In November 2018, the Organisation for Economic Co-operation and Development (OECD) released a report that predicted antibiotic resistant bacteria (ABR) will cost the U.S. healthcare system $65 billion, outstripping the costs of the flu, HIV, and tuberculosis. The OECD also estimated ABR will claim the lives of more than 2 million victims in North America, Australia, and Europe by 2050. From OECD’s report to alarming articles proposing antibiotic resistant bacteria could become the next existential threat to medical professionals warning of the rising health risks posed by antibiotic resistance, there is an emerging consensus antibiotic resistant bacteria, or superbugs, are becoming a potentially catastrophic threat.
Despite the dangers of superbugs, the Centers for Disease Control and Prevention (CDC) has failed to proactively address the reason behind the problem of antibiotic resistance adequately. Although the introduction of antibiotics has helped curb deaths from treatable bacterial infections, the prevalence of antibiotic misuse, whether via excess usage by patients or via doctors providing unneeded prescription, has accelerated the mutation among the surviving bacteria. Inappropriate antibiotic use has been a long-forming problem; a 2016 collaborative study by the CDC and The Pew Charitable Trusts found at least 30% of antibiotics prescribed in outpatient settings in the United States were unnecessary. Although technological innovation is necessary to combat the current strains of antibiotic resistant bacteria, sans measures to limit the avoidable use of antibiotics, new threatening strains will inevitably arise. As a result, an analysis of why doctors, despite recognizing the perils of antibiotic misuse, continue to over-prescribe them is necessary to reduce inappropriate antibiotic use.
History of Antibiotics and Antibiotics Resistance
Modern research into antibiotics began with the work of a German biochemist named Paul Ehrlich, whose experiments with tissue staining led him to hypothesize scientists could create substances to target specific bacteria in isolation without harming other cells. Paul Ehrlich confirmed his hypothesis when he successfully harnessed the therapeutic properties of methylene blue, a dye used to treat methemoglobinemia (a condition that lowers oxygen levels in tissues), to kill malaria parasites, setting the ground for future antibiotics research.
The next major breakthrough in antibiotics research came with the discovery of antibacterial properties of penicillin by Alexander Fleming, who discovered a type of fungus called Penicillium notatum could more effectively inhibit the growth of Staphylococcus bacteria than the widely available and more toxic disinfectants. However, due to his struggles with extracting and purifying the bacteria-inhibiting ingredients of the fungus in large quantities, it was not until World War II, when Howard Florey and Ernst Chain discovered how to mass produce penicillin, antibiotics became commercially available. Unlike Fleming, who was more interested in how penicillin could be prescribed as a topical antiseptic to treat surface infections, Florey and Chain thought penicillin had potential to inhibit more lethal bacterial diseases. After confirming Fleming’s findings with experiments on mice, Florey and Chain tested penicillin on their first human patient in September, 1940. However, Florey and Chain’s inability to mass produce the antibiotic meant they could not eradicate the infection, and the patient died. Despite their struggles, Florey and Chain continued to experiment with ways to more efficiently produce penicillin and hit a major breakthrough when, with the help of their lab assistant, the two discovered the fungus Penicillium chrysogeum produced 200 times the amount of penicillin as Penicillium notatum. With the discovery of a more effective method to extract penicillin, the drug became widely utilized during World War II, and the death rate from bacterial pneumonia fell from 18% in World War I to 1%, demonstrating the potential of penicillin as a therapeutic agent.
Although penicillin proved effective in treating bacterial infections once considered fatal, the overuse of penicillin, which could even be bought at grocery stores without a prescription or instructions for proper dosage, expedited the mutation of bacteria penicillin was treating. For example, staph aureus is an omnipresent, round-shaped bacterium that can cause many diseases such as pneumonia and acute endocarditis by evading the host’s immune system. In the 1940s, with the introduction of antibiotic penicillin, treatments for staph aureus infections became a routine, uncomplicated process. However, the overuse of penicillin expedited the natural evolution of staph aureus, and, in the 1950s, penicillin-resistant strains of staph aureus began infecting patients. Methicillin, a form of penicillin, was soon introduced as a counter to the penicillin-resistant strains, but, due to irresponsible use of methicillin, in 1961, British scientists discovered the first strains of staph aureus bacteria resistant to methicillin, or Methicillin-resistant Staph aureus (MRSA).
Infections caused by antibiotic-resistant strains of staph aureus, specifically MRSA, has begun ushering in a global health crisis. While MRSA’s ability to spread through seemingly innocuous surfaces such as doctors’ ties or hospital bed curtains has led to infections in unsuspecting patients in hospitals, reports of MRSA infections among people who have not been hospitalized within the past year have appeared in the United States, Asia, South America, Australia, and across Europe among countries with historically low prevalence of MRSA. The global spread of MRSA exemplifies not only the threat posed by antibiotic resistant bacteria but also how antibiotic resistance is developed. Overuse of antibiotics constantly accelerates the evolution of easily treatable strains of bacteria, making them more lethal and more complicated to treat. Interestingly, Fleming, in his Nobel Prize speech for his contributions to the development of antibiotics, foreshadowed the problems we are facing now, noting “the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.”
The Limits of CDC’s Current Policies and Potential Solutions
Recognizing the emerging threat posed by antibiotic resistant bacteria, the CDC has devised the AR Solutions Initiative. With the unprecedented $168 million in funding Congress has appropriated to the CDC, the CDC has launched a variety of activities not only to improve regional response capabilities in the event of an ABR bacteria breakout but also to spur pharmaceutical and diagnostic innovation. Through CDC’s AR Lab Network, the CDC provides regional and state laboratories lacking the capabilities to properly combat an ABR bacteria outbreak with data, technology, and comprehensive lab infrastructure that will allow laboratories to quickly detect signs of an outbreak and initiate the appropriate response protocol. The CDC also promotes more responsible use of antibiotics with guidelines and recommendations for proper antibiotic use both in outpatient and inpatient settings posted on the Center’s website. To spur innovation in pharmaceutical antibiotics research, the CDC and FDA AR Isolate Bank gives the private sector information on a comprehensive set of isolates, or pure samples of agerm, while approved institutions can also request the samples of isolates for research.
Although CDC’s emphasis on containment and innovation are necessary, those policies are also inherently reactionary, requiring the CDC to play catch up to prevent the spread of deadly ABR germs that are constantly mutating. In order to ensure antibiotic resistance does not become an existential threat, addressing the reasons behind excess use of antibiotics propelling bacteria to expeditiously mutate is necessary. For instance, one reason why doctors overprescribe antibiotics is because of liability pressure. In the United States, one in 14 doctors annually face a lawsuit, and studies found doctors often resort to defensive medicine in order to mitigate the risk of a malpractice claim. Analysis of discrepancies in antibiotics prescription between states with different laws for malpractice claims confirms doctors more vulnerable to lawsuits prescribe more antibiotics as security against potential yet unlikely bacterial infections. In states with a cap on noneconomic damages, which alleviates some of the physicians’ liability pressure, doctors were 6 percent less likely to overprescribe antibiotics, which, if extrapolated for all states, could total 3.2 million fewer cases of antibiotics overprescription.
Fear of potential lawsuits is not the only reason why doctors tend to overprescribe antibiotics. A doctor’s decision to prescribe antibiotics is complex, based on a multitude of factors such as the risk of complications and the psychological history of the patient. However, studies show there are ways the CDC can help uncomplicate the physicians’ decisions. A cross-national trial in six European countries demonstrated training the physicians in the use of C-reactive protein (CRP), a protein that can identify pneumonia in hospitalized patients, and engaging doctors in communication training reduced the amount of antibiotics prescriptions for respiratory-tract infections by 62%. That the study achieved reductions across cultural boundaries demonstrate proactive internet-based training can be useful in minimizing the amount of unnecessary antibiotics doctors currently prescribe in all states.
Although technological innovation and improved detection capabilities are important in dealing with the antibiotic resistant bacteria currently affecting patients, if overuse of antibiotics continually drive bacteria to mutate and evolve, there will always be a need for newer solutions. More proactive, prohibitive solutions need to be introduced to complement the policies the CDC is currently pursuing to prevent new strands of superbugs from surfacing. Policies that provide better protection for doctors who are currently incentivized to prescribe unnecessary antibiotics, research into proteins such as CRP with diagnostic value for different infections, and more effective communication training, which will allow doctors to demonstrate to patients why antibiotics prescriptions are unnecessary, could be useful in reducing the amount of antibiotics being prescribed, allowing us to slow down the rate of bacterial mutation.