A Brief History of Antibiotics — and Resistance

Before antibiotics

Within living memory, a scratch could kill. Before the 1940s, bacterial pneumonia, tuberculosis and infected wounds were leading causes of death; around one woman in every few hundred births died of childbed fever, and a simple ear infection could spread to the brain. Medicine could comfort, but often could not cure.

The discovery that changed everything

In September 1928, Alexander Fleming returned from holiday to his laboratory at St Mary's Hospital, London, and noticed that a stray mould (Penicillium) had contaminated a culture plate of staphylococci — and that the bacteria around it had been destroyed. He named the active substance penicillin. It took a decade more, and the work of Howard Florey, Ernst Chain and Norman Heatley at Oxford, to purify it and prove it could cure infections; wartime industrial effort then scaled production, and by 1945 penicillin was saving thousands of lives.

“The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” — Alexander Fleming, Nobel Prize lecture, 1945

Fleming's warning was already coming true as he spoke: penicillin-resistant staphylococci had been observed in hospitals by the early 1940s, within a few years of the drug's first clinical use. The pattern — new drug, then resistance within years — has repeated with essentially every antibiotic since.

Timeline: an arms race in fast forward

• 1928 Fleming discovers penicillin.
• 1940–45 Penicillin purified, mass-produced and deployed in the Second World War. First penicillin-resistant Staphylococcus aureus observed within the decade.
• 1945 Fleming warns of resistance in his Nobel lecture.
• 1943–1962 The “golden age” of discovery: streptomycin (1943), tetracycline, chloramphenicol, erythromycin, vancomycin, methicillin and more — most of today's antibiotic classes are found in these two decades.
• 1961 Methicillin-resistant S. aureus (MRSA) reported in England — two years after methicillin's introduction.
• 1960s–70s Antibiotics become routine in livestock farming, including as growth promoters. Resistance genes begin circulating between farm animals, food and people.
• 1987 The last entirely new class of antibiotics to reach patients for decades is discovered. The discovery pipeline then largely dries up as big pharmaceutical companies exit the field.
• 1988 Vancomycin-resistant enterococci (VRE) identified — resistance to a key “last resort” drug.
• 2008 NDM-1, an enzyme conferring resistance to carbapenems, identified; it spreads worldwide within a few years.
• 2015 The mcr-1 gene, defeating the last-line antibiotic colistin, reported in China and soon found globally. WHO launches its Global Action Plan on AMR.
• 2016 & 2024 UN General Assembly holds high-level meetings on AMR; in 2024 world leaders adopt the first concrete global target — cutting AMR deaths 10% by 2030.

The discovery drought

Between the 1940s and 1960s, researchers found most of the antibiotic classes we still rely on today, largely by screening soil microbes. Since the late 1980s, no major new class reached the clinic for over three decades; nearly all “new” antibiotics approved since have been variations on old classes, which resistance can often adapt to quickly. (The first genuinely new-class approvals in decades have only begun to appear in the mid-2020s — see the Innovation page.)

The reasons are economic as much as scientific. A new antibiotic should be used as little as possible to preserve it, which means low sales precisely because the drug is valuable. Developing one costs on the order of a billion dollars, yet most small antibiotic companies have struggled or gone bankrupt even after approval. Most large pharmaceutical companies left antibiotic research decades ago. The result: bacteria evolve in minutes, while our replacement pipeline moves in decades — an arms race we have been losing by default.

Sources for this page

• Fleming, A., “Penicillin”, Nobel Lecture, 11 December 1945 — nobelprize.org
• “Antibiotics re-booted — time to kick back against drug resistance”, npj Antimicrobials and Resistance, 2025 — nature.com/articles/s44259-025-00096-1
• CDC, “Antimicrobial Resistance Threats” reports — cdc.gov/antimicrobial-resistance
• WHO, “Global Action Plan on Antimicrobial Resistance”, 2015 — who.int