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Chapter 6
Challenge of Antimicrobial Resistance: MRSA and More
Introduction
Since the first sulfa drugs became available in the 1930’s, antimicrobial drugs have been hailed as miracle drugs that have saved millions of lives. However, with each passing decade more bacteria have become resistant to either single antibiotics or multiple antibiotics making some diseases more difficult to control. Most clinically important bacteria, viruses and protozoan have now developed strains that are resistant to some antimicrobials. Increased antimicrobial resistance can lead to more visits to the doctor, more hospitalizations, lengthier illnesses and more deaths.
Addressing the challenge of antimicrobial resistance requires a partnership between prescribers, patients, hospitals, pharmaceutical companies, government agencies, and livestock feeding operations.
In this chapter we will explore the development of antibiotic resistance strains of Staphylococcus aureus , called MRSA, and investigate the extent of the problem. We will then explore other examples of antibiotic resistance and examine how surveillance of antibiotic resistant bacteria can be used to develop criteria for prudent use of antibiotics. We will then investigate how physicians, consumers and policy makers might reduce the incidence of antibiotic resistant infections.
Investigation 1: MRSA on campus
The coach of the football team from your college has suddenly become obsessively clean, insisting that everyone showers after practice, that no one shares towels, and that all scraped shins are cleaned and bandaged as soon as possible. (Figure
6-1) When asked by the student newspaper why he suddenly changed his behavior, he replied that one of the teams in the conference had several students who had developed skin infections that tested positive for
MRSA, and one athlete
Figure 6-1. MRSA education poster was hospitalized with necrotizing fasciitis. He didn’t want any of that for his team.
1.
In a small group, discuss and complete Table 6-1 listing “What” you already know about MRSA, and “What” you need to know.

Table 6-1. What do I Know? What do I need to know?
What Do I Know?
What Do I Need to Know?
2.
The coach in the introductory story was concerned about MRSA spreading through his team. Develop a one-page brochure to explain to athletes why their attention to good hygiene is important in the locker room and the weight room.
The brochure should briefly describe what MRSA infections are and what they look like. Prevention details should address personal hygiene, sharing personal items such as towels, and care of scratches and wounds.
Resources for investigation:
Video about MRSA in high schools http://www.youtube.com/watch?v=GrySW5FeCmU
MRSA among athletes http://www.cdc.gov/ncidod/dhqp/ar_MRSA_AthletesFAQ.html
Case on USC football team http://www.aaos.org/news/bulletin/oct07/clinical1.asp
Living with MRSA http://www.tpchd.org/files/library/463bf2a956f3d453.pdf
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Biology of MRSA
Methicillin-resistant Staphylococcus aureus , MRSA (pronounced mersa ), are a group of staphylococcal strains that are resistant to methicillin and other related antibiotics such as penicillin, oxacillin and cephalosporins. These resistance traits make these normally treatable bacteria hard to kill and make infections potentially deadly. S. aureus is a sphereshaped, gram-positive bacterium which is part of the normal microbiota of the skin and nasal passages.
(Figure 6-2) Most “staph” infections are not caused by
MRSA and non-MRSA strains are usually easier to treat than infections caused by MRSA.
One study estimates that there were 94,360 hospitalizations for invasive MRSA infections in the
US in 2005, and 18,650 hospital deaths due to these infections. (Klevens, 2007) About 85% of these infections were associated with healthcare and 14%
Figure 6-2. S. aureus bacteria escaping destruction by human white blood cells. (Credit:
NIAID/RML) were associated with the community. In the U.S., hospital-acquired MRSA (HA-
MRSA) infections have been a problem since the 1960’s and made up 64.4% of the infections caused by S. aureus in intensive care units (Klevens, 2006). Communityacquired MRSA (CA-MRSA) infections started emerging in the late 1990’s. The failure of antibiotics to treat common bacterial infections like S. aureus has led physicians to worry about the potential end of the era of antibiotics and the need to resort to older and more toxic drugs. (Arias and Murray, 2009)
When penicillin was first produced, strains of S. aureus were sensitive to the antibiotic. However, a plasmid-borne gene for penicillin resistance has made some strains of Staphylococcus resistant to penicillin. (Read on to learn more about plasmids and antibiotic resistance genes.) Semi-synthetic versions of penicillin such as methicillin were introduced to circumvent resistance but bacteria developed resistance for those antibiotics as well. Methicillin is no longer used in the United
States and the term “MRSA” has come to mean strains of
S. aureus that are resistant to many antibiotics related to penicillin and methicillin.
In 2004 approximately 29% of the U.S. population silently carried non-
MRSA S. aureus while 1.5% silently carried MRSA. (Gorwitz, 2007) Physicians and microbiologists say that these people were “colonized” by the bacteria. Infections occur when these bacteria bypass the barriers of the immune system and enter the body through cuts and scrapes where they are able to multiply and produce toxins.
Investigation 2: How do HA-MRSA strains differ from CA-MRSA strains?
The location and severity of infections caused by CA-MRSA and HA-
MRSA differ. In general the community associated infections are less severe and respond better to treatment because they are susceptible to a number of antibiotics which can be used to treat the infection. CA-MRSA infections often occur in different tissues than HA-MRSA strains. Figure 6-3 shows the

4 predominant sites infected by CA-MRSA. HA-MRSA strains are resistant to many antibiotics and colonize more invasive sites making them more difficult to treat. The spectrum of disease caused by HA-MRSA infections in hospitalized patients is shown in Fig. 6.4.
Figure 6-3. Locations and percentages of CA-MRSA infections
Figure 6-4. Locations and percentages of HA-MRSA infections

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1.
Contrast the infection site locations for HA-MSRA and CA-
MRSA. List two observations and suggest an explanation for each trend. Use Internet sources to help explain the trends.
The location frequencies for infection sites for CA-MRSA and
HA-MRSA are totally different. The most frequent site for CA-
MRSA is skin/soft tissue while for HA-MRSA it is bacteremia.
Skin/soft tissue infections occurred 76% of the time with CA-
MRSA infections and only 9.7% (cellulitis) with HA-MRSA.
Bacteremia occurred 2.6% of the time with CA-MRSA infections and 75.2% with HA-MRSA. Patients in hospitals undergo various procedures such as venapuncture and surgery expose them to possible infections of other tissues besides skin. They also have underlying health conditions that may lower their resistance.
2.
The CDC provides educational materials about MRSA for healthcare professionals. Explore this CDC site and linked pages to learn more about MRSA, taking a look at the photos of infections, reading about HA-MRSA and CA-MRAS, and checking out the links on “Prevention.” Read the algorithm for treatment of CA-MRSA and eradication of MRSA colonization in individuals who have become carriers. Complete Table 6-2.
Resources for investigation:
CDC MRSA site http://www.cdc.gov/mrsa/mrsa_initiative/skin_infection/
Algorithm for treating MRSA http://www.tpchd.org/files/library/37cdc74cac9cb379.pdf
Table 6-2. Characteristics of CA-MRSA and HA-MRSA strains
Characteristic
Type of infections
At-risk populations
Patient’s under-lying conditions
Age group
CA-MRSA skin infections: abscesses, boils, and other pus-filled lesions
& groups such as athletes, military, prisoners
None
Younger
HA-MRSA
Pneumonia, septicemia, urinary tract, wounds
Associated with outbreaks in health care facilities
Health-care related procedures: incisions, catheters, dialysis
Older

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Antimicrobial resistance
PVL: cytotoxin produced by bacteria that kills white blood cells, monocytes and macrophages; increases
Susceptible to multiple antibiotics
Many strains
Resistant to multiple antibiotics
Few strains virulence of bacteria
Prevalent genotypes (U.S.) USA300, USA400 USA100, USA200
Investigation 3: Transmission and epidemiology of MRSA
The first steps to designing a program to lower the incidence of the disease are to understand how the pathogen causes disease, learn how it is transmitted, and conduct epidemiological studies. Epidemiology is the study of the distribution and incidence of a disease using surveillance data and other data sets as appropriate. In this investigation we will use data sets to better understand transmission patterns. We will begin with an example of a hospital infection-control team gathering data to track down the source of an outbreak of MRSA.
Between May-December a large hospital in Chicago reported a cluster of MRSA skin infections in babies born in the nursery and in most cases sent home. The average age of the babies was 7 days. (MMWR, 2006) Ten infants received topical antibiotics and three of those infants also received oral antibiotics. The 11 th infant was hospitalized for the infection and received antibiotics; all the infants recovered. There was no indication that family members of the infants had skin infections that were caused by
MRSA. Nasal cultures were taken from 135 healthcare workers (HCW) from the labor and delivery, postnatal, and newborn nursery wards. Two HCW, a physician and a nurse, were found to be colonized with the same strain of
MRSA that was isolated from 6 infants who were cultured. The strain was a
USA300, typical of CA-MRSA, and had previously been isolated from nursery outbreaks in Los Angeles and New York. In-service training was held for the wards listed above and the two colonized individuals were treated with intranasal mupirocin, an antibiotic, to clear the MRSA from their nostrils.
1.
One of the challenges in tracking down the source of the infection is that there are time, money and practical limitations on the amount of testing that can be completed. With these limitations, the investigator tries to put the pieces of the puzzle together. a.
How do you think this outbreak started? Generate two possible explanations.

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MRSA could have been introduced to the nursery by a family member who was colonized with MRSA but did not have an active infection. The MRSA could have been transferred from one baby to another during routine baby care. The healthcare workers could have been colonized from the infected babies.
Colonized, non-symptomatic healthcare workers could have introduced MRSA to the nursery and it could have spread among the babies during routine care. b.
In an ideal world what data would you collect to confirm the source of the infection? Explain.
Ideally it would have been good to culture all the family members that were in contact with the babies to see if they were colonized.
Also, taking histories of the culture-positive healthcare workers and family members might have helped with developing a timeline.
The Biology of Antibiotic Resistance
The development of antibiotics in the
1930s and 1940s dramatically changed healthcare around the world. Bacterial infections that had been deadly were suddenly curable. Childhood ear infections didn’t progress to cause deafness.
Sexually transmitted infections like gonorrhea and syphilis were curable. Sulfa drugs, introduced in
1932, were widely used by the Allied Forces in
WWII. By 1941 penicillin was being produced in large-scale batches and was used during the war to treat infections. (Figure 6-5)
Figure 6-5. U.S.
Department of Health &
Services
Antibiotics are naturally occurring or synthetically produced chemicals that can kill bacteria by interrupting their metabolism and reproduction. Antibiotics work by targeting metabolic functions that differ between bacterial cells and eukaryotic (nucleus containing; make up human tissue) cells, allowing them to harm bacteria without harming the host.
As the medical world was marveling at the success of these drugs, few predicted the evolution of antibiotic resistant strains and the struggle to develop new drugs to avoid the resistance. However, by 1944 the first penicillin resistant strains appeared in hospitals and after six years they made up 25% of the Staphylococcus aureus hospital isolates.
(Figure 6-6) These resistant strains produced an enzyme, called penicillinase, which inactivated penicillin.
Figure 6-6.
Increase in the prevalence of penicillinase-producing, methicillinsusceptible strains of Staphylococcus aureus in hospitals (closed symbols) and the community (open symbols). (Chambers, 2001)

Antibiotic resistance is the ability of bacterial strains to grow in the presence of an antibiotic. In a large population of bacteria, a few cells may become resistant to the antibiotic and through natural selection those bacterial types survive and reproduce to become the predominant organisms in the population. (Figure 6-7)
Figure 6-7. Development of antibiotic resistance in bacteria. (Jones & Bartlett,
Pommerville, Alcamo's Fundamentals of Microbiology, 8th Edition, Figure 24.14)
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Antibiotic resistance may develop in a bacterial cell due to a mutation in its
DNA that changes one of the targets of the antibiotic or gives the cell the ability to destroy, inactivate or pump out the antibiotic. Since the changes are in the DNA, the new traits can then be passed on to other cells. Sometimes the antibiotic resistant genes in bacteria are carried on small, circular pieces of DNA called plasmids.
Plasmids are independent of the bacterial chromosome and can replicate. Antibiotic resistance genes carried on plasmids can spread resistance to bacteria of the same or different species. Figure 6-8 shows other ways that bacteria transfer genetic material to other cells.

Figure 6-8. Bacterial gene transfer can be vertical or horizontal
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Investigation 4: Antibiotic resistance affects treatment options
Look at the tutorial, Antibiotics attack, on the Howard Hughes
Medical Institute site and focus on the “Antibiotic resistance” section to learn more about how resistance is spread between organisms. Explore the related material in the online textbook site. Next watch “Super Bugs-Bacterial
Resistance” on YouTube.
1.
In the video, “Super Bugs-Bacterial Resistance,” Steptococcus pneumoniae (pneumococcus) was used as an example of a bacterial species with strains that had developed resistance to several antibiotics. The CDC reports that 38% of the isolates for this organism, which causes a type of pneumonia, a type of meningitis and some ear infections, are resistant to at least one antibiotic. In late 2000 a vaccine for pneumococcus was approved by the FDA for use in children and is included in the standard US immunization schedule. Since the introduction of this vaccine, the incidence of antibiotic-resistant strains of S. pneumoniae has declined. How would you explain this decrease in antibioticresistant strains?

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There was a decrease in the number of cases of disease caused by
Streptococcus pneumoniae after the vaccine was introduced. With fewer cases, fewer antibiotics were prescribed for the organism and resistant strains were less likely to develop.
2.
Patients being treated for tuberculosis may be prescribed as many as four antibiotics at the same time, e.g. rifampin, ethambutol, isoniazid, and pyrazinamide. In addition, patients are observed taking their medications under a program called “directly observed treatment” (DOT) to insure that the treatment plan is followed. Why is this strategy used?
If patients are treated with multiple drugs there is less likelihood of resistant strains developing. If the organism develops resistance to one antibiotic, the other antibiotics will still be active and kill the strain. Using antibiotics with different modes of action helps prevent resistant strains from developing, too. It is important to maintain even drug levels in the body.
Resources for investigation:
Howard Hughes Medical Institute http://www.hhmi.org/biointeractive/Antibiotics_Attack/frameset.html
Online textbook http://textbookofbacteriology.net/resantimicrobial.html
Super Bugs-Bacterial Resistance http://www.youtube.com/watch?v=VQhIz2LqrYA&feature=channel_ page
Treatment of Tuberulosis http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm#tab3
3.
Antibiotic resistance has evolved in many different types of pathogens besides Staphylococcus aureus . Choose a disease agent from the list in Table 6.5 and prepare a description of the organism, the symptoms of the condition that it causes and the consequences of antibiotic resistance. If possible, identify the resistance strategies used by the pathogen. Use the resources of the Centers for Disease Control, World Health Organization and other web sources.
Students should write one to two pages on the organism that they choose describing the diseases it causes, the antibiotic treatments

11 that are used, the development of antibiotic resistant strains and the challenges faced in treating the disease.
Resources for investigation:
Diseases connected to antibiotic resistance http://www.cdc.gov/drugresistance/diseases.htm
Publications on antibiotic resistance http://www.cdc.gov/drugresistance/publications.htm
Table 6.5. Examples of pathogens that have developed antibiotic resistant strains.
Organism
Enterococcus
Streptococcus pneumoniae
Clinical Infection
Urinary tract infections, bacteremia, bacterial endocarditis, diverticulitis, and meningitis
Pneumonia, bacteremia, otitis media, meningitis, sinusitis,
Streptococcus pyogenese
Pseudomonas aeruginosa
Clostridium difficile
Escherichia coli
Staphylococcus aureus
Mycobacterium tuberculosis
Plasmodium sp.
(protozoan)
Trypanosoma brucei rhodesiense and Trypanosomoa brucei gambiense
Skin infections, cellulitis, impetigo
Opportunistic infections, skin infections
Diarrheal disease
Bladder infections, GI tract infections
Skin infections, pneumonia, sepsis
TB
Malaria
Sleeping sickness
4.
Resistance vs. Virulence: The news media often refer to antibiotic resistance occurring in a strain of bacteria and then proceed to refer to the organism as being virulent. Resistance and virulence are two different characteristics of bacteria. Virulence factors are responsible for aiding bacteria to invade the host tissue and establish themselves as pathogens. They are either enzymes secreted by the bacteria or toxins produced by the bacteria.
Staphylococcus sp. produces a number of virulence factors which vary from strain to strain. One factor, Panton-Valentine
Leukocidin (PVL), is produced by many CA-MRSA strains but not the HA-MRSA strains. PVL is a cytotoxin that kills white

12 blood cells, monocytes and macrophages by forming holes in the cell membranes. How does the activity of PVL make the bacteria more invasive? Does PVL affect the antibiotic resistance of
Staphylococcus ?
PVL is a toxin that causes holes to form in the cell membrane of white blood cells, monocytes and macrophages at the site of the infection. Damaging the immune defense cells gives the bacteria more time to establish themselves as pathogens. It does not affect the antimicrobial resistance of the organism.
Resources for investigation:
PVL activity http://en.wikipedia.org/wiki/Panton-Valentine_leukocidin
Invasive factors http://textbookofbacteriology.net/colonization_3.html
Biofilm Formation Increases Resistance to Antibiotics
Bacteria are most often thought of as single cells, or small chains or clusters of cells that act independently and do not need to be attached to a surface to express their genes. Over the last 20 years scientists have learned that bacteria in many environments are not free-floating and independent, referred to as planktonic bacteria, but are actually organized into layers growing on surfaces. These organized communities, called biofilms, are found in the soil, fresh and salt water, foods, manufacturing plants, the cow’s rumen, the human body and many other places.
The biofilms begins to form when planktonic bacteria attach to a surface and establish themselves. The attachment triggers physiological changes that stimulate the cells to grow, divide and secrete a complex mixture of polysaccharides, DNA and proteins that make up the “slime” layer that we call biofilms. Cells are able to release signaling molecules to chemically communicate with each other and detect conditions such as cell density or the presence of antibiotics. This signaling, called quorum sensing, enables the group of individual cells to coordinate their response to the environment. The process of biofilm formation is shown Fig. 6-9.

Fig 6-9. Formation of a biofilm. (Harrison et al., 2005)
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Biofilms are involved in many diseases such as endocarditis, lung infections in cystic fibrosis, ear infections, and dental plaque. Medical implants such as artificial heart valves, joint replacements and indwelling catheters can support the growth of biofilms which become the source of infection. Biofilms can contain one to several species of bacteria which can communicate and transfer genes between each other.
Although they don’t look like it under a light microscope, biofilms are actually well organized with channels for water, nutrients and oxygen and persister cells that are metabolically modified to increase their survival under adverse conditions. An example of how a biofilms might be organized is shown in Fig. 6-10.

Fig. 6-10. Example of biofilm structure. (Harrison et al., 2005)
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Bacteria in biofilms resist antibiotics in several ways that are not available to individual cells, including 1) quorum sensing systems of communication, 2) decreased penetration of the antibiotic into the biofilms matrix, 3) increased use of cellular pumps to keep antibiotics out of the cells and 4) genetic switches that turn susceptible cells into antibiotic-resistance persister cells. (Leid, 2009) Antibiotic treatments may kill susceptible cells but persister cells can remain in the biofilms matrix and grow after the antibiotic concentration goes down.
Biofilms also protect bacteria by affecting the response of the immune system against the bacterial cells. Leukocytes and their products as well as phagocytes are limited in their ability to invade the biofilms and act on the bacteria. (Leid, 2009)
Investigation 5: Persistent Middle Ear Infections
1.
Some children respond to antibiotic treatment of a middle ear infection and do not have frequent recurrences while other children have recurring infections every few weeks. Describe the sequence of events that could lead to recurring ear infections.
Resources for investigation:
Biofilm Basics: An introduction http://www.biofilm.montana.edu/biofilm-basics.html

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Slideshow of household biofilms http://www.biofilm.montana.edu/content/household-biofilms
Ear infections and biofilms http://www.technologyreview.com/Biotech/17150/
YouTube video on biofilms http://www.youtube.com/watch?v=XVJ6FQTIDG8
Finding the Source of Antibiotic Resistant Bacteria
What is the source of antibiotic resistant bacteria and why are they becoming more common? Antibiotic resistance initially develops in a cell due to a mutation in the DNA. The new resistant gene can be spread to other organisms by horizontal transfer using the mechanisms of transformation and more often conjugation. Many resistant genes originally came from environmental organisms found in soil, water and food (Marshall et al., 2009). Soil organisms produce a variety of antibiotics which serve as both “weapons” to protect themselves from competition with other species and as chemical signals between cells. Antibiotic resistant genes likely evolved at the same time as the antibiotic genes and helped the cells resist the
“weapons” action of antibiotics from other organisms. Thus, the environmental organisms became a reservoir for antibiotic resistance genes.
Humans and other animals are regularly exposed to bacteria from environmental sources and some of these bacteria can become transient colonizers of our skin, nose, throat and intestinal tract. These organisms develop a commensal relationship with humans and animals, defined as a relationship in which one organism (the bacteria) benefits and the other organism (human) is not harmed. They are referred to as transient because they only temporarily reside on the human.
During their temporary residence on the human, there is the opportunity for horizontal gene transfer of antibiotic resistance genes from the transient commensals to the core colonizers or normal flora of the human (Marshall et al., 2009). The next step in the transfer of antibiotic genes occurs when pathogens and opportunistic pathogens receive the antibiotic resistance genes through conjugation or transformation.
Overuse of Prescription Antibiotics Increases Antibiotic Resistance
The overuse use and the inappropriate use of antibiotics in medicine are thought be the major cause for an increase in antibiotic resistant, pathogenic bacteria.
The more antibiotics that are prescribed, the more selective pressure there is for resistant strains to survive and cause future infections.
A recent study in Europe looked at the rate of antibiotic consumption versus the incidence of antimicrobial resistance for 21 countries. The data came from the
European Surveillance of Antimicrobial Consumption (ESAC) and the European
Antimicrobial Resistance Surveillance System (EARSS). These two organizations compile surveillance data from Europe and make it available on interactive web sites. Figures 6-11 and 6-12 below were based this data base.

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Investigation 6: Relationship between antibiotic use and incidence of antibiotic resistance
1.
Use Figures 6-11 and 6-12 to answer the questions below. The data are based on defined daily dose (DDD) which is defined by the WHO as the average maintenance dose per day per adult. a.
Examine the graphs to determine if there is a correlation between the amount of antibiotic consumption and the percent of antibiotic resistant infections. Write one to two paragraphs answering these questions: Were the countries that used the lowest amount of antibiotics the same as the countries that had the lowest percent resistance? Were the countries that used the highest amount of antibiotics the same as the countries with the highest percent resistance? What were the differences? b.
What types of country-specific differences could affect the data? (e.g. vaccination policy)
Four of the 7 countries that prescribed the lowest amount of antibiotics were also in the lowest group of 7 countries for antibiotic resistance: Denmark, Netherlands, United
Kingdom, and Sweden. Four of the six countries using the most antibiotics were also in the top six countries for antibiotic resistance: Luxemburg, Portugal, Belgium and
France. One difference is that antibiotics were highly prescribed in Greece but Greece has a low resistance rate.
There is a note that the data for Greece is incomplete.
Items that could affect the country wide data include: vaccination policy, regional differences in prescription rates within a country, general availability and access to health care, hygiene, infection control measures and consumer attitudes.

Figure 6-11. Total antimicrobial drug consumption in outpatient care in DDD per
1000 inhabitants per day (DID) by antimicrobial class in 21 European countries in
2006. (van de Sande-Bruinsma, 2008)
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Country designations: AT, Austria; BE, Belgium; BG, Bulgaria; CZ, Czech
Republic; DE, Germany; DK, Denmark; ES, Spain; FI, Finland; FR, France; GR,
Greece; HR, Croatia; HU, Hungary; IE, Ireland; LU, Luxembourg; NL, the
Netherlands; PT, Portugal; SE, Sweden; SI, Slovenia; SK, Slovakia; UK, United
Kingdom.
Figure 6-12. Proportion of penicillin-nonsusceptible Streptococcus pneumonia
(PNSP), erythromycin-nonsusceptible S. pneumonia (ENSP), and fluoroquinoloneresistant Escherichia coli (FQRE) in 2005, ranked in descending order by countries with the highest percent resistance to lowest as indicated by number above the bars.
(van de Sande-Bruinsma, 2008) (* = Incomplete data)

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2.
The first European Antibiotics Awareness Day was held in 2008.
View the video and look at the fact sheet that was designed for the
Day. The Centers for Disease Control in the US has also designed an antibiotic awareness program called “Get Smart about
Antibiotics.” The first event was held in fall 2008, and was repeated in October 2009. Review the materials at the CDC website. a.
Health promotion and health education are important aspects of public health programs. If you were designing an antibiotic awareness day for a large, populous and diverse country like the U.S., what factors would you need to keep in mind? b.
Write an article for your college newspaper or your community newspaper to raise awareness about the conditions that lead to antibiotic resistance. Remember to adapt your message to the audience you are targeting. Use your own words.
Some factors to consider include: language of materials, ways to communicate with different generations, variety of health

19 care delivery options, reaching people who do not use media, targeting primary care physicians, and delivery to school-age children.
Resources for investigation:
European Antibiotics Awareness Day http://ecdc.europa.eu/en/EAAD/Pages/Home.aspx/
CDC Get Smart about Antibiotics http://www.cdc.gov/getsmart/campaign-materials/week.html
Self medication with antibiotics can contribute to an increase in antibiotic resistance in the community. A recent survey in 19 countries of Europe showed that from 1 to 200 people per 1000 inhabitants took antibiotics without seeking a doctor’s opinion. From 80 to 449 people per 1000 inhabitants intended to self medicate if needed. (Grigoryan, 2006) In some cases people were able to obtain the antibiotics from pharmacies without prescriptions, even though this was against the law in the countries covered in this survey. Others had left-over antibiotics at home.
Antibiotics are available from pharmacies without a prescription in many parts of the world even though the country may have laws controlling the how the drugs are dispensed. On every continent there are towns where people can go to the pharmacy and buy antibiotics for their infections on the advice of the pharmacist.
Unfortunately, some of the infections are caused by viruses which don’t respond to bacterial antibiotics and some infections are caused by bacteria resistant to the antibiotic.
3.
Read the article, “Are we killing the cures?” from the Pan
American Health. a. Describe at least two things that can occur when a person buys antibiotics from the pharmacy without a prescription. b. Explain how these actions promote the development of antibiotic resistance?
When people buy antibiotics from a pharmacy without a prescription, they may only buy enough for one or a few days.
They may buy the wrong antibiotic for the infection or one that is no longer effective due to the development of antibiotic resistance.
Buying an insufficient amount of antibiotic leads to the drug killing the most susceptible organisms while leaving the more resistant cells to grow. This applies both to the species that is causing the infection and other bacteria in the body. Using the wrong drug unnecessarily exposes the microbial flora of the body to antibiotics and resistant survive while sensitive strains die.

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Self-medication may lead to a more serious infection if the drug is not effective. The patient may end up with a longer illness and higher exposure to antibiotics.
Resources for investigation:
Are we killing the cures? http://www.tufts.edu/med/apua/Pubs/Articles/PerspectivesInHealthM aga.pdf
Agriculture and Antibiotic Resistance
Antibiotics are added to animal feed for the therapeutic treatment of disease, the prevention of disease, and at low levels for growth promotion. Low levels of certain antibiotics are used for long periods of time to increase the growth rate of livestock while therapeutic treatment uses high levels for short periods of time to treat a specific infection.
The Union of Concerned Scientists estimates that at least 24.6 million pounds of antibiotics are used each year in animal (poultry, swine, and cattle) agriculture.
This compares with 3 million pounds of antibiotics used in human medicine, or oneeighth the amount used in farm animals. Of the 24.6 million pounds, about 70% are used for non-therapeutic purposes such as growth promotion.
The presence of antibiotics in animal feed creates selective pressure by inhibiting the antibiotic-sensitive bacteria and allowing the resistant organisms to grow. Organisms of particular concern are animal pathogens that can cause disease in humans and organisms that can colonize humans as commensal bacteria. When commensals develop antibiotic resistance and colonize humans, they can transfer their resistance genes to human pathogens. Salmonella sp. and Campylobacter are two examples of animal pathogens that can cause zoonoses, animal diseases that occur in humans.
Investigation 7: From Farm to Food to Family
1.
The flow chart in Figure 6-13 shows possible ways that antibioticresistant bacteria can be transferred from the farm to humans and indicates some of the outcomes. a.
Describe how antibiotic-resistant bacteria might be spread to the community by humans in direct contact with the animals. Explain the pathway from the farm to the food production plant to humans. b.
Are more humans likely to pick up bacteria directly from the live animals or from the food chain? Explain. Why is there an arrow from humans to hospital-acquired infections?

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The flow of antibiotic resistance bacteria (ARB) from the farm to the community by direct human contact involves farm workers acquiring ARB from handling the animals.
From the workers ARB can be transferred to family; and from family to others in the community through school, sports and other contact. The ARB may not be human pathogens but the resistance genes can be transferred from the commensal organisms to pathogens in the human body.
The path through food production begins with ARB getting on meat during slaughter and being carried to meat markets and purchased by consumers who pick up the
ARB in the kitchen or in undercooked foods. Fruits and vegetables can pick up ARB from contaminated soil and water. These foods may go to the market fresh and carry organisms into people’s kitchens or may be partially processed, e.g. shredded lettuce, and then purchased.
There are more opportunities for ARB to move into the community through the food production route.
People who are colonized with antibiotic-resistant organisms may enter the hospital for reasons other than infection. During the hospitalization the antibioticresistant organisms may cause an infection secondary to the patient’s main diagnosis. This infection can be spread to other patients and staff if infection control measures fail.

Figure 6-13. Flow chart for the potential movement of antibiotic resistant bacteria from the agricultural setting to community and healthcare settings. (Adapted from
Sørum, Smith, and Martínez)
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Key: HA = hospital-acquired, CA = community-acquired, Carrier = human colonized with resistant-bacteria but not ill, Infection cleared = human recovered from infection and did not become a carrier
The non-therapeutic use of antibiotics as growth promoters has been actively debated for years around the world. There is substanial evidence that non-therapeutic use of antibiotics does exert selective pressure for resistant bacteria. For example, in Denmark chicken and pig producers volutarily stopped using antibiotic growth promoters and saw a significant reduction in the percent of antibiotic resistant bacteria in their animals. (Aarestrup, 2001)
Food producers had warned that more pathogens could enter the food chain if non-therapeutic antibiotics were banned.
The European Union banned the use of antibiotics as growth promoters in animal feeds in January 2006 based on the “precautionary principle.” The precautionary principle states that if the body of evidence supports that a process is harmful, even if there is not complete scientific concensus, then action should be taken to protect the public. As more evidence becomes available in the future, the action can be modified.
In the U.S., legislation has been introduced several times to preserve antibiotics for human medical treatment by cutting back on non-therapeutic use in animal feeds. The legislation is supported by consumer, environmental and medical groups but opposed by agricultural groups. Agricultural groups make the point that researchers have not determined the relative contributions of the two main causes for the rise of antibiotic resistance: 1) Over prescription of antibiotics in human medicine; 2) Use of non-therapeutic

23 levels of antibiotics in animal feeds. They maintain that relative to the benefits of reducing food poisoning incidents, non-therapeutic levels of antibiotics in feeds make a small contribution to antibiotic resistant infections in humans. Quantitating the contributions of over-prescribing antibiotics for humans versus using antibiotics in animal feeds is difficult because of the complexity of the pathways.
2.
Assume that a bill, “Preservation of Antibiotics for Medical
Treatment Act”, calling for the ban of non-therapeutic antibiotics in animal feeds has been introduced in Congress. Pick either the support or opposition side and write 2-3 paragraphs giving scientifically based arguments to support your stand.
Supporters side: Using non-therapeutic levels of antibiotics creates selective presure that allows the resistant organisms to survive. Even if the antibiotics used in feeds are not the exact ones used in humans, organisms can develop resistance to the
“class” of antibiotics and thus resistant to the human formulation.
Experience in the EU banned. A great deal of data supports the conclusion that the low levels of antibiotics cause an increase in
ARB in livestock. The precautionary principle is easily applied to this case.
Opponents side: There is no way to quantitate the relative importance of over-prescribing human antibiotics and using nontherapeutic levels of antibiotics in feeds. Antibiotics in feeds may be making an insignificant difference in the number of ARB. If you cut out non-therapeutic antibiotics, you may see an increase in animal pathogens in animals that can be transferred to humans in the food chain. Banning antibiotics will mean more sick animals on the farm which will require more therapeutic use of antibiotics and also increase the cost of food for consumers.
Resources for investigation:
Pew Commission on Industrial Farm Animal Production http://www.ncifap.org/
Union of Concerned Scientists http://www.ucsusa.org/food_and_agriculture/science_and_impact s/impacts_industrial_agriculture/hogging-it-estimates-of.html
EU Ban on Antibiotics http://europa.eu/rapid/pressReleasesAction.do?reference=IP/05/16
87&format=HTML&aged=0&language=EN&guiLanguage=en

24
Farm Bureau http://www.fb.org/index.php?fuseaction=newsroom.newsfocus&y ear=2007&file=nr0329.html
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