The Trouble with AntibioticsView film
David E. Hoffman
DAVID E. HOFFMAN, Correspondent: [voice-over] For the past two years, I’ve been investigating the emergence and spread of nightmare bacteria, superbugs that are increasingly resistant to even the strongest antibiotics.
[on camera] The bacteria are fighting back, and they’re defeating the drug.
DAVID E. HOFFMAN: [voice-over] I’d been tracking the phenomenon through hospitals around the country, where doctors have been dealing with patients infected by these superbugs, which go by names like KPC and NDM1.
PHYSICIAN: All these R’s mean that the bacteria is resistant to that antibiotic.
DAVID E. HOFFMAN: I’d found outbreaks that have paralyzed some of our best hospitals.
NURSE: And no matter what we did, the bacteria was—it was still spreading.
DAVID E. HOFFMAN: More than 20,000 people a year are dying from these infections, and as many as two million get sick from them.
What’s become apparent is that these infections are being fueled by the overuse of antibiotics, creating bugs we can’t kill. But the more I looked into it, the more I saw there was another dimension to the story. It turns out most antibiotics aren’t even used by humans, they’re used on farms.
Getting onto a farm wasn’t easy. The use of antibiotics in agriculture has become such a sensitive subject that most farms won’t let cameras in. But one in north Georgia agreed, as long as we didn’t reveal its name.
[on camera] What’s your big goal?
[voice-over] The farm’s veterinarian, Chuck Hofacre, showed me how antibiotics have become essential to the industrial-scale farming.
Dr. CHUCK HOFACRE: My big goal is to prevent disease, and that’s what almost all food animal veterinarians today focus more on, stopping disease introduction, preventing diseases from happening, rather than having sick chickens and animals that are suffering.
I’m looking at trying to prevent any health issues in this small city of chickens of 100,000.
DAVID E. HOFFMAN: [on camera] It is like a small city, isn’t it.
Dr. CHUCK HOFACRE: Yes, because once they get sick, just as in a city, the disease can then spread through the population fairly quickly.
DAVID E. HOFFMAN: [voice-over] This is what Hofacre wants to prevent.
Dr. CHUCK HOFACRE: This chicken was sick because of an intestinal disease.
DAVID E. HOFFMAN: [on camera] So this is a signal to you that, time to use an antibiotic to prevent this from spreading.
Dr. CHUCK HOFACRE: That’s correct.
DAVID E. HOFFMAN: Chuck, what do we have here?
Dr. CHUCK HOFACRE: Well, this is an antibiotic called lincomycin.
DAVID E. HOFFMAN: [voice-over] Antibiotics like this are regularly put in the drinking water or added to the feed of healthy animals, most of the time without a prescription.
Dr. CHUCK HOFACRE: Empty the antibiotic into the water. Water coming out of this bucket with the antibiotic will be injected into their water. And then that water will then go on into the chicken house, and we’ll be at the proper dosage.
DAVID E. HOFFMAN: It’s estimated that as much as 70 percent of all antibiotics sold in the United States go to farms.
Dr. CHUCK HOFACRE: They drink out of these nipples and they eat from these feeders, and that helps the flock grow better. The farmer does better because they have more pounds of meat, gives consumer a cheaper food supply. The chickens are healthier, so healthier chickens mean a healthier product for the consumer, as well.
DAVID E. HOFFMAN: But increasingly, this widespread use of antibiotics in animals has been raising concerns.
[on camera] Is it possible that there’s a pathway—I’m thinking particularly of resistance. You know, could it go in bugs from the chicken house to the family table?
Dr. CHUCK HOFACRE: We don’t know how often that occurs. We think that it probably occurs at a very, very low rate. That linkage is very difficult to—to connect the dots.
DAVID E. HOFFMAN: [voice-over] Scientists have long been looking for connections between these dots, trying to understand whether the use of antibiotics on farms is contributing to antibiotic resistance that threatens the health of people.
As I dug in, I began to find new evidence that was complicated and surprising. My investigation took me to Flagstaff, Arizona, where I’d heard about some of the newest research being done. Flagstaff’s hospital has seen a rise in urinary tract infections that are increasingly resistant to antibiotics.
ELIZABETH DuPREEZ, Pharm.D., Infectious Disease Pharmacist: OK, we have the lady in room 12. She came in two days ago with the E. coli in her urine.
DAVID E. HOFFMAN: [on camera] Right.
ELIZABETH DuPREEZ: Well, it came back this morning as being a resistant organism, so we had changed from zosyn to a carbapenem.
DAVID E. HOFFMAN: [voice-over] These infections strike an estimated eight million Americans every year. Like in Flagstaff, doctors around the country are struggling to treat them.
ELIZABETH DuPREEZ: Looks like it’s only preliminary, but looks like it’s a gram-negative rod.
We’re seeing a lot more patients that were previously normally healthy have to be admitted because they’ve gone through multiple outpatient courses of antibiotics, they haven’t improved, and at the point that they come in, that bacteria has gone into their bloodstream. And that requires immediate hospitalization.
You don’t have a normally healthy 30-year-old woman come in, who’s never been in a hospital, with a resistant urinary tract infection that’s moved to her blood. Where did she get that organism from?
DAVID E. HOFFMAN: This problem caught the attention of a genetic researcher who had a theory about where some of these infections could be coming from.
LANCE PRICE, Ph.D., Microbiologist, T-Gen Research Institute: So this is the meat section, and this is where our team spent a good part of their year last year, buying two packages of every brand of chicken, turkey and pork.
WOMAN: No expiration.
LANCE PRICE: This is chicken. I want to get some organics, so I’ll get two of these organics.
DAVID E. HOFFMAN: Lance Price started sampling the meat supply in Flagstaff in 2012, trying to figure out if resistant bacteria from farms is ending up on the meat we buy.
LANCE PRICE: We started this study because we had this hypothesis, this theory that food could serve as a source of E. coli that then went on to cause urinary tract infections.
Could I get two pounds of the ground turkey? But could I get it in two separate packages?
DAVID E. HOFFMAN: Price isn’t concerned with the trace amounts of antibiotics that could be in meat. He’s looking for antibiotic-resistant bacteria that could be on the meat and cause dangerous infections if they end up on our hands or our kitchen counters, or if the meat isn’t cooked enough.
LANCE PRICE: We’re producing nine billion food animals, and by using antibiotics in food animal production, we’re creating drug-resistant pathogens that can then go on to cause drug-resistant infections in you and me.
WOMAN: These guys expire on the 6th.
LANCE PRICE: The problem with urinary tract infections is that if you get a bladder infection with E. coli and it’s antibiotic-resistant, and the doctor goes to treat you and that treatment fails because the bacteria is resistant, then it can get in the kidneys. And once it has—once it’s in your kidneys, it has access to your blood, right, and so then you can get what we call sepsis, which kills 40,000 Americans each year.
OK, thanks a lot.
We’re going to put it into a broth. We’re going to put it in the incubator and we’re going to see if we can grow E.coli from it.
DAVID E. HOFFMAN: What Price wanted to know is whether the meat aisles of Flagstaff’s supermarkets were the source of some of the dangerous urinary tract infections that were showing up in the local hospital. His study would take several years.
The widespread use of antibiotics on farms goes back decades. They were first used on animals in the 1940s.
ANNOUNCER: [promotional film] Among the many valuable new products created in agricultural laboratories are mass-produced antibiotics—
GAIL HANSEN, D.V.M., Pew Charitable Trusts Antibiotic Campaign: It was at a time when agriculture was really changing and really becoming much more of a—at that time, it was not a pejorative, but it was an industrial model. So farms were getting bigger. Animals were getting put closer together.
When you put the animals closer together and you have them confined, then it’s a lot easier to pass diseases back and forth. Giving them a little bit of antibiotic sort of seemed to fix that problem, or sort of put a Band-Aid over it anyway.
DAVID E. HOFFMAN: But there was another benefit, one they had not anticipated.
ANNOUNCER: [promotional film] The power to promote growth. Note the weight of a chicken raised for eight weeks on a regular feed. Now another chicken nourished for the same period on regular feed plus teramycin, a 15 percent increase in growth.
RICHARD CARNEVALE, D.V.M., Vice Pres., Animal Health Institute: They had discovered that if you add these drugs to the feed of animals, they were very useful in increasing the productivity of the animal. They kept them healthy. That was the main thing. They reduced loss in sicknesses in their animals. And they also discovered that it gains the same amount of weight on less feed. Feed is a very big cost.
ANNOUNCER: [advertisement] Want something special for Sunday dinner? Chicken inspected and graded is now thrifty every day.
Dr. RICHARD CARNEVALE: People don’t realize how expensive chicken used to be.
DAVID E. HOFFMAN: [on camera] So antibiotics helped us get to inexpensive chicken.
Dr. RICHARD CARNEVALE: Inexpensive and higher quality chicken, yes, higher quality chicken, and pork and beef, as well.
DAVID E. HOFFMAN: [voice-over] With the help of antibiotics, American meat production has tripled over the last 50 years. But with the growth also came concerns. As early as the 1960s, the British government sounded an alarm in a study called the Swann report.
Dr. GAIL HANSEN: This was a milestone report. They said that antibiotics shouldn’t be used to get the animals to grow faster because one of the unintended consequences was antibiotic resistance. Yes, it was an economically short-term good, but in the long term, antibiotic resistance was a real problem.
DAVID E. HOFFMAN: But the report did not establish a direct link between farm antibiotics and human illness, and that’s still the question today.
CHRISTINE HOANG, D.V.M., Asst. Dir., American Veterinary Medical Assn.: I’m not saying that, you know, the use in animal agriculture doesn’t contribute to resistance at all. Of course, we see resistance in veterinary medicine from the use of antibiotics. But there’s a lot of unknowns, as well. We really have not shown that direct pathway from, you gave this animal that drug and some person somewhere down the line ate meat from that animal, and they now have a resistant infection because you gave that drug way back here.
DAVID E. HOFFMAN: In central Pennsylvania, I came across researchers tackling the scientific challenge in a different way. They’re trying to track how resistance might travel through the environment from farms to people.
JOAN CASEY, Ph.D., Epidemiologist: We came to central Pennsylvania for this research because there are a lot of swine animal feed operations here.
DAVID E. HOFFMAN: Joan Casey is an epidemiology fellow at the University of California at Berkeley. Five years ago, when she was studying for her Ph.D., she became interested in antibiotic resistance.
JOAN CASEY: I basically just started reading about it and trying to find out what was known about antibiotic use and farm animals.
DAVID E. HOFFMAN: Casey found research from Europe suggesting that an antibiotic-resistant bacteria called MRSA, which can cause deadly skin infections, was traveling from pig farms to people. She wanted to know if the same thing was happening here.
JOAN CASEY: --if people living close to huge animal feeding operations were at risk for getting infections from these operations.
DAVID E. HOFFMAN: To try to answer that question, Casey turned to Geissinger, one of central Pennsylvania’s largest health care providers, where she joined forces with Brian Schwartz.
BRIAN SCHWARTZ, M.D., Environmental Epidemiologist: Almost four million people live in this region, right?
DAVID E. HOFFMAN: As a senior researcher, he had has access to a trove of medical data.
Dr. BRIAN SCHWARTZ: We were able to get about a 160 million electronic records on about 450,000 patients from the region.
DAVID E. HOFFMAN: [on camera] And what did you find?
Dr. BRIAN SCHWARTZ: Total MRSA from 2001 to 2009, straight up, incidence up every year.
DAVID E. HOFFMAN: [voice-over] They found MRSA infections had been rising as much as 34 percent a year in central Pennsylvania. And the patients weren’t typical.
Dr. BRIAN SCHWARTZ: People are getting MRSA who are not like the ones who used to get it. They’re not old, sick people. These are young, healthy people.
DAVID E. HOFFMAN: And when they compared that data with the location of pig farms in the area, a pattern started to emerge.
JOAN CASEY: This is the location of where all of the people with MRSA infections live. Each red dot is a person that had a MRSA infection. So these are all their home addresses.
DAVID E. HOFFMAN: [on camera] Right.
JOAN CASEY: So what I can show you here is the location of the swine operations in this region. Each of these barns represents a large confined animal feeding operation.
DAVID E. HOFFMAN: So let’s look at this next one.
JOAN CASEY Yes, so let me show this to you.
DAVID E. HOFFMAN: So what is this?
JOAN CASEY: So there’s some nice overlap you’ll see between where the MRSA cases are and where these large swine farms are. You can see that there’s some people with these infections living very close to animal feeding operations. And this is the only study that’s really been done in the United States that’s looked at rural areas and MRSA infection.
DAVID E. HOFFMAN: [voice-over] Their theory was that the MRSA causing some of the infections was coming from pig manure.
JOAN CASEY: Every year in this area, there’s about 600 million gallons of animal manure spread onto crop fields.
Dr. BRIAN SCHWARTZ: When you have antibiotics in animal feeds, the manure is loaded with undigested antibiotics. It’s loaded with antibiotic-resistant bacteria. And it’s loaded with the genes that the bacteria can transfer back and forth to each other that allow them to become resistant.
DAVID E. HOFFMAN: [on camera] But help me understand. How does it get from being put on a field as fertilizer for crops to threatening me, living in my house?
Dr. BRIAN SCHWARTZ: So you put the manure on that crop field, and it doesn’t rain for a month. And the soil gets dusty, and a big wind comes by. It goes airborne. It can travel by air. Or conversely, a big rainstorm comes by and all the MRSA gets washed off into the drainage, off of the field and into the local streets and onto the neighbors’ lawns.
JOAN CASEY: We actually found that people living closer to these farms and to the crop fields that are located nearby were about 38 percent more likely to have a MRSA infection than people living farther away. Right now, I think the best hypothesis that we have is that it’s coming from industrial agriculture.
DAVID E. HOFFMAN: [voice-over] But to the farmers and drug makers, the study was just more unsettled science and speculation.
RICHARD CARNEVALE, D.V.M., Vice Pres., Animal Health Institute: Well, I think the study was very interesting, and it showed some associations. But I think the implication is that antibiotic use somehow caused the problem, and there’s no evidence that that is the case. They didn’t test any of the manure, so they have no data on what was actually in the manure. So their study was more speculative than anything.
DAVID E. HOFFMAN: [on camera] Why didn’t you just take a trowel and dig up some of that crop field where the manure was and test it yourself as part of the study?
Dr. BRIAN SCHWARTZ: Well, it costs a lot more money and we didn’t have the money for that. And you also need permission to go on people’s crop fields. And in general, getting access to the farm operations has not been easy.
DAVID E. HOFFMAN: In the end, though, aren’t you really speculating about the link based on a pattern?
JOAN CASEY: We have not made any definitive links, but I think there’s mounting evidence that there’s a problem.
DAVID E. HOFFMAN: [voice-over] Making sense of the science isn’t easy. I went to the CDC in Atlanta, where they closely track antibiotic resistance.
[on camera] Is it possible that the use of antibiotics in animals is breeding resistance, that farms, like hospitals, are becoming a place where resistance comes from?
TOM CHILLER, M.D., Associate Director, CDC: Well, it’s not only possible, I mean, it’s happening. I mean, we see resistance in pretty much everywhere in everything we test. So there is a certain amount of resistance in cattle, in pigs, in chickens, in humans, in the retail meat that we buy in stores. Anywhere you use antibiotics, you’re going to have resistance and propagate resistance.
DAVID E. HOFFMAN: [voice-over] Yet the CDC acknowledges the lack of conclusive science.
Dr. TOM CHILLER: It’s very challenging to link the use of a particular antibiotic in a particular herd of animals to a particular human illness. I mean, that is really the challenge. So going from point A to B to C to D to E to F, tracing that bacteria all the way to person A with resistance A—I mean, that’s very challenging to do because there are lots of steps in between.
DAVID E. HOFFMAN: The agency with the authority to regulate antibiotics is the Food and Drug Administration. Inside their archives, I found the story of how the agency tried to reduce the use of farm antibiotics nearly 40 years ago. It was 1977. The FDA had a new commissioner, a Stanford biologist named Donald Kennedy.
DONALD KENNEDY, Ph.D., FDA Commissioner, 1977-79: Members of my staff got some documents to me that convinced me that we really had a difficult problem to deal with. Livestock had been dosed up just to make the animals put on weight faster.
DAVID E. HOFFMAN: One of Kennedy’s closest aides was Tom Grumbly.
TOM GRUMBLY, Fmr. FDA Policy Assistant: He had passion about this issue almost from the beginning. And the way he would express it was, “Look, I don’t know whether antibiotic resistance is going to come more from the human use of antibiotics or from the animal use, but I know that there’s really no difference.”
DAVID E. HOFFMAN: Based on the advice of top scientists, Kennedy proposed restrictions on two of the most widely used farm antibiotics, penicillin and tetracycline. He feared that by overusing these drugs, farmers were fueling antibiotic resistance and threatening the health of people.
DONALD KENNEDY: We’re creating resistant organisms that may ultimately transfer that resistance to organisms that cause human disease.
I thought we were doing exactly the right thing. The trouble is that you don’t always find that as easy as you would hope.
DAVID E. HOFFMAN: Opposition to the proposal was immediate. Farm lobbies and industry groups attacked it as theoretical speculation and said it would be financially ruinous. One of the most vocal opponents was the animal drug makers’ group, the Animal Health Institute.
[on camera] AHI was against that at the time. Do you remember why?
Dr. RICHARD CARNEVALE: Well, I wasn’t at AHI at the time, so I don’t know. And you say that they were, but I don’t know that they were. I mean, do you have—is there some documents that you’ve seen?
DAVID E. HOFFMAN: There is. This is actually AHI’s proposal to—at the time, to the docket. AHI said that the commissioner’s proposal is “wholly illogical,” would result in an “arbitrary and capricious” and thus illegal regulation.
Dr. RICHARD CARNEVALE: I think in the case of penicillin and tetracyclines, it was a theoretical concern. Back then, they didn’t really have good risk assessment at the time. They really couldn’t put the whole picture into place as to, “OK, this can happen. We know it can happen in the laboratory. Does it happen in the real animal? And what is the real risk to public health?” I think that was where they were missing the data.
DAVID E. HOFFMAN: [voice-over] The industry turned to their allies in Congress, and one of their closest was Mississippi congressman Jamie Whitten.
TOM GRUMBLY: His informal title was the permanent secretary of agriculture, a title he held for several decades.
DAVID E. HOFFMAN: Whitten chaired the subcommittee that controlled the entire FDA budget.
TOM GRUMBLY: We were at the mercy of Representative Whitten, who basically made it clear that unless we got much more scientific evidence, he was going to cut the heck out of the FDA budget,
DAVID E. HOFFMAN: [on camera] So he said that unless you guys would study this and get more information—
TOM GRUMBLY: He was going to cut the budget.
DAVID E. HOFFMAN: And that’s a pretty serious threat from Whitten, right? I mean, he’s a powerful guy.
TOM GRUMBLY: That was no threat, that was no brag, that was truth. He would have.
DAVID E. HOFFMAN: [voice-over] The proposal was shelved.
[on camera] When you posed this in 1977, it wasn’t settled science. You said you were confident about it. And I just wondered, did we know enough?
DONALD KENNEDY: I think there was a search for what we used to call the smoking gun—that is, a particular antibiotic carried over, and so forth. I think it was vulnerable enough to the argument that “You haven’t really showed us the smoking gun” that it failed in its time.
DAVID E. HOFFMAN: So after you tried and pushed for this and then it got blocked, did anything ever happen?
TOM GRUMBLY: Well, it kind of went into the deep freeze for a long time. You know, people just basically said, you know, “This is in the too hard category.” And until we get real evidence or evidence of people—I hate to say it—dropping in the streets, so to speak, from antibiotic resistance, that nobody’s going to do anything about this.
DAVID E. HOFFMAN: [voice-over] But there’s new evidence emerging that FDA was on to something back in 1977. On a north Texas feedlot, I met two veterinarians who have spent years working with the cattle industry.
MORGAN SCOTT, Ph.D., Vet. Epidemiologist, Texas A&M Univ.: Guy and I have been working together for last 10 or 12 years on many of these issues, actually.
GUY LONERAGAN, Ph.D., Vet. epidemiologist, Texas Tech. Univ.: We’ve done multiple projects on antibiotic resistance. We’ve been working extensively on this, and making progress. It’s an evolving progress, but we’re making progress.
DAVID E. HOFFMAN: Guy Loneragan of Texas Tech University and Morgan Scott of Texas A&M noticed something unsettling in their research with cattle. An important antibiotic called cephalosporin was losing its effectiveness. Bacteria were becoming resistant to it, so when the cattle got sick, they were harder to treat.
But the scary part was that unlike most farm antibiotics, cephalosporins are critically important to humans, too.
MORGAN SCOTT: OK, they’re so critically important because there are certain types of infections for which they’re one of only few choices available to treat these infections. I’ll give you one example. So clinical salmonellosis in children, and in many cases pregnant females, are limited. Some drug classes can’t be used.
DAVID E. HOFFMAN: [on camera] So they’re very valuable for children.
MORGAN SCOTT: They’re very valuable, yes.
DAVID E. HOFFMAN: [voice-over] To try to save cephalosporins for both animals and humans, they designed a novel experiment. The idea was to use more tetracycline, an older drug less important to people, with the hope of reducing resistance to cephalosporin.
[on camera] I see. So you were hoping to essentially play a little bit of a game here, that by using one antibiotic which didn’t have big consequences for human health, you could preserve and protect one that was important for human health.
MORGAN SCOTT: Exactly. Most of the world doesn’t care about tetracycline resistance. They care a lot about cephalosporin resistance.
So obviously, I mean, you’re going to want these, and I’m going to want them, too—
GUY LONERAGAN: And the lid should be there, and the cup, as well.
DAVID E. HOFFMAN: [voice-over] It was cutting edge science, but it started with a plastic spoon.
GUY LONERAGAN: We collected fecal samples directly from the animals. And from those fecal samples, we grew generic E. coli.
We’ll put the samples in the cooler, ready to send.
MORGAN SCOTT: So we’re going to ship these down to College Station to do the microbiology work.
DAVID E. HOFFMAN: When they took their samples to the lab, they got a big surprise.
MORGAN SCOTT: It was, like, “OK, this isn’t going the way we thought it would.”
GUY LONERAGAN: We actually saw that resistance went up, which was not what we hypothesized.
DAVID E. HOFFMAN: Resistance went up to cephalosporins, the drug they were trying to save. And this was what the FDA had been worried about in 1977, that the use of tetracyclines could accelerate the overall spread of antibiotic resistance.
GUY LONERAGAN: Our viewpoint historically has been that, sure, tetracyclines aren’t that important for human health, so why worry about them in animal agriculture. But they may be more important than we think, not because of their use in human medicine, but because they can expand resistance to critically important drugs.
LANCE PRICE, Ph.D., Microbiologist, George Washington Univ.: We did it for an entire year.
DAVID E. HOFFMAN: Back in Flagstaff, Arizona, Lance Price was closing in on his search.
LANCE PRICE: To see whether there’s E. coli in these foods and whether they have drug-resistant bacteria in them.
DAVID E. HOFFMAN: He and his team had spent a year going to supermarkets.
DAVID E. HOFFMAN: [on camera] That’s a lot of chicken.
LANCE PRICE: Yeah, that’s a lot of chicken, turkey and pork.
And this is the micro lab. This is really the heart of our food operation. So we’ll first have you gown up here—
DAVID E. HOFFMAN: At the lab, they’d been testing the meat, looking for traces of dangerous E. coli.
LANCE PRICE: Right. So what they’ve done is they’ve taken, you know, a standard frozen turkey—and these were actually purchased over Thanksgiving—and then culturing the bacteria, the E. coli. When we say that there’s E. coli on a turkey product like this, we want to know that it’s definitely E. coli, and we want to know if it’s the E. coli that can cause bladder infections or kidney infections or blood infections.
DAVID E. HOFFMAN: Twenty percent of the meat they tested had this bad E. coli on it. And a third of that was highly resistant.
LANCE PRICE: OK, so this is an E. coli from the food supply, and it’s resistant to five different antibiotics. So it’s resistant, resistant, resistant, resistant, resistant. So that’s five different antibiotics that a physician can’t use to treat an E. coli infection.
DAVID E. HOFFMAN: [on camera] Wow.
[voice-over] But what Price really wanted to know was whether any of this bacteria had caused those urinary tract infections at the Flagstaff hospital.
HOSPITAL STAFFER: This is where we grow bacteria from patient specimens. This is a person that has gram-negative bacteria.
DAVID E. HOFFMAN: So he got the hospital to send him more than 1,200 samples of urinary tract infections they’d collected from patients.
LANCE PRICE: So this is where we’ve stored all of the samples that we’ve collected from this study, including thousands from the food supply and thousands from urinary tract infections that we collected at the hospital. We have these tubes. And we said, “OK, let’s look at the DNA from the E. coli from the people. Let’s look at the E. coli from the—the DNA from the E. coli in the food supply and say, Are these matched?”
DAVID E. HOFFMAN: By using state-of-the-art whole genome sequencing, he compared the samples he got from the hospital with the bacteria he found on supermarket meat.
LANCE PRICE: So this is all the E. coli we got from the food supply and from urinary tract infections in Flagstaff. So what the computer is doing right now is it’s figuring out how these things are related to one another.
DAVID E. HOFFMAN: Price is only half-way through his study. It has yet to be peer reviewed. But he let us in on his preliminary findings. So far, he says he’s genetically linked more than 100 urinary tract infections back to supermarket meat products, and a quarter of them were resistant to several antibiotics.
For Price, this supported his hypothesis that some of the dangerous urinary tract infections were coming from the food supply.
LANCE PRICE: So here’s evidence that these E. coli, the E. coli in the urinary tract infection, the E. coli in the food, came from the same original E. coli population. So probably the farm.
DAVID E. HOFFMAN: [on camera] Probably the farm. But you don’t really know how it got there, right? That’s a bit of a guess.
LANCE PRICE: When we see this, when we see such genetic relatedness like this, the alternative explanations become, you know, impossible.
DAVID E. HOFFMAN: [voice-over] But even with the high-tech genomics, Price still can’t make all the connections. That’s because he doesn’t have any data on how antibiotics are being used on the farm. I was surprised to find out that farmers aren’t required to report how many antibiotics they’re using, or for what purpose.
[on camera] So we don’t even know how many antibiotics are used on turkeys, as compared to chickens.
CHRISTINE HOANG, D.V.M., Asst. Dir., American Veterinary Medical Assn.: No, we do not.
DAVID E. HOFFMAN: And we don’t even know, really, the volume that’s used for humans, as compared to animals. It’s a guess, right?
Dr. CHRISTINE HOANG: Not really because the data that we have is based on drugs that are being sold, not used or how they’re used.
DAVID E. HOFFMAN: I mean, ideally, what data would you want to know? You’re tracking resistance.
TOM CHILLER, M.D., Associate Director, CDC: I think we’ve been clear for years, all of us—meaning the whole of government, academics, anyone who’s tracking food-borne infections—that we would like use data. To be able to understand resistance and where it’s coming from, it’s going to help a lot for us to have better use data so that we understand how these antibiotics are being used and where they’re being used. I mean, it’s just not available, and it’s not something we collect. And it’s not our area. As was mentioned, you need to talk with FDA.
DAVID E. HOFFMAN: [voice-over] The FDA commissioner is Margaret Hamburg.
[on camera] Why don’t we have that information? I mean, antibiotics have been used on the farm for four, five decades. Why don’t we have it now?
MARGARET HAMBURG, M.D., FDA Commissioner: You know, for me, the question is, Can we get it now? And that’s what we’re working on. I think it’s really—it’s a question of us all working together to identify what are the critical data needs and—
DAVID E. HOFFMAN: Don’t you know that now, though, 40 years? I mean, shouldn’t you have a better handle on that, what data you need?
Dr. MARGARET HAMBURG: Well, you know, you’re asking a very big question in terms of the overall picture. We are focused on certain aspects of this challenge.
DAVID E. HOFFMAN: [voice-over] Last year, there were proposals in Congress that would have required farmers to report in detail which antibiotics they’re using on animals, and how much. But industry groups, like the National Pork Producers Council, opposed those efforts.
[on camera] Did you lobby against those amendments?
LIZ WAGSTROM, D.V.M., National Pork Producers Council: We—those amendments did not have a lot of support among Congress. There was not really a need to actively lobby against them.
DAVID E. HOFFMAN: But you did not want those amendments to be part of that bill.
Dr. LIZ WAGSTROM: We did not think they’d be helpful.
DAVID E. HOFFMAN: What’s to be afraid of with getting more information?
Dr. LIZ WAGSTROM: The people who were asking for that information are people whose motives were to restrict antibiotic use.
DAVID E. HOFFMAN: So you saw this as a way to get a restriction, not just information.
Dr. LIZ WAGSTROM: Correct.
DAVID E. HOFFMAN: [voice-over] The proposals died. And after years of inaction, the FDA tried a new approach last December. It asked the pharmaceutical industry to voluntarily stop selling antibiotics that are intended only to make animals grow faster.
Dr. MARGARET HAMBURG: We actually believe that by taking a voluntary approach, we are going to move towards our goal of getting these antibiotics out of use for growth promotion in a more effective and speedier way than if we actually tried to go drug by drug to pull them from the marketplace.
DAVID E. HOFFMAN: The drug makers agreed to phase out these so-called growth promoters over the next three years, and the FDA will require greater supervision of all antibiotic use by veterinarians.
[on camera] Industry has told us that only 12 percent of the antibiotics that they sell in agriculture are used for growth promotion. So does that really mean that 88 percent of what’s being used today will continue to be used?
Dr. MARGARET HAMBURG: The action we’re taking is one step, but we clearly need a comprehensive strategy in terms of animal health and farm practices, as well.
DAVID E. HOFFMAN: More than is being done today?
Dr. MARGARET HAMBURG: Oh, I think, you know, we view what we’re doing as part of a broader process.
GAIL HANSEN, D.V.M., Pew Charitable Trusts Antibiotic Campaign: I think FDA has—is very cautious. And because of the history that they had in the ‘70s, where they tried this big step and Congress told them no, I think FDA is taking some baby steps. I think they could be much bolder.
LANCE PRICE: I mean, we know what they’re going to do. They’re going to do this voluntary thing, right? But if they’re not collecting the data to verify that people are changing the way they’re using antibiotics, that the program is working, you know, what’s the use? How do we evaluate the success of this program without collecting data?
DAVID E. HOFFMAN: [voice-over] It’s been nearly 40 years since the government first tried to limit the use of antibiotics on farms.
[on camera] Has anything really changed in those 40 years?
TOM GRUMBLY, Fmr. FDA Policy Assistant: Yes, the use of antibiotics has gone up. And certainly, the problem of antibiotic resistance in human beings to drugs has gone up substantially.
GUY LONERAGAN: We live in a shared environment. Bacteria that we can find in animals we can find in people, and bacteria that we find in people we can find in animals. So the route by which they move between them may not be that important, but the fact that they move between the two populations is important.
[Earlier this month, the FDA released new data. From 2009 to 2012, antibiotic sales to farms increased by 16 percent.]
ANNOUNCER: Coming up next on FRONTLINE—
LARRY STULEN, Troy’s Father: You’re watching your son die in front of you, and there’s absolutely nothing you can do.
ANNOUNCER: A drug-resistant superbug shows up in a young patient after NIH doctors thought the outbreak was over.
LARRY STULEN: You’re in the best medical facility in the world. The doctors can do nothing. We can do nothing.
ANNOUNCER: Outbreak at NIH begins right now.
Outbreak at NIH
WRITTEN AND PRODUCED BY
Rick Young & Anthony Szulc
NARRATOR: Nowhere is the threat of antibiotic-resistant bacteria more urgent than in hospitals, with their heavy reliance on antibiotics and their population of vulnerable patients. There have been problems in hospitals around the country, and over the past decade, hospitals in the New York City area have become the epicenter of a particularly resistant and deadly superbug.
It’s called KPC. It lives in the digestive system and can spread its resistance to other bacteria. And patients who get it in one hospital can carry the bacteria to other hospitals.
That happened in a story we first told in 2013, when one of the nation’s most prestigious hospitals, the clinical center at the National Institutes of Health, found itself battling a major KPC outbreak.
It began in the summer of 2011, when a patient with a rare lung disease was transferred from a New York City hospital to be treated at the NIH in Bethesda, Maryland. She was carrying KPC. It was the first case of it the NIH had ever seen.
DAVID HENDERSON, M.D., Dpty. Director, NIH Clinical Center: We immediately went on high alert, the equivalent of hospital epidemiology DEFCON 5, tried to implement as many things as we could think of at the time to prevent any further spread of the organism in the hospital.
TARA PALMORE, M.D., Infectious Disease Specialist, NIH: The patient was placed in what we call enhanced contact isolation, which means everybody who went in the room, including visitors, had to wear gloves and gowns.
NARRATOR: But this was the intensive care unit, where patients are very sick and highly vulnerable.
NURSE: Let me just check the blood sugar, OK?
Dr. DAVID HENDERSON: It’s the kind of place where the bacteria can spread with ease. People are very busy and there are a lot of things going on. Patients get very sick very quickly and require intervention. The bacteria can be spread on the hands. They can be spread on pieces of equipment that might go from patient to patient. So you have to be really cautious.
NARRATOR: Their efforts to contain KPC appeared to work. When other ICU patients were tested for KPC—
Dr. TARA PALMORE: We found nothing. So at that point, we thought that there had not been spread of the bacteria.
NARRATOR: The New York patient ultimately recovered and was discharged after four weeks in the hospital.
Dr. DAVID HENDERSON: We really felt like we had dodged a bullet.
NARRATOR: But then a big surprise.
Dr. TARA PALMORE: Five weeks later, unexpectedly—
ICU NURSE: Could you do me a big favor? Could you get me a—just a tube fixator for—out of the RT closet?
Dr. TARA PALMORE: --KPC bacteria turned up in a respiratory culture—
NARRATOR: And with it, a mystery.
Dr. TARA PALMORE: How this could have spread from the first patient to the second patient.
Dr. DAVID HENDERSON: They were not in ICU at the same time. They didn’t have the same caregivers. They didn’t have the same equipment. So initially, we thought that it might be possible that this was a second introduction of yet another KPC organism.
Dr. TARA PALMORE: I was extremely concerned because the infections with these bacteria had a high mortality rate.
NARRATOR: As they began to investigate, searching for KPC on equipment and testing the patients yet again, they realized the problem was much bigger.
Dr. TARA PALMORE: We started finding other patients in the intensive care unit to whom the bacteria had spread.
NARRATOR: They had an outbreak. The KPC was spreading. The patients were getting sicker. And antibiotics weren’t working.
Dr. TARA PALMORE: And we tried combinations of five, six antibiotics. We tried making oral antibiotics into intravenous antibiotics. We even got an investigational antibiotic from a pharmaceutical company.
DAVID E. HOFFMAN, Correspondent: An experimental one, a test one.
Dr. TARA PALMORE: An experimental antibiotic. And that also did not work.
NARRATOR: Desperate to contain the outbreak, the hospital took unprecedented steps. They created a separate ICU for KPC patients, brought in robots to disinfect empty rooms.
NANCY AMES, R.N., ICU Nurse, NIH: Had monitors here reminding us to wash our hands, built a whole wall up in the other side. We moved every patient in the ICU, completely cleaned it, moved patients back in. And no matter what we did, the bacteria was still—it was still spreading.
Dr. DAVID HENDERSON: We didn’t know what was going on.
NARRATOR: With the hospital in crisis, genetic researchers in building 49 next door were scrambling to figure out how the KPC was spreading.
JULIE SEGRE, Ph.D., Geneticist, NIH: We had now gotten to the point where they were identifying a patient a week, and it was not clear how these patients might be related to each other.
GENETICS RESEARCHER: This bacteria has the capacity to live—
NARRATOR: By comparing the DNA in the KPC samples taken from the patients, the researchers made an alarming discovery, silent carriers, people who were carrying the bacteria but showing no signs of infection, were spreading the KPC.
As they urgently searched for silent carriers throughout the rest of the hospital, their worst nightmare came true. The outbreak had spread beyond the ICU.
JULIE SEGRE: That’s a very scary moment. Suddenly, it’s in the general patient population.
NARRATOR: The staff was in a panic. As they looked on helplessly, patients began to die. There were few options left.
Dr. DAVID HENDERSON: Dr. Gallin asked me if we needed to close the hospital or if we needed to close the hospital to admissions. Ultimately, we decided not to close the hospital, but—
DAVID E. HOFFMAN: It was a possibility.
Dr. DAVID HENDERSON: Absolutely.
NARRATOR: Instead, they expanded testing hospital-wide and isolated all those found with KPC. Finally, six months after patient one first arrived, the outbreak appeared to have ended, almost as suddenly as it had begun.
Dr. TARA PALMORE: We started to be a little more optimistic, and we continued all of our aggressive measures to control the bacteria in the hospital.
NARRATOR: But by then, 18 patients had been infected with KPC and 6 people had died from it.
No patients or their families ever came forward to talk about their experience. But after seeing our story, one family did. Not long after the scare at the NIH subsided, in Willmar, Minnesota, 19-year-old Troy Stulen was recovering from a bone marrow transplant he’d received at NIH months earlier.
LARRY STULEN, Troy’s Father: It went very well. He started recovering. And then one morning, he woke up and he had blisters all over his body. We called the doctors at the NIH, and they were concerned that maybe he would get an infection in these blisters, so they wanted him to come back out there again.
MARILYN STULEN, Troy’s Mother: It was a huge relief to be back there again. I thought of it as being one of the, you know, best of the best hospitals in the nation, and I felt very comfortable being there.
When we got there, he was in a lot of pain, and so they finally gave him some medicine for the pain. But you know, we’re just thinking, “OK, this is just 10 days, you know, short term. You know, they’ll get this figured out, and then we’ll go back home again.” You know, not a big deal.
NARRATOR: Troy had suffered health problems from birth. The most serious was a genetic disorder called chronic granulomatus disease. As he reached his teens, Troy’s illness was causing serious gastrointestinal problems, and his doctors recommended he undergo a difficult and risky bone marrow transplant at NIH.
MARILYN STULEN: And Troy was totally on board about it. He said, “If I have the transplant and I’m cured, I win because I’m healthy and I’m normal. If I die, I win because I go to heaven.”
NARRATOR: Troy’s transplant actually took place at NIH during the KPC outbreak, but he was on another floor and unaffected by it. Now that he was back, his weakened state left him dangerously susceptible to infections. As the days turned into months, his complications worsened.
MARILYN STULEN: As the months progressed, they just couldn’t figure out what to do with his skin. He was in ICU probably four or five times.
LARRY STULEN: It was kind of a balancing act that whole time, you know, how to properly treat him, whether he needed platelets, whether he needed blood, you know, whether he needed more steroids.
MARILYN STULEN: Basically, it got to the point, it was, like, “OK, what’s next?” You know, “What’s the next bad thing that’s going to happen?”
NARRATOR: Then in August 2012, the doctors brought some shocking news. Troy tested positive for KPC. It was eight months after the hospital thought the outbreak was over.
DAVID E. HOFFMAN: When the bacteria came back, did it surprise you?
JULIE SEGRE: That more than surprised me. I mean, that was devastating. It sort of brought back all of the emotions of the fall, the feeling as though we finally have this situation under control, and then a new patient being identified.
MARILYN STULEN: I remember the doctor coming in and saying, “We’ve discovered Troy has KPC,” and said, “We’re going to move him across the hall to the isolation unit.” And I kind of Googled it and stuff like that, and you know, learning that, you know, Hey, this was a pretty serious infection. You know, this was one of those superbugs.
LARRY STULEN: Marilyn just said, you know, “I’m really scared about this infection.”
MARILYN STULEN: He has a low immune system. We’re in a hospital. Yeah, it was very scary. It’s, like, you know, this—we’ve got a lot of things going against us here. But he was doing OK with it, and I’m thinking, “OK, well, maybe—you know, maybe he’ll be fine.”
LARRY STULEN: He had acquired other infections along the way, but they always had antibiotics that were used, and he was able to get through those infections.
NARRATOR: At first, Troy was put on a powerful but toxic antibiotic called colistin, and it appeared to be working.
LARRY STULEN: He was testing negative for the infection and his kidney was working. It seemed like things were heading in the right direction. I was actually heading back home again, and literally, a half hour before I left the hospital, the chaplain and the nurse came and asked Marilyn and I if they could meet with us.
They just said, you know, “You need to start preparing to talk to your son about dying, the possibility of dying.” They said, “We’ve seen this infection before, and it doesn’t always end well.”
And sure enough, you know, a few days later, the doctor said that the infection has mutated and that the colistin is no longer being effective. It wasn’t long after that that his vital signs started to fail. They had exhausted all options, and there was nothing more they could do. All they could do was keep him comfortable at that point.
NARRATOR: On September 7th, 2012, the family gathered in Troy’s room in the ICU.
LARRY STULEN: That was a long day.
MARILYN STULEN: It’s very hard to watch your son, daily, starting to lose his life, and then to see him on a ventilator and not be able to do a thing about it. It’s really hard.
LARRY STULEN: We were able to all be together for the last couple of hours. And Troy passed away that evening about 7:45.
NARRATOR: The doctors said a KPC patient from the earlier outbreak had probably brought the superbug back to the hospital during a routine follow-up. But they were unsure how Troy had come in contact with it.
He was the last victim of the KPC outbreak.
DAVID E. HOFFMAN: Do you think KPC is now gone from your hospital?
Dr. TARA PALMORE: Oh, no. Absolutely not. I think that we have to be extremely vigilant in the coming years. The rate of these infections has risen sharply during the past decade.
NARRATOR: Hospitals are generally not required to report details of outbreaks like this one to the public, but the researchers at NIH believe the lessons are important and must be shared.
JULIE SEGRE: Talking about hospital infections is really difficult for a hospital because we all know that when you come to the hospital, there are certain risks, but we’ve now laid bare what are those risks. We owe it to those patients to honor those patients by ensuring that this does not happen in another hospital.
Dr. DAVID HENDERSON: I guess if I had a major message, it would be that it’s never going to end. This organism and organisms like this are going to be with us. We have to develop new strategies for managing them. We have to change our culture in the hospital.
LARRY STULEN: The surprise to me was that he didn’t die from the bone marrow transplant, which is what—you know, if there was going to be a problem, we thought it would be tied to the bone marrow transplant. We never thought that it would be an infection that couldn’t be cured.