A 21St Century Medical Dilemma: The Threatening Issue Of Antibiotic Resistance
Before the 20th century, the absence of antibiotics made treating a common ailment like the cold a challenging task. Many people in the United States and abroad succumbed to bacterial and viral infections and did not receive adequate medical attention simply because doctors did not have the proper means to treat these patients (Kessler 2015). All this changed drastically in the 1920’s with Alexander Fleming’s discovery of penicillin (Kessler 2015). Penicillin was deemed a “miraculous drug” (Kessler 2015) and when the mechanisms for penicillin were understood, more antibiotics were produced and what was known as the “golden age of medicine” followed (Kessler 2015). However, even though antibiotics have significantly reduced the incidences of death related to bacterial infections, the potency of antibiotic medication would soon be undermined by many factors. Subsequent to the fortuitous discovery of penicillin, many imagined better health outcomes for patients whose diagnoses were related to infectious bacteria (Kessler 2015).
Now, the 21st century is encountering a potentially uncertain and dangerous reality with the effectiveness of antibiotics seemingly being diminished (Kessler 2015). Anti-microbial resistance is a threat to modern day medicine due to the constant evolutionary changes in microbial DNA, overuse of antibiotics by healthcare professionals and the pharmaceutical complications of introducing new antibiotics.
The emergence of the 20th century was a time of medical innovation and the beginning of what was to later be known as the “golden age of medicine”, and progressions in medical research were made possible after the discovery of antibiotics (Kessler 2015). Although the “golden age” was not so long ago, the transition from a time of predictability and stability was soon followed by a period of uncertainty. The international community became overly confident that the plethora of possible infectious health diseases could be cured by giving patients antibiotics (Kessler 2015). It is also fairly interesting to note that the introduction of modern long-term disorders like diabetes and obesity have become especially common with the overuse of antibiotics (Kessler 2015). The overuse of antibiotics has detrimental and long-term effects on the functioning and integrity of our bodies (Kessler 2015).
Dr. Martin Blaser of the Human Microbiome Program at NYU and the author of “Missing Microbes” explains that the carelessness of healthcare professionals over recent years has contributed to the shift in the microbiome of our bodies (Kessler 2015). So what does Dr. Blaser mean by “microbiome” exactly? The average individual harbors a multitude of beneficial strains of bacteria that is essential to metabolic function as well as protection of the internal organs (Kessler 2015). Dr. Blaser is concerned with the fact that over the years, our easy access to antibiotics has allowed for the integrity of these beneficial biomes of bacteria to significantly wane (Kessler 2015). The United States has not been oblivious to this threat, and during the last 20 years, many approaches to antibiotic resistance have been suggested and weighted, specifically tackling the issue of overuse (Kessler 2015). The scientific and medical community alike can both conclude that there is a significant dilemma following the recent introduction of “superbugs”, which are antibiotic resistant bacteria that have been proven to be invincible against any type of antiviral or antibiotic (Kessler 2015). If not already alarming, “superbugs” are killing roughly 23,000 people in the United States each year, according to the CDC (Centers of Disease Control and Prevention) (Kessler 2015).
Dr. Blaser explains that in simplest terms, lack of punctiliousness of healthcare professionals has allowed for the selection of bacteria that are resistant to antibiotics. By giving our bodies antibiotics, the bacteria that are part of the beneficial “microbiome” are being eradicated (Kessler 2015). These bacteria contribute to our general wellbeing by supporting our immunity and countering against harmful bacteria (Kessler 2015). Dr. Blaser argues explicitly that if medical professionals only prescribed antibiotics for more serious ailments like pneumonias and meningitis and not for runny noses and sinusitis, the problem would not be widespread (Kessler 2015). Overuse of antibiotics, although a critical factor in the overall waning of antibiotics efficacy, is not the sole reason. Rather, the evolutionary changes in microbial DNA have manifested in an alarming manner that has also caused challenges for healthcare professionals (Babic and Bonomo 2009, 65-74). Mutations in genomic DNA are evolutionary changes that have both positive and negative effects. Not all mutations are disadvantageous, these slight changes in genomic DNA contribute to genetic diversity that is essential for evolution (Babic and Bonomo 2009, 65-74). However, this is highly dependent on the nature of the mutation and what the mutation causes. Genetic information in our DNA is an “instruction guide” for the production of proteins and enzymes that are responsible for development and vital biological reactions (Babic and Bonomo 2009, 65-74). A mutation is only harmful if it negatively affects the structure of a protein that is essential for development and function (Babic and Bonomo 2009, 65-74). Bacterial populations that are proven to be antibiotic resistant have acquired advantageous mutations which have allowed for their survival (Babic and Bonomo 2009, 65-74).
Missense mutations are the type of mutations that are responsible for allowing resistance, since they cause a single change in the coding of a single amino acid that is responsible for the integrity of the tertiary structure of the protein (Babic and Bonomo 2009, 65-74). In simplest terms, a single error in the reading of DNA when encoding for proteins can change the biological function of a bacterial protein (Babic and Bonomo 2009, 65-74). Normally, when pharmaceutical companies manufacture drugs that combat and target certain bacteria, it is especially important that a vital biological marker that is essential for the survival of the bacterium is recognized and targeted (Babic and Bonomo 2009, 65-74). When mutations like missense happen, this gives way for resistance because now the drugs are incapable of weakening or destroying the bacteria (Babic and Bonomo 2009, 65-74). The antibiotic resistant predicament is a difficult situation due to the presence of microorganisms with a high rate of mutagenesis which have resulted in excellent survival adaptation mechanisms (Babic and Bonomo 2009, 65-74). Before pharmaceutical companies manufacture effective antimicrobial drugs, multiple tests are run and the microbial genome is studied (Babic and Bonomo 2009, 65-74). Most importantly, the rate of the microbial mutation is noted and dealt with high significance because the vitality of the drug may be weakened if the organism is observed to have a high mutation rate (Babic and Bonomo 2009, 65-74).
So why are these organisms, notably bacteria, so prone to a high mutation rate? As mentioned earlier, microorganisms like bacteria have exceptional survival mechanisms. In times of stress and sudden environmental changes, certain bacteria will be selected to undergo mutagenesis in order to survive (Babic and Bonomo 2009, 65-74). In this way the changes in bacterial DNA are beneficial, and bacterial replication of species with the advantageous trait are naturally selected (Babic and Bonomo 2009, 65-74). In terms stated more simply, the intrinsic nature of bacteria to mutate readily when faced with a challenging environment (drug resistance) has made the mission to tackle antibiotic resistance arduous and unpredictable (Babic and Bonomo 2009, 65-74). It is important to note that most of the mutations a bacterium may experience will be lethal and not advantageous (Babic and Bonomo 2009, 65-74). So a drug that is manufactured to target species of bacteria will eradicate the majority of the population, but in essence will select for the resistant species (Babic and Bonomo 2009, 65-74). That is, as the rate of antibiotic administration increases, the chance of enabling and strengthening bacteria that is already resistant will only increase (Babic and Bonomo 2009, 65-74).
Scientists in the United States staunchly agree that antibiotic resistance will take more than just understanding mutations and the circumstances that facilitate their occurrence (Stephenson 2002, 2323-2452). Overuse of antibiotics and intrinsic biological mechanisms of survival have not been compelling enough in convincing the public (Stephenson 2002, 2323-2452). Yet, as onerous the topic may seem, over the years it only seems to be getting worse. As mentioned earlier, the threat of antibiotic resistance is troublesome because it is a multifactorial issue, and the obstacles should not solely be analyzed on a clinical note, but also from an economical and pharmaceutical stand point (O’Brien 2015, 168-172). Nationally in the last twenty years, as the prevalence of antibiotic resistant bacteria increases, the pressure to manufacture more potent and reliable drugs is now a priority discussion for pharmaceuticals (O’Brien 2015, 168-172). Although the approach may seem straightforward, it is not. The cost to make antibiotics is fairly cheap, but with the emergence of strenuous strands of bacteria being seemingly resistant, high costs of production, given the adverse circumstances, are making approaches difficult (O’Brien 2015, 168-172).
Regulatory agencies like the FDA (Food and Drug Adminstration), IDSA (Infectious Diseases Society of America) and CDC (Centers for Disease Control and Prevention) have all agreed that an immediate action from pharmaceutical companies is needed (Kuehn 2011, 78-93). The inaction has alarmed and worried officials due to slow production of antibiotics coupled with widespread resistance (Kuehn 2011, 78-93). Pharmaceutical recognize the threat but are reluctant, chiefly because drugs that are used to diagnose long-term chronic conditions are more lucrative and physicians are also more likely to use these drugs often due to the prevalence of chronic conditions (Kuehn 2011, 78-93).
The return in investment is therefore likely in a shorter period of time (Kuehn 2011, 78-93). This differs strictly with the market value of a potentially potent new antimicrobial drug, which would likely not be as profitable given its novelty and limited usage (Kuehn 2011, 78-93). Pharmaceutical companies are under extreme pressure to bring about solutions given the high incident rate of hospital borne infections in inpatient settings (Stephenson 2002, 2323-2452). Lack of infection control is mostly to blame (O’Brien 2015, 168-172). Lack of collaboration with other proponents in favor of an immediate and prudent execution plan is also part of the problem (O’Brien 2015, 168-172). As mentioned previously, the urge to manufacture and test drugs that are responsible for combatting resistant strains are also met with extreme caution (O’Brien 2015, 168-172).
Meaning, the function, safety and the effectiveness must be carefully considered and specific so that it is only used in serious, more complex cases (O’Brien 2015, 168-172). Developing new antibiotics needs a cohesive business model that “balances reasonable reimbursement with appropriate use” (O’Brien 2015, 168-172). Economically, pharmaceutical companies must find the most efficient way in making new antibiotics and before anything is approved, a business model is proposed (O’Brien 2015, 168-172). The question is, does it work in a way that reduces cost and increases efficacy (O’Brien 2015, 168-172)? The drive for production of new antibiotics has been curbed by escalating costs of lengthy clinical trials and the negative investment return resulting from low sale volume (O’Brien 2015, 168-172). At the same time, pharmaceutical companies are eager to impose market regulations to “protect antibiotics as a valuable source that may be subjected to overuse” (O’Brien 2015, 168-172). The factors that allow for antibiotic resistance may seem convincing enough but not everyone is persuaded that these circumstances have definitely caused antibiotic resistance. Although the solution to this problem requires cooperation from multiple players, there is some disagreement on who is responsible (McCullough et al 2015, 2465-2473). Given there is some substantial evidence suggesting overuse of antibiotics as contributing to antimicrobial resistance due to reckless use by healthcare professionals, numerous clinicians doubt this claim (McCullough et al, 2015, 2465-2473).
In fact, interestingly enough, many healthcare professionals have reason to believe that underuse of antibiotics may be responsible (McCullough et al, 2015, 2465-2473). Roughly 80% of clinicians think that they are not to blame for the resistance epidemic but in fact that others, especially patients should be held accountable (McCullough et al, 2015, 2465-2473). Clinicians claim that antibiotics are prescribed but whether or not patients comply with taking antibiotics regularly, is beyond their control (McCullough 2015 et al, 2465-2473). This may be a way for healthcare professionals to divert responsibility, but if this was the case, and patients are to blame for resistance, then clinicians are neglecting the fact that patients are subject to instruction by their healthcare provider (Kessler 2015).
Healthcare professionals assume a general responsibility to educate their patients on the medication that is prescribed (Kessler 2015). Physicians also have the authority to limit or increase the dose or even the necessity of the antibiotic if the patient is unresponsive towards the medication (Kessler 2015). Patients frequently see their healthcare provider when they get sick or are in need for a referral elsewhere (Kessler 2015).
Therefore, the claim that clinicians may not be responsible for antibiotic resistance, although fairly controversial, seems questionable. In the United States over the last 20 years antibiotic resistance has been a threat to modern medicine due to the overuse of antibiotics, evolutionary mechanisms of microbial DNA and pharmaceutical complications of producing new antibiotics. The next few years will be extremely critical in establishing right course of action for overcoming the crisis of antibiotic resistance (Kessler 2015). The United States has recognized apparent flaws in clinical settings and economic impediments that are discouraging industries such as pharmaceuticals from bringing a solution forward (Kessler 2015). As discussed, natural biological mechanisms such as mutations also complicate the fight against resistance (Babic and Bonomo 2009, 65-74). For this reason, antibiotic resistance strains continue to flourish and cause untreatable infections and multiple deaths (Babic and Bonomo 2009, 65-74). Indeed, the healthcare industry will continue to face the threat of antimicrobial resistance if an effective cooperative approach, which can successfully be implemented in inpatient and outpatient settings, is not discussed soon (Kessler 2015).
