Health Letter, January 2014
On Sept. 16, 2013, the Centers for Disease Control and Prevention (CDC) issued a sobering report about the growing worldwide public health threat posed by the spread of antibiotic-resistant bacteria. At least 2 million Americans each year develop serious infections with antibiotic-resistant bacteria, and at least 23,000 patients die as a direct result of such infections, according to the CDC report, entitled “Antibiotic Resistance Threats in the United States, 2013.” Many other patients die from other medical conditions that were complicated by such infections.
In a foreword to the report, CDC director Tom Frieden succinctly summarized the problem:
Antimicrobial resistance is one of our most serious health threats. Infections from resistant bacteria are now too common, and some pathogens have even become resistant to multiple types or classes of antibiotics (antimicrobials used to treat bacterial infections).The loss of effective antibiotics will undermine our ability to fight infectious diseases and manage the infectious complications common in vulnerable patients undergoing chemotherapy for cancer, dialysis for renal failure, and surgery, especially organ transplantation, for which the ability to treat secondary infections is crucial.
The discovery of penicillin, the first antibiotic used clinically 70 years ago, and the subsequent development of multiple classes of antibiotics represent one of the most remarkable advances in modern medicine. Not only have these drugs directly saved millions of lives, they also made possible many other life-saving advances in medicine, some of which are alluded to in Dr. Frieden’s comments above. Left unchecked, the growing problem of antibiotic-resistant bacteria has the potential to return clinical medicine to the pre-antibiotic era, which would have catastrophic public health consequences.
Factors contributing to antibiotic resistance
The phenomenon of drug resistance has been well-recognized since the introduction of penicillin into clinical medicine. Ironically, the very use of antibiotics to treat infectious diseases leads inexorably to the development of antibiotic-resistant germs. The more antibiotics are used, the faster bacteria develop antibiotic resistance to them.
The diagram below, reprinted from the CDC report “Antibiotic Resistance Threats in the United States, 2013,” provides a useful basic overview of how bacteria develop antibiotic resistance and how antibiotic resistance can spread through the community. It can also be viewed on page 14 of the full report, available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.
Antibiotic resistance occurs because bacteria are constantly evolving due to mutations in their genes. The top panel of the figure (“How Antibiotic Resistance Happens”) shows that when a population of bacteria is exposed to an antibiotic, most of the bacteria initially will be sensitive to it and be killed. However, a very small fraction of the bacteria will have a genetic mutation that makes them resistant to the antibiotic, allowing them to survive. These surviving bacteria will multiply, creating a larger population of antibiotic-resistant organisms. Particularly troubling, bacteria have the ability to transfer copies of genes that provide antibiotic resistance to other bacteria nearby – even to different species of bacteria. Over time, a population of bacteria can acquire resistance to multiple different types of antibiotics.
The lower panel in the figure (“Examples of How Antibiotic Resistance Spreads”) demonstrates the various pathways by which antibiotic-resistant germs spread through the general community. As an initial step, antibiotic resistance can develop in the usually beneficial bacteria normally present in the guts of both humans and animals upon exposure to any antibiotic. Such bacteria from animals can spread to people through consumption of both meats and vegetables that become contaminated with those bacteria. In addition, antibiotic-resistant bacteria can spread from person to person in the health care setting, such as a hospital, and in the general community. Under the right circumstances, these bacteria can subsequently lead to infections in some people and can be difficult to treat due to the antibiotic resistance.
In the most extreme cases, a population of bacteria can acquire resistance to all available types of antibiotics. Infections with these so-called “superbugs” are particularly dangerous, and in some cases they are only treatable with experimental drugs.
Inappropriate use of antibiotics fuels problem
Unnecessary and inappropriate use of antibiotics in both people and food-producing animals has long been recognized as the most important factor contributing to the spread of antibiotic-resistant bacteria.
The CDC estimated that as many as half of all antibiotics prescribed to human patients are “not needed or are not optimally effective as prescribed.” The medical profession has known for years that antibiotics are too often prescribed inappropriately for viral infections, such as those resulting in colds, sore throats and bronchitis. Antibiotics have no effect on viral infections and therefore offer no benefit. Furthermore, their use will promote the development of resistant bacteria in the patient’s gut. Frequently in circumstances in which a bacterial infection is causing a patient’s illness, broad-spectrum antibiotics that can kill many different types of bacteria are prescribed when a narrow-spectrum antibiotic that only kills one or a few types of bacteria would suffice.
Medical societies and government agencies such as the CDC have attempted for years to curb the inappropriate use of antibiotics. However, a recent study published online by JAMA Internal Medicine on Oct. 3, 2013, reveals that these efforts have been inadequate. The authors of the study looked at trends in antibiotic prescribing rates for treatment of adult American patients with sore throats. Most sore throats in adults and children are due to a virus. Only about 10 percent are caused by strep bacteria (formally known as Group A Streptococcus) and thus require antibiotic therapy. Nevertheless, between 2000 and 2010, the rate at which physicians prescribed antibiotics to adult patients across the U.S. visiting their doctors with sore throats has held steady at approximately 60 percent, a rate that far exceeds the 10 percent prevalence rate of sore throats due to bacterial strep infections. Also troubling was the observation that during 2009 to 2010, azithromycin – an expensive, powerful antibiotic not needed for the treatment of strep throat – was prescribed for 15 percent of medical visits for sore throat.
Widespread inappropriate use of antibiotics in food-producing animals also has played an important role in the development of antibiotic-resistant bacteria. More than 80 percent of all antibiotics used in the U.S. are administered to food-producing animals, and the majority of this use is unrelated to treatment of infections. Rather, most such animal use is to promote animal growth to increase food production.
Addressing the antibiotic-resistance threat
In its report, the CDC identified four critical actions that must be taken to prevent and counter bacterial antibiotic resistance.
The first step is to prevent bacterial infections. Preventing infections reduces the need to use antibiotics for treatment. Less antibiotic use lowers the rate of development of antibiotic resistance. Preventing infections also will limit the spread of antibiotic-resistant bacteria to other people. Some of the measures that can be used to prevent such bacterial infections include enhanced tracking of antibiotic-resistant infections by health care facilities and providers, use of vaccines such as the pneumococcal vaccine, appropriate isolation procedures for infected patients, and safe food handling and preparation practices.
The second step is for the CDC and other public health agencies to collect data on antibiotic-resistant infections and the causes of such infections. This data will provide a basis for developing specific strategies to prevent the spread of these infections.
The third and perhaps most important step to address the antibiotic-resistance threat is to improve the prescribing and use of antibiotics in both people and food-producing animals. Antibiotics should be used in people for bacterial infections only, and never for viral infections. Moreover, when antibiotic treatment is needed, the most appropriate antibiotic that targets the type of bacteria causing the infection should be prescribed. Nontherapeutic use of antibiotics in food-producing animals for the purpose of promoting animal growth must be eliminated. This is particularly critical for those antibiotic classes that are used to treat infections in people. To this end, the Food and Drug Administration (FDA) on Dec. 11, 2013, announced a “voluntary plan with industry to phase out the use of certain antibiotics for enhanced food production.” Unfortunately, the plan, to be implemented over a three-year period, is likely to have limited impact because it still will allow large-scale use of antibiotics in food-producing animals to control or prevent disease.
The fourth step is to develop new antibiotics. New antibiotics will always need to be developed because resistance will inevitably develop, even when all uses of antibiotics are appropriate due to the natural evolution of bacteria. The CDC noted that there has been a steady decrease in the number of new antibiotics developed and approved by the FDA over the past 30 years. Because of the economic considerations, many drug companies have chosen not to invest in the development of new antibiotics. Although the need for increased development of new antibiotics is obvious, it is imperative that the standards for ensuring the safety and effectiveness of these drugs not be lowered. One solution not mentioned by the CDC is the need for more public funding from the National Institutes of Health and other federal agencies for the development of new antibiotics.
The problem of antibiotic-resistant bacterial infections will almost certainly get worse before it gets better. Health care providers and patients must realize that antibiotics are a precious, and ultimately time-limited, resource and must be used judiciously. Patients should not pressure their health care providers to prescribe antibiotics for symptoms that are likely due to viral illnesses, and health care providers must resist any such pressure and counsel patients on the dangers of inappropriate antibiotic use. With these and the other actions outlined by the CDC, the threat posed by antibiotic-resistant bacteria can be overcome.