Antibiotic Resistance
The drugs that transformed 20th-century medicine are failing faster than we're replacing them — and routine surgery is among the things at risk.
The short version
- Antibiotic-resistant infections killed approximately 1.27 million people in 2019 — more than HIV/AIDS or malaria — and the WHO considers antimicrobial resistance one of the greatest threats to global health.
- Resistance is an inevitable biological consequence of antibiotic use; the problem is that we are accelerating it by overusing antibiotics in human medicine and using them in massive quantities in livestock agriculture as growth promoters.
- The pharmaceutical pipeline is nearly dry: no major new class of antibiotics has been approved since 1987, because the economics of antibiotic development are structurally broken — antibiotics are cheap, used briefly, and deliberately rationed, making them poor business investments.
- Without effective antibiotics, the modern medical infrastructure — organ transplants, cancer chemotherapy, joint replacement surgery, premature neonatal care — becomes dramatically more dangerous or impossible.
What it is
Antibiotics are compounds that kill or inhibit the growth of bacteria — either by destroying their cell walls, interfering with protein synthesis, disrupting their DNA replication, or blocking other essential metabolic processes. The antibiotic era began with Alexander Fleming's discovery of penicillin in 1928 and its subsequent development by Howard Florey and Ernst Chain. Within two decades, penicillin, streptomycin, chloramphenicol, and other antibiotics had transformed medicine: infections that had been reliably fatal — streptococcal pneumonia, bacterial meningitis, tuberculosis, syphilis — became treatable. Childhood mortality from bacterial infections fell dramatically. Surgical procedures, childbirth, and cancer treatment became safer because the bacterial infections that followed them became manageable. Antibiotics are among the most consequential medical discoveries in human history.
Antibiotic resistance occurs when bacteria evolve mechanisms to survive exposure to drugs designed to kill them. This is not a malfunction of the drugs — it is evolution operating exactly as it should. Random genetic mutations occur constantly in bacterial populations; mutations that allow survival in the presence of an antibiotic are selected for rapidly because bacteria reproduce in hours and populations number in billions. Once resistance evolves, it spreads not just through bacterial reproduction but through horizontal gene transfer — bacteria sharing resistance genes across species through plasmids, small circular DNA molecules that can jump between unrelated bacterial strains. A resistance gene that evolves in one organism can spread to others in the same environment. The presence of antibiotics accelerates this selection by killing susceptible bacteria while allowing resistant ones to thrive and reproduce without competition.
Human antibiotic overuse is a major driver of resistance. Antibiotics are frequently prescribed for viral infections — colds, influenza, COVID-19 — against which they have no effect, but which expose the patient's microbial ecosystem to selective pressure that encourages resistance. A 2018 study estimated that approximately 30% of antibiotics prescribed in U.S. outpatient settings were unnecessary. Hospital-acquired infections, often caused by resistant organisms like MRSA (methicillin-resistant Staphylococcus aureus), C. difficile, and carbapenem-resistant Enterobacteriaceae, have become a major source of morbidity and mortality in healthcare settings. But the largest use of antibiotics globally is not in human medicine — it is in livestock agriculture, where antibiotics have been administered at sub-therapeutic doses to food animals (primarily poultry, pigs, and cattle) not to treat disease but to promote faster growth and compensate for the crowded, stressful conditions of industrial animal agriculture. The FDA estimates that approximately 70% of medically important antibiotics sold in the United States are sold for veterinary use.
The pipeline problem is distinct from the overuse problem and in some ways harder to solve. Developing a new antibiotic costs approximately $1–1.5 billion and takes 10–15 years from discovery to approval. Once approved, new antibiotics are deliberately rationed — held in reserve for cases where other drugs have failed — to slow the development of resistance to the new drug. This means a new antibiotic generates modest revenue for a few years before resistance inevitably begins to emerge, after which it may be used more broadly. The financial return on antibiotic development is therefore poor relative to drugs for chronic conditions taken by patients indefinitely. Major pharmaceutical companies — Pfizer, Sanofi, AstraZeneca, and others — have exited the antibiotic market over the past decade. The remaining pipeline consists primarily of modifications of existing drug classes rather than truly new mechanisms of action, and it is inadequate to address the resistance organisms already emerging globally.
Why it matters
The magnitude of the current death toll from antibiotic-resistant infections is not widely understood. A 2022 study in The Lancet, analyzing data from 204 countries, estimated that 1.27 million deaths were directly attributable to antibiotic-resistant infections in 2019 — a figure larger than the annual death toll from HIV/AIDS or malaria. An additional 4.95 million deaths were associated with antibiotic-resistant infections, meaning the infection contributed to but was not the sole cause of death. Lower respiratory infections caused by resistant organisms were the leading contributor. The Global Burden of Disease analysis projects that without effective intervention, deaths attributable to antimicrobial resistance could reach 10 million per year by 2050 — at which point resistance would surpass cancer as a cause of death globally.
The medical infrastructure of modern medicine rests on the assumption that bacterial infections are treatable. Organ transplant recipients receive immunosuppression that leaves them vulnerable to infection — manageable only with effective antibiotics. Cancer chemotherapy destroys immune cell populations, leaving patients dependent on antibiotics to survive the treatment that might cure them. Joint replacements and cardiac surgery create surfaces where bacteria can colonize; the success of these procedures depends on antibiotic prophylaxis. Premature infants in neonatal intensive care units are susceptible to infections that antibiotics routinely control. If resistance renders these antibiotics ineffective, these procedures become dramatically more dangerous or must be reconsidered entirely. Routine medicine as practiced in the 21st century is not separable from effective antibiotics.
The international governance problem is acute. Antibiotic resistance is a global commons problem: resistance that evolves in one country migrates globally through human travel, animal trade, and environmental spread. Prudent antibiotic stewardship in the United States is undermined by overuse in countries where antibiotics are available over the counter without prescription — as they are in many lower-income countries where they are also most needed. Low- and middle-income countries have among the highest burdens of infectious disease and the fewest resources for infection control. The WHO's Global Action Plan on Antimicrobial Resistance (2015) established a framework for national action plans, surveillance, and research coordination, but implementation has been uneven and underfunded. The 2024 UN General Assembly High-Level Meeting on AMR committed member states to reducing AMR-attributable deaths by 10% by 2030 — a modest target whose achievement requires infrastructure that many countries lack.
The structural economic failure of antibiotic development is a market failure in the technical economic sense: the social value of a new antibiotic far exceeds the private value a company can capture from it. Several policy mechanisms have been proposed to correct this. The PASTEUR Act in the U.S. Congress would create a subscription model for antibiotic reimbursement — paying pharmaceutical companies a fixed fee for developing and maintaining access to critical antibiotics, decoupled from the volume sold, to eliminate the incentive to oversell. The UK has piloted a similar model. These proposals exist; they have not been enacted at meaningful scale. The gap between the magnitude of the problem — a projected 10 million deaths per year by mid-century — and the urgency of the policy response is among the clearest cases of governance failure in contemporary public health.