In 2014, the World Health Organization (WHO) published its first report on antimicrobial resistance surveillance (AMR). This report highlighted the growing threat of bacteria resistant to modern medicine, which had already reached alarming levels in many parts of the world. Today, AMR has been linked to 5 million deaths per year globally, which is expected to double by 2050. In the US alone, antibiotic resistance caused an estimated 2.8 million infections and 35,000 deaths annually, according to data released by the CDC in 2019. AMR is present everywhere—in animals, foods, and plants—due to the broad overuse and misuse of antimicrobials, even in soil, water, and plants. If left unaddressed, the spread of AMR could make many bacterial pathogens even more lethal in the future than they already are today.
A Global Threat Spurred by Overuse and Misuse
Several international organizations have joined forces to develop a global action plan on AMR, including the WHO, the World Organization for Animal Health (WOAH), and the Food and Agriculture Organization of the United Nations (FAO). Improving global AMR surveillance is critical when developing global strategies, monitoring the effectiveness of public health interventions, and detecting new threats as they arise. The WHO has implemented the One Health approach, an integrated, unifying approach to balance and optimize the health of people, animals, and the environment. Under the One Health approach, government officials, researchers, and workers across local, national, regional, and global sectors work together to respond to health threats. These measures are intended to detect, prevent, and respond to global health threats like AMR.
In many developing countries, antimicrobial drugs are misused and in excess due to their easy acquisition—oftentimes even being available for purchase without a prescription. Additionally, even in developed countries, antibiotics are often incorrectly prescribed. The CDC estimates that at least 30% of antibiotics prescribed are unnecessary, meaning no antibiotic was needed. The same study found that about 44% of outpatient antibiotic prescriptions were written to treat patients with acute respiratory conditions, such as sinus infections, viral upper respiratory infections, and influenza. In these instances, approximately half of the antibiotics were unnecessarily prescribed.
Antibiotic Innovation is Currently High Risks and Low Rewards
The last antibiotic class to be successfully introduced was discovered in 1987. Because antibiotic development requires a high financial investment with a meager return, even if a company is deeply passionate about responding to the threat of AMR, a suitable business model still needs to be created to incentivize pharmaceutical companies to back innovation in the antimicrobial space. Developing one new antibiotic class can cost approximately $1 to 1.5 billion. Still, antibiotics are often deemed unprofitable because they are not prescribed in high volumes—as opposed to cancer or cardiovascular drugs. In addition to a high price tag, developing new antibiotics can take over 10 years. New drugs must undergo extensive testing; only a fraction of those therapeutics will make it through the entire drug development process. For the few new classes that get to market, prices for antibiotics are set quite low and sparingly prescribed. If misused, resistance can develop quickly, potentially invalidating a drug that may only have been on the market for a short time and resulting in low or limited profits for the developing company. All these factors combined have made antibiotic innovation a poor investment decision for most pharmaceutical companies.
Improving the Current Drug Development Landscape Through Regulations
The current business model must change to create more incentives for the substantial investment of time, money, and resources needed to develop new antibiotics and bring them to market. Because the majority of the costs associated with drug development occur in the preclinical phase, when there is no guarantee that a molecule will perform as expected, heavier reliability on artificial intelligence capabilities, such as extensive data analysis and machine learning, could be beneficial in speeding up the drug discovery process to predict which molecules are most likely to have the properties needed to advance to the final stages of efficacy, safety, and approval.
Legislative government bodies also can improve the current drug development landscape regarding antibiotic innovation. In the United States, the Pasteur Act, a bipartisan bill that has been introduced to Congress three times since 2019, would bolster drug development by creating a subscription-style business model in which the US government would offer upfront payments to drugmakers in exchange for responsible stewardship policies and unlimited access to their antibiotics. Antimicrobial stewardship policies have a 3-fold goal:
- To work with healthcare practitioners to guarantee every patient receives the most appropriate antimicrobial with the correct dose and duration.
- To prevent antimicrobial overuse, misuse, and abuse, both in the hospital and outpatient settings, ensure physicians only prescribe antibiotics when necessary.
- To minimize the development of resistance at the individual patient level and the community level.
Despite strong support from numerous organizations for the Pasteur Act to become law in the US, the Act is still politically gridlocked and has not moved forward. Legislation similar to the Pasteur Act has also been introduced in Europe. The Pharmaceutical Strategy for Europe initiative is intended to address several AMR challenges, including the lack of investment in antimicrobials and inappropriate use of antibiotics. While the plan details are still being sorted out, the strategy includes measures to promote the responsible use of antibiotics, which could help reduce antibiotic resistance rates and preserve existing antibiotics for extended periods. This could create a more favorable environment for developing new antibiotics, as they would be less likely to face resistance issues.
We Must Plan for the Future Today
If the COVID-19 outbreak taught us anything, we must be better prepared to respond to future pandemics through international cooperation and collaboration. The pandemic proved that diseases do not respect borders, and a global, joint response is necessary to control the spread. Additionally, by strengthening our primary healthcare systems, we can help detect outbreaks early on, provide timely treatment to patients, and prevent the spread of disease. However, unlike COVID-19, a viral pandemic, a bacterial pandemic today may not have a viable treatment. This is why antibiotic drug development needs to continue, with appropriate incentives and access plans implemented as quickly as possible.
Furthermore, measures that increase disease awareness and promote antibiotic stewardship must be adopted to prevent the rise of drug-resistant bacteria. Several public and private organizations worldwide are working to develop innovative treatment approaches aimed at outsmarting these superbugs. These organizations must have the tools, funds, and business model necessary to continue to push innovation in the antimicrobial space and prepare for the pandemic of tomorrow, today.