Antibiotics and antibiotic resistance

Until the mid twentieth century, bacterial infections were a leading cause of death. A cut that became infected, pneumonia, childbirth or a simple operation could be fatal. Diseases such as tuberculosis and syphilis had no reliable cure.

In 1928 Alexander Fleming noticed that a mould, Penicillium, had killed bacteria growing on a culture dish in his London laboratory. Turning this observation into a medicine took more than a decade. Howard Florey, Ernst Chain and their team at Oxford purified penicillin and showed it could cure infections, and it was mass-produced during the Second World War.

• Some, like penicillin, stop bacteria building their cell walls, so the cells burst.
• Some block the ribosomes bacteria use to make proteins.
• Some interfere with the copying of bacterial DNA.
• Some block metabolic pathways bacteria need but human cells do not use.
• Antibiotics target features of bacteria, which is why they do not work against viruses such as those causing colds and flu.

Bacteria reproduce quickly, sometimes dividing every 20 minutes, and random genetic mutations occur as they do. Occasionally a mutation helps a bacterium survive an antibiotic, perhaps by pumping the drug out, breaking it down or changing the target it attacks.

When antibiotics are used, susceptible bacteria die, but resistant ones survive and multiply. This is natural selection happening in real time. Bacteria can also pass resistance genes to one another, even between different species, on small loops of DNA called plasmids, which lets resistance spread rapidly.

Any antibiotic use can select for resistance, but unnecessary use accelerates it. Antibiotics are often prescribed for viral infections they cannot treat. In some countries they are sold without prescription, and in agriculture they have been widely given to healthy animals to promote growth or prevent disease.

Poor sanitation, crowded hospitals and inadequate infection control help resistant bacteria spread between people. Global travel carries resistant strains across borders quickly.

Some bacteria now resist most or all available antibiotics. Examples include methicillin-resistant Staphylococcus aureus, known as MRSA, drug-resistant tuberculosis and resistant forms of the bacteria behind gonorrhoea. A major study published in The Lancet estimated that bacterial antimicrobial resistance was directly responsible for more than a million deaths in 2019.

Resistance also threatens much of modern medicine. Surgery, cancer chemotherapy, organ transplants and care for premature babies all rely on antibiotics to prevent or treat infections. Meanwhile, few new classes of antibiotics have been discovered in recent decades, partly because developing them is scientifically hard and commercially unattractive.

Doctors and health systems practise antibiotic stewardship: prescribing antibiotics only when needed, choosing the right drug and duration, and using tests to identify infections. Vaccines reduce infections and therefore antibiotic use, and good hygiene and infection control in hospitals slow the spread of resistant bacteria.

Individuals can help by not demanding antibiotics for colds or flu, taking antibiotics exactly as prescribed, never sharing or using leftover antibiotics, and keeping vaccinations up to date. Researchers are exploring new antibiotics, bacteriophage viruses that infect bacteria, and new funding models to encourage drug development.