We can take action or lose the drugs we have: Jean Patel regarding antibiotics

THE RISE OFSUPERBUGS

Dangerous infections that are resistant to antibiotics
are spreading and growing stronger, with dire consequences

Published: June 25, 2015

The next time you’re offered a prescription for antibiotics and ask yourself, “What harm could it do?” think about Peggy Lillis. 

Five years ago, the 56-year-old kindergarten teacher from Brooklyn, N.Y., was given the antibiotic clindamycin, which was supposed to prevent a dental infection. Instead, the drug wiped out much of the “good” bacteria in her gut that normally keeps “bad” bacteria in check. Without that protection, harmful bacteria in her belly ran rampant, triggering an intestinal infection so severe that doctors had to perform emergency surgery to remove her colon. Despite that desperate, last-ditch effort, “within 10 days of taking those pills, my mother was dead,” says Lillis’ son, Christian. 

Or consider Zachary Doubek, a rambunctious 12-year-old from New Brunswick, N.J. After a baseball game, Zachary came home complaining of knee pain that worsened overnight and quickly escalated. His doctor initially prescribed an antibiotic that failed to bring the problem under control. Zachary had the bad luck of running into a strain of bacteria that, after repeated exposure to antibiotics, had evolved, developing defenses against the drugs. 

Zachary’s infection raced through his body, forcing doctors to put him in a medically induced coma until they could rein it in with vancomycin, a powerful antibiotic that, luckily, still worked against the germ. Zachary survived, but a year and six surgeries later, he still walks with a limp from the ordeal. “We may never know how he got infected,” says his mother, Marnie Doubek, M.D., a family physician, “but we know that the antibiotic that should have first helped him didn’t work.”

Zachary Doubek with his mother, Marnie Doubek, M.D.

Hear how Zachary Doubek got a life-threatening infection from just playing like a kid.

Scary New Superbugs 

Peggy Lillis’ and Zachary Doubek’s stories are all too common. Though antibiotics have saved millions of lives since penicillin was first prescribed almost 75 years ago, it’s now clear that unrestrained use of the drugs also has unexpected and dangerous consequences, sickening at least 2.25 million Americans each year and killing 37,000.

That harm comes in two main ways. First, as in Lillis’ case, antibiotics can disrupt the body’s natural balance of good and bad bacteria, which research shows is surprisingly important to human health. Lillis was killed by one such bad bug, the bacteria C. difficile. At least 250,000 people per year now develop C. diff infections linked to antibiotic use, and 14,000 die as a result.

Second, overuse of antibiotics breeds “superbugs”—bacteria that often can’t be controlled even with multiple drugs. Doubek was a victim of MRSA (methicillin-resistant staphylococcus aureus), a bacteria once confined to hospitals that has now spread into the community, including nail salons, locker rooms, and playgrounds—where Doubek may have picked up his infection. MRSA and other resistant bacteria infect at least 2 million people in the U.S. annually, killing at least 23,000. (Read more about deadly hospital infections and see our hospital ratings.)

As alarming as those numbers are, experts say things could get much worse, and fast. The Centers for Disease Control and Prevention has sounded the alarm about two threats: CRE (carbapenem-resistant enterobacteriaceae), which—when it gets into the bloodstream—kills almost 50 percent of hospital patients who are infected; and shigella, a highly contagious bacteria that overseas travelers often bring home and that is now resistant to several common antibiotics, raising fears of an outbreak in the U.S.

The World Health Organization and the European Union call the rise of resistant bacteria one of the world’s most serious health crises, putting us on the verge of a “post-antibiotic era.” In June, President Obama convened a forum on the crisis at the White House attended by 150 organizations, including Consumer Reports. And his 2016 proposed budget included $1.2 billion for combatting resistant infections.

More From Consumer Reports

Read the other parts of our series: "Making the World Safe From Superbugs" and "How Your Hospital Can Make You Sick." Plus, check our special report "How Safe Is Your Ground Beef?" and antibiotic resistance guide.

2.25+
Million

Number of people sickened each year by misuse of antibiotics

How Antibiotics Can Kill

Christian Lillis (sitting) and his brother Liam outside their family home in Brooklyn, N.Y., with a picture of their mother Peggy. She died when an antibiotic prescribed after a routine root canal killed off “good” bacteria in her stomach, allowing a “bad” bacteria, C. difficile, to spread throughout her body. The family responded to the tragedy by creating the Peggy Lillis Memorial Foundation.

37K+

people are killed each year by the misuse of antibiotics. Help support our work on eliminating this misuse

Miracle Drugs Gone Awry

“We have to act now to reverse this problem,” says Thomas R. Frieden, M.D., director of the CDC. “If we lose the ability to treat infection, we lose the ability to safely do much of what we take for granted in modern medicine.”

Part of the solution may come from developing new antibiotics. But experts say it’s even more important that doctors, hospitals, and consumers develop a new attitude to the drugs, learning when antibiotics should—and shouldn’t—be used. 

That applies even to how the drugs are employed on farms: 80 percent of the antibiotics in the U.S. are actually fed to chickens, cows, and other food animals, mostly to speed their growth and to prevent disease. 

Frieden and others say the problem, although complex, is fixable—if we act now. Here, what you need to know about antibiotic overuse and its consequences, and how to protect yourself and your family.

“Antibiotics really are miracle drugs. Patients believe that. I believe that,” says Lauri Hicks, D.O., head of the CDC’s program Get Smart: Know When Antibiotics Work.

Ask anyone who has had a brush with bacterial meningitis. About 85 percent of people treated with antibiotics for that infection survive; without the drugs, almost all die. In fact, many of the advances of modern medicine—organ transplants, invasive surgery, cancer therapy, among others—depend on antibiotics. For example, without the drugs up to 40 percent of people undergoing total hip-replacement would develop an infection and almost one-third of those would die. 

But antibiotics have become a victim of their own success. “The drugs seemed so effective that we started using them even in cases when they shouldn’t be,” Hicks says. Overall, in fact, the CDC estimates that up to half of all antibiotics used in this country are prescribed unnecessarily or used inappropriately.

How Doctors Misuse Antibiotics

Antibiotic misuse happens in many ways: 

Using the drugs to treat illnesses caused by viruses, not bacteria. Doctors know, of course, that antibiotics don’t work against viruses, like those that cause the common cold or the flu. But in some cases tests can’t help distinguish between the two. Or doctors may feel that they just don’t have the time to determine the cause, and figure “it’s better to be safe than sorry.” One recent study of 204 doctors suggested some physicians may be more likely to prescribe antibiotics for viral infections toward the end of their office hours—a sign they may be taking the easy route to handling patients’ complaints. 

Prescribing the drugs just to satisfy patient demand. Doctors may also just want to make their patients happy—and patients often want antibiotics. For example, in a recent Consumer Reports poll of 1,000 adults, one in five people who got an antibiotic had asked for the drug. “I often have patients who ask for antibiotics,” says Marnie Doubek, who sees many sick children in her practice. “So I understand the pressure to just say OK. But now, especially with Zachary’s experience, no way.” 

Rushing to drugs too quickly. Even when infections are caused by bacteria, doctors sometimes prescribe antibiotics when it might be wise to wait a few days to see whether mild symptoms clear up on their own. One example: ear infections in children older than 6 months. When mild, those infections often improve untreated. But as many parents know, a crying child can be a powerful motivator to seek a quick fix even if, in the long run, repeated use of antibiotics may be more likely to cause problems than solve them. 

Abusing broad-spectrum drugs. When antibiotics are called for, doctors often reach too quickly for “broad spectrum” ones that attack multiple bacteria types at once. That shotgun approach is not only more likely to breed resistance but also to wipe out protective bacteria. The drug that triggered Lillis’ C. diff infection, clindamycin, is one such drug. 

Those drugs were developed with the thought that “killing as many bugs as you possibly can in every patient” was a good idea, says John Powers, M.D., former lead medical officer of Antimicrobial Drug Development and Resistance Initiatives at the Food and Drug Administration. 

Doctors loved the broad-spectrum antibiotics and, spurred by aggressive marketing from drug companies, began using them for common problems such as ear and sinus infections. Given that widespread use, “it’s hardly a shock that we now have a problem with resistance and C. diff,” Powers says.

The Danger of New Drugs

Many of those broad-spectrum drugs were introduced 30 years ago, when antibiotic development was in its heyday. More than 50 antibiotics were introduced in the 1980s and 1990s. But that once-steady drug pipeline has slowed to a trickle, for several reasons. 

One is that coming up with new classes of antibiotics that target superbugs is proving to be a tough scientific puzzle. Most of the new antibiotics introduced since 2000 have been minor tweaks to existing drugs, not major breakthroughs. 

The other big reason? Money. “Developing antibiotics is not that profitable,” says Henry Chambers, M.D., an infectious disease specialist at the University of California San Francisco School of Medicine. Drug companies would rather focus on medications that many people take for a long time, he explains, because the market, and profit potential, is larger. 

The government is trying to sweeten the economic incentive. In 2012, the FDA began to fast-track certain antibiotics and told drugmakers that patent protection on the drugs would last an additional five years. Since then, 49 new drugs have entered the pipeline’s fast lane and six have been approved. 

The FDA has proposed further streamlining—allowing companies to test drugs using smaller, shorter, or fewer studies—for antibiotics that are meant to treat serious infections in patients with no other options. Legislation now with Congress would also lower the requirements needed to get new antibiotics on the market.

When Big Pharma Pushes Drugs

That approach means the FDA “is willing to accept less safety and efficacy data,” acknowledges Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. But he says that’s a trade-off that many doctors are willing to make.

Still, some researchers and patient advocates worry about fast-tracking drugs. “We absolutely need new antibiotics,” says Lisa McGiffert, director of Consumer Reports’ Safe Patient Project. “But that doesn’t justify lowering the bar on the standards for drug approval. These can be dangerous drugs, so they should be thoroughly tested for safety and efficacy before we unleash them on the public.” 

Perhaps the biggest concern is that even if effective new antibiotics make it to market, they may not provide much long-term help if health care professionals and patients continue to misuse the drugs. And, Chambers says, there may be pressure on doctors to use the drugs widely, despite the growing threat of antibiotic resistance. 

Some pressure may come from drug companies, which have a history of marketing new drugs aggressively, and even illegally. Pfizer agreed to pay $1 billion in 2009 to settle allegations that the company illegally promoted four drugs, including the antibiotic linezolid (Zyvox), which was pushed to treat forms of MRSA for which it was not approved.

See How Antibiotic-Resistant Bacteria Reach You

A person goes to a hospital for care and is infected by bacteria resistant to antibiotics, possibly bringing the infection home when discharged.

A person goes to a doctor or dentist and is prescribed antibiotics. That can breed bacteria resistant to the drug, so it is less likely to work later when needed.

Animals are fed antibiotics, mostly to help them grow faster. That can breed resistant bacteria, which get passed to humans via food or through water and runoff to the enviroment.

The Real Antibiotic Solution

With education and a little prodding, doctors have shown that they can do better.

One study, in the Journal of the American Medical Association, found that doctors who attended a 1-hour session on guidelines for treating common upper-respiratory tract infections and then received feedback on their prescribing habits, cut their use of broad-spectrum antibiotics almost in half. Inappropriate prescriptions for sinus infections and pneumonia were cut by 50 to 75 percent. 

Several medical organizations, such as the American Academy of Family Physicians and the American Academy of Pediatrics, have distributed guidelines on appropriate antibiotic use to their members. In some cases, that advice is incorporated into electronic medical records, so doctors are alerted if they prescribe a drug inappropriately. 

Still, patients play a key role, too, by helping to make sure those drugs are used only when necessary, and by avoiding infections in the first place. Here are a few guidelines to follow: 

5 Big Myths About Antibiotics

Don’t push for antibiotics. If your doctor says you don’t have a bacterial infection, don’t insist. Ask about other treatments that can help you feel better, such as a pain reliever, throat soother, antihistamine, or decongestant. 

Ask whether you can fight it off on your own. If bacteria are the cause but your symptoms are mild, ask about trying to fight off the infection without drugs.

Request targeted drugs. When possible, your doctor should order cultures to identify the bacteria that caused your infection and prescribe a drug that targets that bug. 

Use antibiotic creams sparingly. Even antibiotics applied to the skin can lead to resistant bacteria. So use over-the-counter ointments containing bacitracin and neomycin only if dirt remains after cleaning with soap and water. 

Avoid infections in the first place. That means staying up to date on vaccinations. And it means washing your hands thoroughly and regularly, especially before preparing or eating food, before and after treating a cut or wound, and after using the bathroom, sneezing, coughing, and handling garbage. Plain soap and water is best. Avoid antibacterial hand soaps and cleaners, which may promote resistance. 

What CR Wants

Doctors to stop over-prescribing

Hospitals to clean up their acts

Farmers to stop using needless antibiotics

When to Say No to Antibiotics

An April 2015 Consumer Reports survey of 1,000 adults found that patients are often prescribed antibiotics when these drugs aren’t really necesssary, such as for colds, sinus infections, and before dental or medical procedures. Several major medical organizations, including the American Academy of Family Physicians and the American Academy of Pediatrics, have recently tried to correct the problem by identifying conditions for which antibiotics are often misused, and explaining when the drugs are, and aren’t, needed:

SINUS INFECTIONS

Sinusitis is usually viral. And even when bacteria are the cause, the infections often clear up even if they are not treated in a week or so. 

When to consider antibiotics: If symptoms are severe, don’t improve after 10 days, or get better but then worsen.

RESPIRATORY INFECTIONS

Colds, flu, and most coughs and cases of bronchitis are caused by viruses. Strep throat is bacterial, but only about one-third of sore throats in children are due to strep. If you suspect strep, get tested to find out for sure. 

When to consider antibiotics: If a cough lasts longer than 14 days or a doctor diagnoses a bacterial illness such as strep.

EYE INFECTIONS

Doctors often prescribe antibiotic eyedrops after treating eye diseases, such as macular degeneration, with injections. But antibiotic drops are rarely necessary after such treatments and can irritate your eyes. 

When to consider antibiotics: If you have a bacterial eye infection, marked by redness, swelling, tearing, pus, and vision loss.

EAR INFECTIONS

Most ear infections improve on their own in two to three days even without drugs, especially in children 2 or older. 

When to consider antibiotics: The drugs may be needed right away for babies 6 months or younger with ear pain, children from 6 months to 2 years old with moderate to severe ear pain, and children 2 or older with severe symptoms.

ECZEMA

Antibiotics don’t help relieve skin from itching or redness. Instead, moisturize skin or ask your doctor to recommend a medicated cream or ointment. 

When to consider antibiotics: If there are signs of a bacterial infection, such as bumps or sores full of pus, honey- colored crusting, very red or warm skin, and fever.

PINKEYE

Conjunctivitis usually stems from a virus or an allergy, not bacteria. Even when bacteria are responsible, pinkeye usually goes away by itself within 10 days. 

When to consider antibiotics: If you have bacterial pinkeye plus a weak immune system, or severe or persistent symptoms.

URINARY TRACT INFECTIONS IN OLDER PEOPLE

Usually given when a routine test finds bacteria in their urine. But if they don’t have symptoms, the drugs won’t help. 

When to consider antibiotics: Before certain surgeries or when you experience burning during urination and a strong urge to “go” often.

SINUS INFECTIONS

Sinusitis is usually viral. And even when bacteria are the cause, the infections often clear up even if they are not treated in a week or so. 

When to consider antibiotics: If symptoms are severe, don’t improve after 10 days, or get better but then worsen.

RESPIRATORY INFECTIONS

Colds, flu, and most coughs and cases of bronchitis are caused by viruses. Strep throat is bacterial, but only about one-third of sore throats in children are due to strep. If you suspect strep, get tested to find out for sure. 

When to consider antibiotics: If a cough lasts longer than 14 days or a doctor diagnoses a bacterial illness such as strep.

EYE INFECTIONS

Doctors often prescribe antibiotic eyedrops after treating eye diseases, such as macular degeneration, with injections. But antibiotic drops are rarely necessary after such treatments and can irritate your eyes. 

When to consider antibiotics: If you have a bacterial eye infection, marked by redness, swelling, tearing, pus, and vision loss.

EAR INFECTIONS

Most ear infections improve on their own in two to three days even without drugs, especially in children 2 or older. 

When to consider antibiotics: The drugs may be needed right away for babies 6 months or younger with ear pain, children from 6 months to 2 years old with moderate to severe ear pain, and children 2 or older with severe symptoms.

ECZEMA

Antibiotics don’t help relieve skin from itching or redness. Instead, moisturize skin or ask your doctor to recommend a medicated cream or ointment. 

When to consider antibiotics: If there are signs of a bacterial infection, such as bumps or sores full of pus, honey- colored crusting, very red or warm skin, and fever.

PINKEYE

Conjunctivitis usually stems from a virus or an allergy, not bacteria. Even when bacteria are responsible, pinkeye usually goes away by itself within 10 days. 

When to consider antibiotics: If you have bacterial pinkeye plus a weak immune system, or severe or persistent symptoms.

Read more about when antibiotics are really needed.

 

Support Our Work on Stopping Superbugs

Consumer Reports is an independent, nonprofit organization that works to protect consumers. Your generous donation today allows us to do more work like “America’s Antibiotic Crisis: The Rise of Superbugs.”

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end quote from:

Keywords for both articles:

The Rise of the Superbug

©2005 WGBH Educational Foundation and Vulcan Productions, Inc.

PROGRAM CONNECTION (continued)

weeds have become resistant to herbicides. Similarly, some types of bacteria have responded to the increasing presence of antibiotics by becoming resistant to them. So bacterial infections may once again become life threatening.
This program follows the case of an American teenager and his doctor battling against an antibiotic-resistant bacterial infection. Antibiotic resistance is then placed in a public health context by examining the large-scale fight against antibiotic-resistant tuberculosis infection
in Peru. The program points out that even when treatments are available, the delivery of those treatments presents yet another set of challenges.
This activity examines one process by which strains of antibiotic-resistant bacteria can arise.

BEFORE WATCHING

• What is an antibiotic? What types of diseases
  do they treat? Have you ever taken antibiotics? If so, which kind(s)?
  An antibiotic is a substance that controls the growth of bacteria, either by killing them or inhibiting their ability to reproduce. They are used to treat bacterial infections, such as bacterial pneumonia, staph, and ear infections. Examples include bacitracin, cephradine, ciprofloxacin (cipro), erythromycin, nystatin, penicillin, and tetracycline.
  
• What do you think it means for a disease to be resistant to a drug, such as an antibiotic? List some issues related to treating a disease caused by bacteria that are resistant to antibiotics.
  Issues include: Not being able to control the infection, putting the patient at serious risk; giving resistant bacteria the opportunity to pass their resistance on
  to other bacteria in the patient’s body; and an increased risk of spreading the resistant bacteria to others in the community.
  ©2005 WGBH Educational Foundation and Vulcan Productions, Inc.
  PROCEDURE
  

1. Distribute the student sheet. Have students read about the teen with the antibiotic-resistant infection on the student sheet and answer question 1.
It is helpful to assign this reading prior to class and to review the concept of natural selection.

• How is the emergence of antibiotic-resistant bacteria an example of natural selection?
This question is explained in the answer to student sheet question 11.
• Discuss what our lives would be like if most bacteria adapted to the presence of antibiotics and became resistant to them.
• Ask why antibiotic-resistant bacteria are such a big problem in hospitals.
Hospitals treat sick people. As a result, they have
a larger number and diversity of disease-causing microorganisms than is typically found in the community. Furthermore, hospitals regularly use medicines that kill disease-causing microorganisms, creating an environment that favors microbes resistant to these medicines. Finally, while the skin is an excellent barrier against microorganisms, it is often broken in hospitals—many patients arrive with open wounds, and it is often punctured by needles and cut with medical implements as well.
• Discuss how human behavior helps resistant strains of bacteria arise. Ask why the overuse and misuse of antibiotics is risky, both for those who overuse or misuse them and for the overall health of the public.
2. Have students work individually, in pairs, in teams, or as a class to complete the student sheet.
Students take on the role of epidemiologists, identifying antibiotic-resistant infections and recommending the best course of treatment. To do this, they analyze
continued

AFTER WATCHING

FOR MORE INFORMATION

pbs.org/rxforsurvival

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TEACHER GUIDE

PROCEDURE (continued)

graphs showing the rate of growth of Eva’s bacteria, which were collected at different times during the course of the infection. See the Assessment section for answers to the questions and for key discussion points.
In steps 2–11, students analyze the graphs showing the growth of Eva’s population of bacteria, develop an explanation of how her antibiotic resistance developed, and recommend a treatment strategy. A complete explanation should mention that the graphs show when the bacteria acquired resistance to antibiotics A and C and how the proportion of antibiotic-resistant and non-resistant bacteria change over the six days. Students should recommend that Eva be treated with Antibiotic B. The following explanation summarizes the key points.

• Figure 4 shows that the population of Eva’s bacteria had no initial resistance to Antibiotics A, B, or C. Therefore, she acquired her resistance in the hospital.
  
• Eva became infected with bacteria resistant to Antibiotic A during her visit to the hospital
  on Monday afternoon. Figure 5 shows that the population declines as Antibiotic A kills the susceptible bacteria. But the population of bacteria resistant to Antibiotic A increases in the test tube. By hour nine, their numbers increase dramatically.
  GOING FURTHER
  Have students analyze the provided electrophoresis
  gel photograph and identify the points at which
  Eva’s bacteria acquired antibiotic-resistant genes. The handout entitled Identify the Genes Carrying Antibiotic Resistance steps students through this analysis.
  Bacteria have both chromosomal DNA and plasmids, which are circular units of DNA. Plasmids can become incorporated into the chromosomal DNA or remain
  ASSESSMENT
  Students’ responses to the questions on the student sheet should incorporate the points discussed in the answers (included in this section). In addition, consider the following when assessing student work:
  

• Supported the team by contributing to the discussion, listening to others’ ideas, working together to analyze the graphs, and helping the team develop a consensus.
  
• Understood how data are presented on a graph and interpreted graphs correctly.
  
• Could articulate when the bacteria acquired resistance to antibiotics A and C and how the proportion of antibiotic-resistant and non-resistant bacteria changed over the six days.
  

• Tuesday morning, Eva took the left-over Antibiotic A. This dose killed the remaining bacteria susceptible to Antibiotic A, leaving only a population of bacteria resistant to Antibiotic A. The graph line in Figure 6 shows that, by Tuesday evening, the population
of bacteria was completely unaffected by Antibiotic A.
• Figure 4 shows that, initially, a few bacteria in the population of Eva’s bacteria are resistant to Antibiotic D. Since Eva never takes Antibiotic D, the proportion of these resistant bacteria does not change over the week—they have no particular advantage over the unresistant bacteria. Figures 4–8 show Eva’s Antibiotic D-resistant population is the same each time, increasing only slightly after being grown in a test tube for 24 hours.
• Figures 6 and 7 show Eva’s population of bacteria becoming resistant to Antibiotic C. Since there were
no Antibiotic C-resistant bacteria on Tuesday evening, Eva must have acquired them after visiting the hospital on Tuesday evening. Eva started taking Antibiotic C Thursday. By Saturday, Eva’s bacterial population is mostly Antibiotic C-resistant because nearly all of the Antibiotic C-susceptible bacteria have been killed.
independent. Some genes that confer antibiotic resistance are carried in plasmids. Bacteria in a population can exchange plasmids. This exchange can transfer antibiotic-resistant genes between bacteria, including bacteria of different species. Before beginning this Going Further activity, you may want to review plasmids, restriction enzymes, and
gel electrophoresis.
• Wrote thoughtful responses to student sheet questions and supported conclusions with data presented in the graphs.
• Explained how the development of antibiotic resistant-bacteria illustrates the process of natural selection.
• Correctly recommended that doctors treat Eva with antibiotic B.
• Demonstrated an understanding of how our
use of antibiotics promotes the development of antibiotic resistant-bacteria and that these bacteria pose a serious threat to global health.

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TEACHER GUIDE

ANSWERS TO RISE OF THE SUPERBUGS STUDENT SHEET

1. (a) What might explain why Eva’s infection is not responding to treatment by antibiotics?
Some bacteria may be resistant to the antibiotics.
(b) What information about the infection would you want in order to find a way to treat it?
It would be good to understand what kinds of bacteria are present and whether they are resistant to antibiotics.

3. Explain how the graphs in Figures 1–3 describe the bacterial growth over the 24 hours.
   No antibiotics: The number of bacteria increases quickly.
   Antibiotics and susceptible bacteria: The number of bacteria declines quickly as the antibiotic kills them.
   Antibiotics and some resistant bacteria: First, the number of bacteria falls as the antibiotic kills
   the susceptible bacteria. Then, because the resistant bacteria have been reproducing, a point is reached where the number of susceptible bacteria being killed equals the increase of the resistant ones. As the population of resistant bacteria continues to grow, the curve stops dropping and begins to rise.
   
4. How will Dr. Hincapie use the three standard graphs?
   These standard graphs show the pattern of growth in bacteria whose resistance to antibiotics is already known. Knowing these growth patterns, he can analyze the growth patterns from Eva’s bacteria in order to identify antibiotic-resistant and antibiotic- susceptible bacteria.
   
5. Were antibiotic-resistant bacteria present in the tissue samples taken when Eva first arrived at the hospital on Monday? (Figure 4) How can you tell?
   Yes. The slight rise starting around hour 12 shows that there were a small number of bacteria resistant to Antibiotic D in the population of Eva’s bacteria when she first arrived.
   
6. By Saturday, which antibiotics were the bacteria resistant to?
   Antibiotics A, C, and D.
   
7. At what point did the population of bacteria show resistance to:
   Antibiotic A – When Eva was at the hospital on Monday afternoon, she picked up some bacteria resistant to Antibiotic A. By taking the leftover antibiotics on Tuesday morning, she killed most of the bacteria susceptible to Antibiotic A, allowing those resistant to it to flourish. The population of resistant bacteria increased dramatically over the week.
   Antibiotic B – No bacteria were resistant.
   

Antibiotic C – When she returned to the hospital on Thursday evening.
Antibiotic D – Eva had some bacteria resistant to Antibiotic D even before her accident.

8. Explain the difference in the growth rates of bacteria grown in the presence of Antibiotic A on Monday versus on Tuesday.
   Eva had no bacteria resistant to Antibiotic A on Monday afternoon. (Figure 4) Yet, after her visit to
   the hospital, Eva had acquired some bacteria resistant to Antibiotic A. Figure 5 shows the population of bacteria decreasing at first as the susceptible bacteria die, but then grows as the resistant bacteria increase in number. On Tuesday morning, Eva took some leftover Antibiotic A. Figure 6 shows that, by Tuesday, all
   the surviving bacteria are resistant to Antibiotic A. (Figures 7 and 8)
   
9. Explain the difference in growth rate of the bacteria resistant to Antibiotic C from Thursday to Saturday.
   As of Tuesday, Eva has no bacteria resistant to Antibiotic C. However, Figure 7 shows that on Thursday, there are a few bacteria resistant to Antibiotic C—Eva must have picked some up when she visited the hospital on Tuesday. Figure 7 shows the population decreasing until hour 20, indicating that most bacteria are still susceptible to Antibiotic C. However, Figure 8 shows that by Saturday the proportion of Antibiotic C-resistant bacteria has increased. Since Thursday evening, Antibiotic C has killed most susceptible bacteria. Figure 8 shows the bacterial population decreasing at first,
   as the remaining susceptible bacteria are killed. Then the number of Antibiotic C-resistant bacteria increases rapidly.
   
10. How is the growth of the bacteria resistant to Antibiotics A, C, and D an example of natural selection?
    Environmental conditions determine which individuals in a population are the fittest. In this case, the environment favored bacteria that were resistant
    to Antibiotics A, C, and D; all others were killed.
    Since only resistant bacteria continued to breed, soon the entire population derived from these initial bacteria and were resistant. Thus, the environment selected for resistant bacteria, illustrating the process of natural selection.
    
11. What advice about the next antibiotic to try can Dr. Hincapie give to Eva’s doctors based on these results?
    Treat Eva with Antibiotic B.
    

4

TEACHER GUIDE

RESOURCES

RELATED RX FOR SURVIVAL WEB SITE FEATURES
(see pbs.org/rxforsurvival)
Why Global Health Matters: Learn why we should all be involved in global health initiatives.
Deadly Diseases: Learn about some of the diseases that are humanity’s most feared killers.
Global Health Champions: Learn about men and women who have profoundly changed global health outcomes and saved lives in many parts of the world.
Get Involved: Find meaningful ways to take action. Dispatches from the Field: Hear first-person accounts
from people on the frontlines of health care.
LINKS
Alliance for the Prudent Use of Antibiotics
tufts.edu/med/apua
Learn about the efforts to promote the responsible use of antibiotics at home and abroad.
Antibiotics: The Untold Story
prairiepublic.org/features/healthworks/antibiotics/ index.htm
Examine our dependence on antibiotics as the most common treatment for illness.
Evolving Ideas: Why Does Evolution Matter Now?
pbs.org/wgbh/evolution/library/11/2/e_s_6.html
Relates how evolving bacterial resistance helps us understand disease treatment and prevention.
Evolution of Antibiotic Resistance
pbs.org/wgbh/evolution/library/10/4/l_104_03.html
See resistant bacteria survive, divide, and multiply in this animated NOVA feature.
National Library of Medicine
nlm.nih.gov/medlineplus/antibiotics.html
The NLM’s Antibiotics page contains detailed information and recent articles on antibiotics.

BOOKS
Antibiotics: Actions, Origins, Resistance Christopher Walsh. Cambridge: Harvard University Press, 2003.
Describes how antibiotics combat infection and disease at the molecular level.
The Coming Plague: Newly Emerging Diseases
In a World Out of Balance Laurie Garrett. New York: Farrar, Straus & Giroux, 1994.
Tracks diseases that travel the world, which are spreading faster and farther than ever before.
The Other End of the Microscope: The Bacteria Tell Their Own Story Elmer Koneman. Washington, DC: American Society for Microbiology Press, 2002.
Tells the story of some bacteria upset at their continued mistreatment at the hands of humans.
Revenge Of The Microbes: How Bacterial Resistance is Undermining the Antibiotic Miracle Abigail A. Salyers, Dixie D. Whitt. Washington, DC: American Society for Microbiology Press, 2005.
Details the consequences of turning one of our best weapons against disease into a powerful enemy.
Infections and Inequalities: The Modern Plagues Paul Farmer. Berkeley: University of California Press, 2001.
Examines how economic disparities are often indicators of who will be treated and survive.
©2005 WGBH Educational Foundation and Vulcan Productions, Inc.

Rx for Survival—A Global Health ChallengeTM is a Co-Production of the WGBH/NOVA Science Unit and Vulcan Productions, Inc. Produced in association with Johns Hopkins Bloomberg School of Public Health. TM/© WGBH Educational Foundation and Vulcan Productions, Inc. All third party trademarks are owned by their respective owners and used with permission. Major funding for Rx for Survival—A Global Health Challenge is provided by the Bill & Melinda Gates Foundation and The Merck Company Foundation.

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TEACHER GUIDE

Rise of the Superbugs

Stephen Schudlich ©WGBH Educational Foundation

On Monday, Eva went to the emergency room following a fall from her bike. Fortunately, her only broken bone was a finger. But she suffered scrapes and cuts, including some deep cuts on her legs. After spending several hours in the emergency room having her wounds cleaned, stitched, and bandaged, Eva returned home.
Tuesday morning, one of the deeper cuts on Eva’s legs was red and felt warm. She had a few pills of an antibiotic left over from her bout with strep throat that previous winter. Thinking it might help to prevent infection, she took them according to the prescription instructions.
Throughout Tuesday, the cut on Eva’s leg became increasingly red, swollen, and painful. Eva felt awful and returned to the hospital on Tuesday night. Her cut had become infected. The doctors cleaned and restitched her leg and prescribed a daily dose of Antibiotic A, a stronger version of the same antibiotic Eva had taken at home just that morning.

By Thursday, Eva’s infection had spread to the point where it was too painful to walk. In addition, Eva felt ill. She returned to the hospital and this time was admitted. The doctors immediately administered a different kind of antibiotic, Antibiotic C, directly into Eva’s bloodstream through an intravenous tube.
Friday, Eva felt better, and her leg became less painful and swollen. But on Saturday, it was clear that Eva had taken a turn for the worse. The infection on her leg continued to spread, and she had become feverish. The medical staff involved with Eva’s case held a meeting to plan the next steps in Eva’s treatment.

1. Answer the following questions:

1. (a)  What might explain why Eva’s infection is not responding to treatment by antibiotics?
   
2. (b)  What information about the infection would you want in order to find a way to treat it?
   

DID YOU KNOW?

Streptococci, the bacteria that cause sore throats and tonsillitis, are usually present in the body. These bacteria cause no harm until the immune system is weakened in some way, such as by a virus or malnutrition.

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STUDENT SHEET

©2005 WGBH Educational Foundation and Vulcan Productions, Inc.

2. Read the following story about a doctor who tested the bacteria causing Eva’s infection.
Dr. Hincapie, a conscientious intern interested in sports injuries, had followed Eva’s case since she arrived
at the emergency room after her bike crash on Monday. On each visit, he had taken samples of fluid and tissue from Eva’s wounds. He wanted to analyze them to see how the cells in her immune system changed
as she healed.
As Eva’s condition worsened, he realized that the samples he had collected might hold clues as to why her infection was not healing and what new treatments might work. Dr. Hincapie thought that bacteria that were resistant to the antibiotics she had been given might be causing Eva’s worsening condition. To test this idea, he grew cultures of bacteria from each of Eva’s visits. (FIGURES 4–8) Dr. Hincapie compared the resulting graphs to standard graphs. (FIGURES 1–3) To make a standard graph, researchers grow 10,000 (104) bacteria in a test tube under known conditions. They measure the growth over 24 hours and graph the results. The standard graphs Dr. Hincapie used in his comparisons are:

1010 1010 1010 108 108 108 106 106 106 104 104 104 102 102 102
000

0 6 12 18 24
FIGURE 1. No antibiotics.
The test tube contains bacterial- growth media, which allows
the bacteria used in testing to undergo unlimited growth.

0 6 12 18 24
FIGURE 2. Antibiotics and susceptible bacteria. The test tube contains bacterial growth media and antibiotics known to kill the bacteria used in the test.

0 6 12 18 24
FIGURE 3. Antibiotics and
a population with some resistant bacteria. The test tube contains bacterial growth media and antibiotics to which some of the bacteria are resistant.

In any population, the individuals are not identical to each other—just look around the classroom! There
is always variation in a population. In bacteria, this includes variation in resistance to antibiotics. Some bacteria may be resistant to antibiotics while others are susceptible. While antibiotics kill most bacteria, some will be resistant and survive. Because the conditions determine which individuals in a population are the most fit to survive, this is an example of natural selection.

3. Explain how the graphs lines in FIGURES 1–3 show how the number of bacteria changes over the 24 hours. No antibiotics:
   Antibiotics and susceptible bacteria:
   Antibiotics and some resistant bacteria:
   
4. How will Dr. Hincapie use the three standard graphs?
   

DID YOU KNOW?

Scottish researcher Alexander Fleming accidentally discovered penicillin in 1928. He observed that a mold growing on one of his Petri dishes had killed all the bacteria growing nearby.

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STUDENT SHEET

Using the standard graphs (FIGURES 1–3), Dr. Hincapie can now analyze the results of the bacterial cultures he grew from Eva’s tissues over the course of her infec- tion. Examine FIGURES 4–8, and answer questions 5–11.
5. Were antibiotic-resistant bacteria present in the tissue samples taken when Eva first arrived at the hospital on Monday? (FIGURE 4) How can you tell?

1010 108 106 104 102
0
1010 108 106 104

Antibiotic A
Antibiotic B Antibiotic C Antibiotic D
12 18 24

FIGURE 4.
Monday afternoon after arriving at the hospital, before any antibiotics were taken.
FIGURE 5.
Monday evening just before leaving the hospital, before any antibiotics were taken.
FIGURE 6.
Tuesday night after returning to the hospital. Eva had taken Antibiotic A. The doctors prescribed a new dose of Antibiotic A.
FIGURE 7.
Thursday evening after returning to the hospital
a second time and being admitted. Eva had taken Antibiotic A since Tuesday morning. The doctors prescribed Antibiotic C.
FIGURE 8.
Saturday morning after spending Friday in the hospital and taking Antibiotic A since Tuesday and Antibiotic C since Thursday night.

0 6

6. By Saturday, which antibiotics were the bacteria
resistant to? 102

0
1010 108 106 104 102
0
1010 108 106 104 102
0
1010 108 106 104 102
0

0 6

12 18 24

7. At what point did the population of bacteria show resistance to:
   Antibiotic A:
   Antibiotic B:
   Antibiotic C:
   Antibiotic D:
   
8. Explain why the number of bacteria is so different
   on Monday afternoon (FIGURE 4) compared to Tuesday (FIGURE 6), after growing for 24 hours in the presence of Antibiotic A.
   
9. Explain why the number of bacteria is so different on Thursday (FIGURE 7) compared to Saturday (FIGURE 8), after growing for 24 hours in the presence of Antibiotic C.
   

0 6

12 18 24

0 6

12 18 24

0 6

12 18 24

KEY FOR THE RESPONSE TO FOUR ANTIBIOTICS
Each sample begins with 10,000 (104) bacteria. Hour zero represents the bacteria in Eva’s blood at the time mentioned in the caption of each figure. The following 24 hours represent the growth occurring in Dr. Hincapie’s test tubes. To understand whether or not Eva’s bacteria are resistant, see how the population changes over 24 hours.

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STUDENT SHEET

10. How is the growth of the bacteria resistant to Antibiotics A, C, and D an example of natural selection?

11. Based on the results of his testing, what advice should Dr. Hincapie give to Eva’s doctors about the next antibiotic to try?
GOING FURTHER: Identify the Genes Carrying Antibiotic Resistance
In bacteria, the genes for antibiotic resistance are often carried on plasmids (small circles of DNA) rather than in the main bacterial chromosomal DNA. Plasmid DNA can be prepared and viewed using gel electrophoresis.
Dr. Hincapie wanted to determine which gene was responsible for the antibiotic resistance he observed in the bacteria causing Eva’s infection. First, he isolated plasmid DNA from each of Eva’s original samples. Then, he separated the plasmid DNA samples using gel electrophoresis. Here’s a photograph of his gel.
WELL NUMBER WELL 123456 NUMBERSAMPLE

DID YOU KNOW?

Some bacteria exchange genetic material using a tiny tube that connects them together. In this way, a drug- resistant bacterium can pass its resistance on to others.

1 2 3 4 5 6

DNA size marker
Monday, immediately after arriving at the hospital Monday evening, just before leaving the hospital Tuesday night after returning to the hospital
Thursday evening, after being admitted to the hospital Saturday morning

2100 bp
1800 bp 1500 bp
1200 bp
1000 bp 900 bp 800 bp
700 bp
600 bp 517/500 bp
300 bp

Dr. Hincapie recognized that the two larger pieces of DNA— 2100 base pairs and 1800 base pairs—were from plasmids found in bacteria that cause infections. The brightness of a piece of DNA on a gel reveals two things: larger pieces of DNA are brighter than smaller pieces and larger amounts of DNA appear brighter than smaller amounts. Knowing this, which bands on this gel do you think contain a gene for resistance to:
Antibiotic A: Antibiotic B: Antibiotic C: Antibiotic D:
Rx for Survival—A Global Health ChallengeTM is a Co-Production of the WGBH/NOVA Science Unit and Vulcan Productions, Inc. Produced in association with Johns Hopkins Bloomberg School of Public Health. TM/© WGBH Educational Foundation and Vulcan Productions, Inc. All third party trademarks are owned by their respective owners and used with permission. Major funding for
Rx for Survival—A Global Health Challenge is provided by the Bill & Melinda Gates Foundation and The Merck Company Foundation.

RISE OF THE SUPERBUGS 

I first heard about this years ago and knew that eventually what is happening with Antibiotics likely could easily kill all mankind as the superbugs get worse from adaptation to antibiotics. So, at a certain point superbugs are going to kill everyone. So, the Russian work with phages always seemed like a more sane idea to me because it was always just a matter of time before we killed everyone and everything using Antibiotics. The same thing is true of pesticides and herbicides where you only breed tougher and tougher bugs and eventually kill everyone from this process. It's a logical no brainer so I don't understand why people have put up with this insanity so long?