:59And what they had forgotten was the warning that Alexander Fleming himself, the man who discovered penicillin, gave us in
35:051945.
35:06That resistance was already being seen, and the more we wasted penicillin, the more people were going to die of
35:12penicillin-resistant infections.
35:15Bacterial resistance is largely inevitable, but it's also something that we have certainly helped along the way.
35:22We have fueled this fire of bacterial resistance.
35:26These drugs are miracle drugs, these antibiotics that we have, but we haven't taken good care of them.
35:34Public health officials estimate that one-third of all antibiotic use in the U.S. is either unnecessary or inappropriate.
35:43And in overusing these antibiotics, we have set ourselves up for the scenario that we find ourselves in now where
35:51we're running out of antibiotics.
35:54But the growing scarcity of effective antibiotics isn't just a problem of overuse.
36:00It's also been driven by what's happening inside the drug industry itself.
36:05The place where it started to turn really challenging, I'd say, would be in the 80s and the 90s,
36:10when we began to see occasional bacteria that were very hard to treat.
36:15And it became less obvious that you were able to invent new antibiotics.
36:20And the brand-new things just weren't coming at the same pace.
36:25And then in the 90s, in the first part of this century, we began to see resistant bacteria,
36:30for which we really didn't have very much or anything at all, and we had nothing coming to treat them.
36:38That's because most major drug companies were pulling out of the antibiotic research field,
36:43just as the gram-negative threat was worsening.
36:48One of the last companies to stay was Pfizer, which had made its name on antibiotics.
36:54By the mid-2000s, it had set its sights squarely on the gram-negative problem.
37:00We thought there was medical need. That's what really matters.
37:03And we thought that, given our history in being able to develop penicillin, the antifungals, you know, antibiotics,
37:13that, in fact, if we put our minds to it, that we would succeed.
37:18But this is a highly risky and unpredictable enterprise.
37:22Despite the risk, Pfizer built a world-class research team in Groton, Connecticut,
37:28and brought in a veteran in gram-negative research, John Quinn.
37:33In 1983, when I finished my training, almost every pharmaceutical company had an antibiotic development team.
37:40And by the time I landed at Pfizer in 2008, we were really down to three big guys
37:46and some smaller companies, biotechs and so on.
37:49And I think all of us felt that, you know, we had a moral obligation to continue to work in
37:55this area.
37:56There was a pressing clinical need. Most companies had abandoned the field, and we were still in the game.
38:01We were proud to still be in the game.
38:03Quinn and his team believed they were on to something big,
38:07several different compounds to treat gram-negatives.
38:11The potential breakthroughs got the attention of the company's science advisors, including Brad Spellberg.
38:16I felt that their pipeline was probably the most comprehensive and important antibacterial pipeline in the world,
38:24focusing on the types of bacteria that we're really having severe problems with right now.
38:31Which are the...?
38:32The highly resistant gram-negative bacteria.
38:35These would have solved problems and saved lives had they been successfully developed.
38:42But bringing these drugs to market faced the economic paradox of antibiotics.
38:48If you need an antibiotic, you need it only briefly.
38:50Indeed, that's the correct way to use an antibiotic. You use it only briefly.
38:54And from an economic standpoint of a developer, that means you're not getting the return on the investments you've made,
39:00because you've spent between $600 million and a billion dollars to bring that new antibiotic to market.
39:05Wait, I mean, it costs up to a billion dollars to bring a new drug to market?
39:08It can easily cost up to a billion dollars to bring a new drug to the market.
39:12And the initial reaction to it is, that's great, and let's not use it, let's use it as little as
39:18possible.
39:19So here's a large company saying, I have, I can make billions off cholesterol drugs, blood pressure drugs,
39:27arthritis drugs, dementia, things that I know patients are going to have to take every day for the rest of
39:32their lives.
39:32Why would I put my R&D dollars into the antibiotic division that isn't going to make me any money,
39:38when I can put it over here?
39:40So here's the deal.
39:41That's going to make a lot of money for the company. I answer to the shareholders.
39:46That was the problem facing Pfizer in 2011.
39:49Don't kid yourself.
39:51Its stock had plummeted on Wall Street, and its blockbuster cholesterol drug, Lipitor, was about to lose its patent.
39:58I received an email on my BlackBerry that there was a mandatory emergency meeting in two hours.
40:06It can't be good.
40:07So I called in for the meeting and was told that the announcement had been made that the Groton facility
40:12was going to be closed.
40:14The company ended 70 years of leadership in antibiotic development, leaving its search for a gram-negative cure unfinished.
40:23The external people who I spoke to, many of whom are my personal friends, said to me,
40:28Well, Pfizer's just doing what other companies have done. There's nothing particularly wrong with that. It's not immoral. We are
40:35a capitalist society.
40:38In 2013, we asked Pfizer to explain the decision.
40:42I get the sense that you have to make some very ruthless decisions about where to put the company's capital,
40:49about where to invest, where to put your emphasis.
40:51And when you pulled out of gram-negative research like that and shifted to vaccines, do you look back on
40:57that and say, you know, we learned something about this?
41:00These are not ruthless decisions. These are, you know, portfolio decisions about how we can serve medical need in the
41:08best way.
41:09We want to stay, you know, in the business of providing new therapeutics for the future. Our investors require that
41:17of us.
41:17I think society wants a Pfizer to be doing what we do in 20 years. We make portfolio management decisions.
41:27In 2016, Pfizer decided to reenter the antibiotic market and bought several drugs under development.
41:34Like other large pharmaceuticals, though, it is still not investing in research.
41:39There is an increasing recognition that antibiotics are not a good thing to run off a pure capitalistic market.
41:49We need to switch from an entrepreneurial business model where you maximize sales to other payer mechanisms, where the goal
41:57is society can say, we want these kinds of antibiotics developed and we're going to help you out.
42:03We're going to decrease your cost and risk. In return on the back end, we're going to have some say
42:07in how it's used so it doesn't get abused.
42:13In Washington, the federal government has been ramping up its involvement in the superbug fight.
42:19Two years ago, the Obama administration unveiled a national plan coordinated by the Department of Health and Human Services.
42:27The point person for the effort now is Christopher Jones.
42:30Under the national action plan for combating antibiotic resistant bacteria, which was released in 2015, we now have an overarching
42:38framework and structure for addressing this issue across the federal government.
42:43We have a plan.
42:43We have a plan that has specific actions that are being worked on every single day.
42:48And I think it's reflective of the investments we've been making around surveillance, stewardship, developing new products, developing new diagnostics,
42:58and increasing international collaboration on the issue.
43:01For a long time, people have been warning that the pipeline of new antibiotics is running dry. How's that going?
43:07We're investing $250 million over five years for the early stage development of antimicrobials.
43:14I think the next phase as we start to think about products that really show promise in early phases is
43:20how do we continue to support their development.
43:23And I don't think we've fully landed on what that strategy looks like, but we do have to rethink how
43:28we reward companies.
43:30And that's, again, ongoing conversations.
43:33But some say the government should be playing a larger role.
43:37Is there more that needs to be done?
43:39Where we need to focus on now is using less antibiotics.
43:42We need to create policies and regulations.
43:47If we publicly reported antibiotic use, attach requirements to hospitals you have to report, that public shaming effect will drive
43:57antibiotic use down.
43:58And these are all the M28s?
44:00Yes, sir.
44:01Even as the government's strategy is taking shape, the Trump administration has proposed funding cuts of up to 20%
44:07to programs and agencies that combat antibiotic resistance.
44:11What would be the significance and the impact of new budget reductions in antibiotic resistance?
44:17To your point, yes.
44:18A lot of what we're doing requires investments.
44:22It requires resources.
44:23If there is less money to spend, there are tough choices that have to be made, things that can't be
44:28done.
44:29I'm very concerned about it, and I think we all should be.
44:32I think the gains that we have made have been largely because of investment.
44:39And if we cut back, you're going to see an even faster evolution of resistance and spread of resistance and
44:46way fewer countermeasures being developed to combat it.
44:52Last year, the warnings became even more dire.
44:56Drug-resistant bacterial infections are on track to kill more people than cancer.
45:02One international report predicted...
45:04By 2050, superbugs could kill 10 million people a year.
45:09Now we are seeing bacteria that are resistant to the absolute last stop on the train, the colistin.
45:16And so for those patients, there are no options left.
45:20So those patients truly have gone back in time.
45:23They are back in the pre-antibiotic era, and they will recover from those infections or will die from those
45:31infections, and there's nothing we can do for them.
45:37As we reported in 2013, NIH never did fully rid itself of the deadly superbug KPC.
45:45A year after the outbreak, a young man came to the hospital because of complications from a bone marrow transplant.
45:53While he was there, he contracted KPC and died, the seventh victim of the outbreak.
46:01I guess if I had a major message, it would be that it's never going to end.
46:06So this organism and organisms like this are going to be with us until the cows come home.
46:14And we have to learn how to deal with them.
46:17We have to change our culture in the hospital.
46:21KPC has been found in hospitals in all but two states, and that's just the hospitals that are voluntarily reporting
46:28it.
46:40As for David Ricci, it took three surgeries and another round of highly toxic antibiotics before doctors believed they had
46:49removed all the NDM1 from his leg.
46:58You know, there's no muscle left on it, and I only got about six inches left, and the bone stops
47:05there.
47:06So far, Ricci has remained healthy, though not entirely free from the fear of NDM1.
47:15You know, my doctors were pretty straightforward with me.
47:17They were very honest and said, you know, there is a good chance that this infection might not go away.
47:21Might not ever go away.
47:22Yeah, yeah.
47:23They said, you know, we don't have enough experience to know what's going to happen.
47:34NDM1 has now spread to at least 70 countries.
47:39And here in the U.S., more than 200 cases have been reported.
47:45So David was actually sort of a harbinger of something to come.
47:49David was an example of something that's already here.
47:54So there are entire continents that have this major problem, public health problem already.
48:02David was simply a sample of that population, new to us.
48:07And that's key because hospitals in any city in the country are going to have patients from all over the
48:13world.
48:13That globalization, that mobility is going on now.
48:17This is already here.
48:23All right, Addy.
48:25Let there be light.
48:26This is the day that the Lord has made.
48:29Addy Rerasich was finally able to return home.
48:31Yeah, but it's, like, not fun.
48:35Let there be no light whatsoever.
48:38She received the double lung transplant she'd been waiting for.
48:43Hi.
48:45It was like bringing home a premature baby.
48:47Yeah.
48:47We brought home monitors, and she couldn't do anything for herself.
48:52She couldn't even turn over in the bed.
48:54She couldn't turn side to side.
48:56That's how weak and contracted and debilitated she was.
49:01So how are you doing now?
49:04Basically, I'm fine.
49:07Nothing seems out of whack right now.
49:10I seem pretty, I feel pretty good.
49:14I look pretty much like I did before.
49:17I have all my friends back.
49:18Did you understand what was happening to you?
49:20Mm-mm.
49:21No.
49:22Did anybody talk about infection and what that, what infection meant?
49:26No.
49:27Basically, what I was told is I'd say I want to go home.
49:31And she'd say, um...
49:35She'd say I couldn't make the drive home ever.
49:39Like, I was too sick to go home.
49:45Okay.
49:46Everything's hard for Addie now.
49:48Everything's a battle.
49:51Um...
49:51Prescriptions.
49:52She has to take a handful of pills twice a day.
50:00We have to worry constantly about, you know, picking up a bacteria or a virus.
50:06She's had pneumonia five times.
50:09Bacterial pneumonia that had to be treated with antibiotics.
50:12And every time, I wonder, is this the time that we're going to come up against the bacteria
50:20that they don't have anything to treat it with?
50:30I think for lung transplants, the survival rate, about 80% make it a year.
50:36And about 50% make it five years.
50:39And every year after that, the risks just go up.
50:48People might say, the story of Addie is horrible, but that won't happen to my daughter.
50:53Could this happen to anybody?
50:56It happened to Addie.
50:57She was healthy.
50:58It could happen to anybody.
50:59It could happen to your next-door neighbor.
51:01It could happen to your child.
51:03It could happen to anybody.
51:04Now, I'm not here to practice doomsday thinking, but those bacteria,
51:09are out there.
51:10And they're out there in healthy people in the community.
51:13If you don't mind standing up, you can walk around there.
51:15Hello, Caleb.
51:16Sure?
51:19The average person thinks, oh, I have an infection.
51:21I take an antibiotic.
51:22I get better.
51:24Yeah, it's not that simple anymore.
51:26Morning, Caleb.
51:27How you doing, sweetheart?
51:29I'm good.
51:30I know.
51:31Addie didn't get better, did you?
51:32No.
51:33She never did get better.
51:35Really.
51:36She didn't.
51:37She had to have surgery and take the infection out.
51:43But...
51:44May have saved her life.
51:46Mm-hmm.
51:47For now.
51:50Bought her time.
51:53That's what happened.
51:55We bought her some time.
51:57And I am grateful for every minute of it.
52:02Hi, Mom.
52:04Nice to meet you.
52:06See you soon.
52:07Hi, I'm Addie.
52:10I don't think we ever met.
52:11I remember you.
52:12I know I've seen you somewhere before.
52:14Yeah, me too.
52:15I know.
52:17Are you my nurse?
52:19Yeah.
52:28Something happened to our children, which then led to autism.
52:31The debate over vaccines.
52:3312 epidemiological studies showed that that wasn't true.
52:36Parents should have some input.
52:38It's so frustrating for public health officials.
52:40But with measles making a comeback.
52:41102 cases, 14 states.
52:43Herd immunity is real science.
52:45It keeps our children from getting sick.
52:47Should vaccination be a choice?
52:49Some choices impinge on the health of others.
52:52The Vaccine War.
52:58Go to pbs.org slash frontline to learn more about how to protect yourself from superbugs.
53:04We have to be extremely vigilant.
53:07Watch our follow-up investigation, The Trouble with Antibiotics, about superbugs and the animals
53:12that we eat.
53:13We're using 30 million pounds of antibiotics each year to raise our animals.
53:17And connect to the Frontline community.
53:19Tell us what you think on Facebook and Twitter.
53:22And sign up for our newsletter at pbs.org slash frontline.
53:28For more on this and other Frontline programs.
53:29Just watch our show.
53:30And sign up for our newsletter.
53:39We'll see you in the next month.
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53:40Bye.
53:41Bye.
53:41Bye.
53:42Bye.
53:46Bye.
53:46Bye.
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53:54For more on this and other Frontline programs, visit our website at pbs.org slash Frontline.
54:10Frontline's Hunting the Nightmare Bacteria is available on DVD.
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