Every year, the United States produces 51 million pounds of antibiotics, but only half is medicine for humans.¹ The other half is used to protect livestock and fruit trees.¹ Other nations similarly use another 200 million to 400 million pounds of antibiotics.² This extraordinary practice has created an alarming acceleration of antibiotic-resistant bacteria, “super bugs” that prey on our patients.

Pathogenic bacteria, many of them infectious to higher organisms, have existed for a long time, perhaps as long as there have been hosts that allow their propagation. We know that dinosaurs living 150 million years ago suffered from bacterial infections. In more recent history, we know that bacterial pathogens are responsible for untold misery and countless deaths for most forms of life and, most notably, for human beings. Much of human history has been shaped by disease, and most of that caused by pathogenic bacteria.

Before the relatively recent advent of antibiotics, bacterial infections were a constant terror. Even minor cuts and scrapes often became infected and resulted in the loss of life or limb. Imagine, then, the relief when a better understanding of bacterial infection led to the first antibiotics — a remedy that effectively killed the invaders and promised to save the human race from one of its oldest and worst enemies. Penicillin and the sulfa drugs were thought to be miracles when they first came out in the 1930s and 1940s. Their effectiveness was spectacular, and there was no reason to think it would ever be otherwise. However, the euphoria wasn’t to last long: The targeted organisms had an ability to develop a progressive resistance to these early antibiotics — and within a relatively short time. The first to start losing effectiveness was penicillin, and in less than a decade, penicillin was rendered ineffective against a common bacteria, Staphylococcus aureus.^3,4 Despite the development of more than 100 antibiotics since penicillin, bacteria have been able to develop resistance to each, usually in a few months or years.

Bacterial resistance can occur whenever an antibiotic is used. Sensitive strains of the bacteria are killed by the drug while resistant strains survive and continue to multiply — a process known as selective pressure. Unfortunately, because antibiotics are excreted after use relatively unchanged into the environment, they can continue to exert selective pressure on other bacteria.^2,5 During the last 50 years, an estimated 1 million metric tons (2,200,000,000 pounds) of antibiotics have been released into the environment.⁶ As a result, antibiotics and resistant bacteria can be detected in municipal waters, streams, rivers, and fields.

Antibiotics and agriculture

Using subtherapeutic doses of antibiotics for food animals leads to the development of resistant bacteria that can spread to humans through the food chain. Cattle, poultry, and pigs are routinely given antibiotics for prophylaxis and to promote growth, a practice that has jeopardized the effectiveness of many of the antibiotics used for treating human diseases. For example, avoparcin, an antibiotic used in Europe to enhance animal growth, has led to the emergence of vancomycin-resistant enterococci (VRE) among animals.⁷ This same strain of virtually untreatable VRE has been passed on to humans.

Another antibiotic growth promoter fed to cattle and chicken in the United States, virginiamycin (similar to vancomycin), has led to the emergence of enterococci that are resistant to both vancomycin and quinupristin/dalfopristin (Synercid), a new drug recently approved to treat human patients with life-threatening infections caused by VRE.⁷ A third example is the use of fluoroquinolones in poultry. Chickens are treated with fluoroquinolones to prevent mortality from Escherichia coli and Campylobacter jejuni. This treatment has led to the emergence of fluoroquinolone-resistant strains of campylobacter in chickens that can be passed on to humans in the food chain.⁸ Each year, 2.4 million Americans become infected with campylobacter from preparing and eating contaminated food animals, particularly chickens. Campylobacter food-related infections are the most common bacterial cause of human diarrhea in the United States and one out of six infections is resistant to fluoroquinolones.⁸ It is interesting to note that 88% of commercially available chickens are culture positive for campylobacter.⁸ Today, invasive human infections caused by campylobacter and salmonella, as well as urinary tract infections and respiratory tract infections, are treated with fluoroquinolones, such as levofloxacin (Levaquin) and ciprofloxacin (Cipro); however, their continued use is jeopardized by increasing resistance.⁸

Antibiotics and human medicine

Not all antibiotic resistance can be ascribed to the use of antibiotics in animal husbandry and agriculture. The inappropriate use of antibiotics for treating human illnesses is probably the more important contributor to the increase in antibiotic resistance.^1,8 Today, antibiotics are the second-most commonly prescribed class of drugs in the United States, and, according to the Centers for Disease Control and Prevention, nearly half of these antibiotics should not be prescribed.⁹ For example, 25% to 45% of the 190 million doses of antibiotics given each day in hospitals are considered inappropriate, and in the outpatient setting, up to half of 145 million courses of prescribed antibiotics are not medically justified.⁹

Most antibiotic resistance emerges in hospitals, where antibiotics are given to nearly all intensive care patients and almost half of all other patients, and as the numbers of prescriptions have gone up, so has the incidence of resistance.⁹ In just five years (1994-1999), resistance among four of the most common pathogens, associated with hospital and community-acquired infections, increased between 40% and 49%. (The pathogens are S. aureus, Enterococci, E. coli, and Pseudomonas aeruginosa.)¹⁰ During this same period, strains of three life-threatening bacteria, vancomycin-resistant Enterococcus faecium, Mycobacterium tuberculosis, and Pseudomonas aeruginosa, became resistant to all of the more than 100 antibiotics available for systemic use in human illnesses.⁹ Today in U.S. hospitals, multidrug resistance has become the norm for pneumococci, enterococci, and staphylococci,³ and more than 70% of hospital-acquired infections are resistant to one or more of the drugs commonly used for treatment.^11,12

The majority of antibiotics prescribed for adults in outpatient settings are for upper respiratory tract infections, such as sinusitis, bronchitis, and the common cold. These illnesses, which are nearly always caused by viruses for which antibiotics offer no benefits, are the most frequent reasons for outpatient visits and account for up to 75% of total antibiotic prescriptions each year.¹³ In several studies examining the justification for prescribing antibiotics for viral infections, physicians explain that unrealistic patient expectations and demands for antibiotics are the major reason for prescribing the drugs.^9,13 Patients often are not satisfied with a visit to their physician unless they leave with an antibiotic prescription, regardless of whether it is indicated for their condition.

Many patients with upper respiratory infections believe antibiotics will hasten their recovery. In a Los Angeles County Health survey (2002-03) of more than 8,000 adults, 46% of respondents reported that they call their physician for antibiotics when they have a cold or the flu.¹⁴ In another national telephone survey on consumers’ knowledge and use of antibiotics conducted by the Foodborne Diseases Active Surveillance Network, more than 10,000 adults were interviewed. About 27% of respondents believed that antibiotics would cure a cold more quickly, 32% believed that taking antibiotics when they had a cold would prevent more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention.¹⁴

In response to the widespread, indiscriminant prescribing of antibiotics for respiratory illnesses, the CDC developed practice guidelines for appropriate antibiotic use and started a campaign aimed at health providers and patients.¹⁵ In October 2006, the CDC released a new guidelines (Management of Multidrug-Resistant Organisms In Healthcare Settings) for preventing the spread of antibiotic-resistant infections in hospitals. ¹⁶

Antibacterial agents

Antibacterial agents are an additional cause of bacterial resistance. Antibacterials can be found in every home, and, like antibiotics, they kill off susceptible bacteria, leaving only the resistant “super bugs” alive. These agents have been added to more than 700 household products including mattresses, pillows, sheets, slippers, towels, kitchen tools, cutting boards, toys, soaps, toothpaste, and cleansers. Antibacterials come in two forms, short-acting forms used as surface cleansers (alcohol, chlorine) and longer-lasting forms (triclosan, benzalkonium chloride) bonded/impregnated into the household products. The short-acting agents, because of their rapid killing effect, are not thought to cause bacterial resistance.¹ However, studies suggest that longer-lasting antibacterial agents, such as triclosan, are capable of selecting for resistant bacteria.¹ A few laboratory-based studies have suggested a possible link between the emergence of community-acquired methicillin-resistance S. aureus (cMRSA) and the use of antibacterial products.¹

Bacterial mechanisms of resistance

Bacteria can become resistant to antibiotics in a number of ways. They can become resistant to certain drugs by spontaneous genetic mutations (errors that occur naturally in the process of replication), or they can receive new genetic material conveying resistant genes (plasmids, small circular pieces of DNA) from other resistant bacteria.¹

Whenever a bacterium is able to develop resistance to an antibiotic, it can replicate itself every 20 minutes, becoming 1 million bacteria in seven hours, 1 billion bacteria in 10 hours, and a number followed by 21 zeros in 24 hours.

S. aureus

S. aureus, the leading cause of hospital-acquired infections in the United States, will be used here to illustrate the development of bacterial resistance.⁹ Staphylococci can be found everywhere and are able to survive for long periods of time under adverse environmental conditions by expelling water and going into a dormant state. Humans are a natural reservoir for S. aureus, and as many as 30% to 50% of adults are colonized with the bacteria without any signs of inflammation or infection.^15,17 The higher colonization rates are found in health care workers, hospitalized patients, dialysis patients, insulin-dependent diabetics, injection drug users, and people with eczematous skin diseases. The bacteria most commonly colonizes the anterior nares although other sites, such as the axillae, vagina, pharynx, and damaged skin surfaces also can be colonized.^15,17 At least half of people with nasal colonization carry S. aureus on their hands. These asymptomatic carriers are a frequent source of the bacteria since shedding from the skin or nasopharynx is common. Clinically, S. aureus is a major cause of skin, soft tissue, bone, joint, respiratory, and endovascular disorders as well as toxin-mediated food poisoning and toxic shock syndrome.^15,17 In U.S. hospitals, S. aureus is the primary cause of bloodstream infections, pneumonias, skin and soft tissue infections, and in ICUs S. aureus is the most common cause of all types of infections.³

Before antibiotics were made available in the early 1940s, invasive S. aureus infections were fatal more than 80% of the time.¹⁵ With penicillin, mortality for invasive disease was reduced by more than half and now ranges from 11% to 43%.¹⁵ However, within six years after the initial use of penicillin, 25% of hospital strains of S. aureus were able to inactivate the drug by producing a plasmid-mediated enzyme called penicillinase (also called beta-lactamase).³ Resistance then increased rapidly, and by the late 1960s, more than 80% of S. aureus isolates were resistant to penicillin.^3,17 Today, resistance to penicillin is more than 90%.^3,9

Methicillin (Staphcillin), a semi-synthetic penicillin derivative relatively resistant to beta-lactamase, was introduced in 1960, and at that time, all S. aureus including penicillin-resistant strains, were susceptible to the new drug.^11,17 Unfortunately, within one year, the first methicillin-resistant strains of S. aureus (MRSA) appeared, in Europe. The resistant bacteria were able to keep the methicillin from binding to the target site on the bacterial cell wall by altering the target of the antibiotic. Resistance to methicillin results in similar resistance to all beta-lactam antibiotics, including all penicillins, cephalosporins (e.g., Ancef, Kefzol), and carbapenems (e.g., Imipenem). Furthermore, methicillin-resistant S. aureus (MRSA) often demonstrate multidrug resistance to many other kinds of antibiotics such as erythromycin, clindamycin (Cleosin), gentamycin (Garamycin), trimethoprim-sulfamethoxazole (Bactrim), ciprofloxacin (Cipro), and tetracyclines. Methicillin resistance developed more slowly than did penicillin resistance, and it was nearly 30 years before widespread resistance occurred. Between 1975 and 1991, the percentage of S. aureus resistant to methicillin increased from 2.4% to 29.14% During the next decade, the rates of resistance accelerated, and by 2000, more than 55% of hospital-acquired S. aureus isolates were resistant to methicillin, and as many as 80,000 hospitalized patients were becoming infected with the resistant organism each year.¹⁸

Since 2000, the problem has become more serious in U.S. hospitals. In 2004 (the latest data), more than 60% of S. aureus isolates were methicillin resistant.⁴

In addition, new “community-acquired” strains of methicillin-resistant S. aureus have emerged. Community-acquired MRSA usually presents as skin and soft tissue infections. However, life-threatening invasive infections such as necrotizing pneumonia, necrotizing fasciitis, or rapidly fatal septicemia can also occur.^4,17 Approximately 30% of the S. aureus infections acquired in the community (CA-MRSA) are methicillin-resistant.¹²

As resistance to the semi-synthetic penicillins (methicillin) increased, vancomycin, the only remaining antibiotic consistently effective against all strains of S. aureus, became the drug of choice for treatment of serious infections. Vancomycin has been available for more than 30 years, and until recently, there have been no strains of S. aureus that would not respond to the drug. Nevertheless, when the first cases of vancomycin-resistant enterococci were reported in the United States, in 1988, it was fully recognized that S. aureus also might become resistant to vancomycin.⁵ As expected, 14 years later, in 2002, the CDC reported on the first health care-associated infection with S. aureus completely resistant to vancomycin (VRSA).¹⁹ S. aureus had acquired a gene for resistance through a transfer of genetic material from a vancomycin-resistant enterococcus into a MRSA strain.¹⁹ Recently, an epidemic strain of CA-MRSA has developed intermediate resistance to vancomycin.²⁰

Fortunately, four new antibiotics, quinupristin-dalfopristin (Synercid), linezolid (Zyvox), daptomycin (Cubicin), and tigecycline (Tygacil), have become available for treating patients with infections resistant to vancomycin. However, shortly after their clinical introduction, resistance to quinupristin-dalfopristin and linezolid was reported. With resistance increasing, it is not known how long these new drugs will remain effective in treating VRE and VRSA.^3,4

Clearly, the continued development of new antibiotics is not the answer to resistance. The spread of resistance needs to be controlled. Several northern European countries have had some success in controlling the spread of resistant strains of bacteria. While the numbers of S. aureus isolates resistant to methicillin have continued to climb to more than 55% in U.S. hospitals, resistance to S. aureus has been controlled in Denmark, Finland, and the Netherlands.¹¹ For example, in Denmark in the 1960s, one-third of S. aureus blood isolates were resistant to methicillin. Today, less than 1% are resistant.¹¹ Similarly, in Finland and the Netherlands, MRSA prevalence has been maintained at less than 0.5%.¹¹ These countries have controlled MRSA resistance with rigorous national infection control policies that emphasize strict barrier precautions for patients colonized or infected with MRSA. In addition, surveillance cultures are taken of each patient entering the hospital to identify colonized patients.¹¹

The nurse’s role

The increasing numbers of MRSA infections in U.S. hospitals are essentially an infection control problem caused by poor compliance with handwashing; lack of barrier precautions, such as gowns and gloves; and insufficient cleaning of a contaminated hospital environment. Patients infected or colonized with MRSA acquire their infections from an external source, most often the hands of a healthcare worker.¹¹ Nurses have a vital role in managing antibiotic resistance by ensuring that everyone who has contact with their patients adheres to appropriate infection control practices. They can also educate patients on the proper use of antibiotics.