The Global Fight Against Antimicrobial Resistance Gets A Local Boost in Pulaski, Tennessee

The sixth event in the inaugural Microbiology, Public Health, and History film festival at University of Tennessee, Southern (formerly Martin Methodist College) was held on the evening of Mar 23, 2023. The aim of this festival, sponsored by the American Society for Microbiology’s (ASM) Science Festivals Grants program, is to examine important topics in infectious diseases using the medium of film from three different perspectives: microbiology, public health, and history.

The theme for the sixth event, entitled The Silent Pandemic, was antimicrobial resistance. The event was held in the Gault Fine Arts Center on the UT Southern campus in Pulaski. The highlight of the evening was the Tennessee-wide première of the 2022 documentary, Silent Pandemic – The Global Fight Against Antibiotic Resistance (German: Stille Pandemie – Der globale Kampf gegen Antibiotika-Resisten). This screening was kindly sponsored by the Antimicrobial Resistance Fighters Coalition (ARFC), which allowed UT Southern students and members of the local community an opportunity to see this important film for free.

Directed by Michael Wech, Silent Pandemic is the follow-up to Wech’s 2019 work, Resistance Fighters – The Global Antibiotics Crisis (German: Resistance Fighters – Die globale Antibiotika-Krise). Just over 30 people were in attendance, most of whom were UT Southern undergraduates. Some participants chose to attend in person while many took advantage of the ability to attend online using Zoom, a necessity for a rural campus with many non-residential students.

(Image Left: Dr. Scott Hileman discusses the impact and history of penicillin during WWII)

The evening began with a brief presentation by Dr. Scott Hileman of Coastal Carolina University on World War II and the coincident antibiotic miracle”. Dr. Hileman, a military historian, described the development of penicillin into a key antibacterial medicine (antibiotic) by the Allies, focusing on critical American innovations towards mass producing the world’s first naturally derived antibiotic. Mass production proved a seemingly insurmountable challenge until Oxford University scientists were introduced to deep-tank fermentation by US Department of Agriculture scientists. The successful production of penicillin at industrial scales not only impacted the Allied war effort, but also heralded major changes for humans at large. For example, minor cuts and scrapes once resulted in death with such frequency before antibiotics became widely available that family portraits often included deceased children; the advent of antibiotic medication meant that such injuries were no longer life-threatening. Dr. Hileman also highlighted the intriguing possibility that penicillin smuggled by Hitler’s personal doctor, Theodore Morell, may have saved the German leader’s life following an assassination attempt in July 1944.

(Image Right: Dr. Scott Hileman discusses the impact and history of penicillin during WWII)

Dr. Hileman also examined the impact of sulfa (a.k.a. sulpha) drugs, the first antibacterial medication to achieve widespread clinical use and which were available to both sides in the war. Gerhard Domagk’s discovery of sulfonamidochrysoidine in 1935 marked the first major success in the clinician’s war against bacterial infection, although this achievement is often overlooked in penicillin’s wake. Despite their side effects, sulfa drugs became very widely used, frivolously in many instances. Reports of resistant infections became widespread during WWII, an ominous nightingale warning us of the limited lifespan of the antibiotic miracle.

Dr. Hileman’s presentation provided an excellent prelude for Silent Pandemic. The 90-minute documentary highlights a global crisis that is not new. The first report of clinical antimicrobial resistance (AMR), towards salvarsan, was published in 1928, before both sulfa drugs and penicillin became available. Since 1928, the clinical introduction of every antimicrobial drug since has been followed within a few years by clinical reports of resistant infections. Despite this well-documented phenomenon, the world blithely continued introducing new and modified antimicrobial drugs until the pipeline began to dry up. Despite the looming apocalypse, the World Health Organization (WHO) only started using the term silent pandemic” to refer to the AMR crisis in 2021.

The US Centers for Disease Control (CDC) estimates that 2.8 million AMR infections occur each year in the USA alone. Worldwide, an estimated 5 million deaths each year are associated with resistant bacteria, including 1.3 million directly attributed to such bacteria (Antimicrobial Resistance Collaborators, 2022). By 2050, 10 million people may die each year because of resistant bacteria alone. Although mostly associated with antibacterial drugs, the AMR phenomenon also involves antifungals, antiprotozoals, and antivirals. Despite the AMR crisis dwarfing the burden of even tuberculosis (1.6 million deaths worldwide per year), the film avoids doomsday predictions. Instead, it adopts a tone of cautious optimism. Silent Pandemic focuses on different facets of the AMR problem, examining root causes, and exploring potential solutions. The AMR crisis may be alarming but the audience is challenged to act rather than panic.

Most of the students in attendance had either taken or were taking a course in microbiology; some were taking epidemiology. Most aspired to careers in medicine and allied health in the future. Although most had learnt about antibiotic resistance, at least in theory, their ability to describe and explain the features, causes, and management of the crisis varies widely. Moreover, they were even less familiar with the situation overseas. By showing different facets of the AMR crisis, ranging from familiar developed country settings to less familiar developing world situations, the film helped informed these future healthcare professionals who will be crucial to managing the misuse of antimicrobial drugs.

The rate at which microorganisms acquire resistance to antimicrobial drugs had already outpaced the rate at which new antimicrobial medications were being introduced prior to the COVID-19 pandemic. Improper prescription and misuse of antimicrobials during the pandemic has only worsened the crisis by promoting the spread of resistance. In industrialized countries, antimicrobial use among humans is regulated but such drugs are still often prescribed unnecessarily. The film illustrates the need to curb unnecessary usage by introducing us to the antibiotic-resistant bacterium Clostridium difficile, which threatened the life of an American woman who had been consuming the average amount of antibiotics for Americans” her whole life, often without demonstrated cause.

The need for fast and accurate diagnostics to identify patients with microbial infections is rammed home by the tragic case of a German girl who underwent multiple amputations following a meningococcal infection that took more than a week to be diagnosed. To try and combat the spread of antibiotic-resistant bacteria in hospitals, the film takes us inside Duke University Medical Center, one of the country’s leading hospitals, to learn how infection control specialists are reinforcing the old adage that prevention is better than cure” (Erasmus) and helping manage antibiotic usage to slow the rate at which resistant bacteria arise and propagate.

In contrast to these somewhat familiar scenarios, the film also showcases eye-opening scenes shot in developing countries that many in the audience had never experienced. Sales of antimicrobial drugs in many developing countries do not require a prescription; even if a prescription is required, the prescriptions are often improperly written. Easily accessible antibiotics that patients can purchase in small amounts with what money they have available can save lives when low doctor-to-patient ratios make it impossible to see a clinician when one needs to. In fact, the availability of cheap antibiotics is often critical to citizens not missing work and earning a day’s wages to put food on the table with.

Crucially, the audience learnt that there can be no one-size-fits-all approach to dealing with the AMR crisis. The nature of the problem differs in a resource-rich versus a resource-poor environment. Where advanced diagnostics and regulation of both prescription and sale can help mitigate antimicrobial misuse in industrialized countries, developing countries could benefit more greatly from improvements in sanitation and civil infrastructure that would reduce the incidence of microbial infection and the need to consume antimicrobial drugs.

Another point emphasized by the film is the interconnected nature of the world that we live in. Transport networks deliver people and goods around the clock to meet the demands of the global capitalist economy. Most of the food and agricultural products that we consume is supplied by a relatively small number of producers. The use of antimicrobial compounds in agriculture is less regulated than in medicine, and overuse has led to many of these becoming useless for treating patients. Agricultural overuse can rapidly select for resistant microbes; modern international trade disperse can subsequently disperse resistant microbes around the globe. For example, the film highlights Dutch tulip bulbs bearing azole-resistant fungi that caused serious respiratory infections at home. However, as the largest global supplier of flowers, the Netherlands shipped these bulbs to many countries where similar, difficult-to-treat infections subsequently arose.

(Image Right: Dutch tulip fields, the unsuspecting carriers of azole-resistant fungi.)

Animal farming also poses significant challenges, especially with rising consumer demand for meat as incomes rise in the developing world. Overcrowding of animals in modern large-scale farming to increase productivity paradoxically increases the incidence of disease. Farmers compensate by including antibiotics in feed to prevent disease outbreaks. Such antibiotics are often excreted by animals unchanged. Thus, modern farms provide ideal breeding grounds for resistant microorganisms. Clearly, it will take more than just clinical and public health professionals working together to solve the antimicrobial issue in agriculture.

The film ends on an optimistic note, reminding us of an adage attributed to Erasmus in the early 16th century: prevention is better than cure”. Vaccination against typhoid fever was key to bringing a 2018 outbreak of extensively drug-resistant Salmonella enterica serovar Typhi in Pakistan under control. Moreover, this outbreak stemmed from the poor quality of local drinking water and the lack of sewage treatment facilities. Another hopeful development is Perdue Farms’ commitment to zero antibiotic use in their poultry operations, a move instigated by consumer demand. Bell & Evans and Tyson have since done the same, although the cattle industry has yet to change its practices significantly.

The film does not offer easy solutions because there are none. The dearth of support and funding for the discovery and development of new antibacterial drugs is highlighted early on but there is little hope of the free market solving this problem on its own. Instead, significant partnerships between government, industry, and non-profit sectors will be needed. Even if new drugs do come down the pipeline, we must be prepared for resistance to be on hot on their heels if their use is not managed. Alternative, non-antibiotic strategies are needed to find new ways to treat microbial infections.

After the film’s conclusion, the audience was invited to join in a panel discussion featuring three invited speakers. Via Zoom, they were provided a unique opportunity to hear from experts on the topic of AMR located all over the country and in other parts of the world. The panelists who joined us were Dr. Jillian Socea, a post-doctoral fellow in a public health laboratory in Nashville, Tennessee; Dr. Ashley Styczinski, a medical officer at the US Centers for Disease Control (CDC) and adjunct clinical professor at Stanford University; and Dr. Tanya Sysoeva, an assistant professor at the University of Alabama in Huntsville (UAH). A fourth panelist, Prof. Muhammad Usman Qamar of Government College University in Faisalabad, Pakistan was unable to join due to technical problems.

The panel members drew on their respective areas of expertise and their unique experiences to answer questions from the audience and address issues raised by the film. Specifically, Dr. Socea evaluates clinical diagnostic tools and platforms and has experience tracking antimicrobial resistance in clinical isolates. Dr. Styczinski has a wealth of global health experience, having worked on perinatal transmission of antimicrobial in Bangladesh and experienced the difficulties associated with managing antimicrobial resistance in developing regions. Lastly, Dr. Sysoeva is a chemist and microbiologist who has studied antibiotic resistance mechanisms in bacteria. Her lab studies multidrug-resistant urinary tract infections as well as the microbes that live in the human genitourinary tract.

Among the key issues addressed was what could be done to jumpstart the development of new antimicrobial drugs, particularly antibacterial drugs. The high cost of clinical trials prevents small companies willing to find or synthesize new antibiotics from carrying development to the finish line. The narrow profit margins combined with the high rate of failure in clinical trials makes antibiotic development a less than appetizing endeavor for large pharmaceutical companies. Given that this is a problem that capitalistic approaches cannot solve, partnerships involving government, non-profit organizations, academia, and industry will be necessary. The panel offered some hope in the form of leadership by the government of Great Britain, which has begun to offer contracts for new antibiotic development.

Another key issue was what could be done to help improve the AMR situation in developing countries. Although organizations such as the Fleming Fund support low- and middle-income countries to act against AMR, the help that they offer does not always take into consideration the logistical challenges that such countries face. A high-tech diagnostic tool designed for use in First World settings costs more to operate in a developing country due to import duties and transport costs. Moreover, patients may never get to see a doctor due to distance, expense, and long wait times. Resource-rich countries, however, cannot afford to focus solely on managing AMR within their own borders. The failure to solve the AMR issue at the source increases the risk that AMR microorganisms will be exported via international travel and trade to other countries, exacerbating the silent pandemic.

In tune with the cautiously optimistic tone of Silent Pandemic, the panel also explored possible alternative strategies to treat bacterial infections, including probiotic consumption and phage therapy. Other promising ideas involve disrupting communication between microbial cells and blocking their ability to activate virulence mechanisms on or within a host. Although the audience was keen to learn about high-tech approaches such as genetic engineering of microorganisms to slow down the acquisition of mutations and genetic elements that promote antimicrobial resistance, Dr. Styczinski pointed out that several tools already exist in our antimicrobial arsenal that can reduce antimicrobial drug use. For instance, vaccines bacterial diseases as well as vaccines against viral diseases, such as influenza, are currently underutilized. Greater vaccine coverage will reduce the need to use antimicrobial drugs.

The evening closed with a question from a student about what we, as individuals, can do to help combat AMR. This question provided the perfect way to end the evening given the mission of the ARFC. The panelists offered their opinions on meaningful action. Simply staying home when one is ill and not pressuring doctors to prescribe antibiotics when there is no compelling need will make a difference. Consumer pressure can help rein in excessive and unnecessary antimicrobial usage in agriculture where regulatory action is either lacking or lagging. Staying up to date on vaccinations too is a small but meaningful step in the right direction.

Think global, act local. Together, we can mitigate the impact of AMR. 

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