Antimicrobial Resistance and Selection Pressure

Antibiotic selection pressure is the environmental filtering created when an antibiotic suppresses susceptible bacteria but allows resistant variants to survive. It drives antimicrobial resistance by changing the composition of a bacterial population, rather than by purposefully creating resistance in individual bacteria.

Variation on which selection acts

A bacterial population may contain resistance because of random genetic changes or because some cells have acquired resistance genes. Antibiotic exposure then operates through natural selection on this heritable variation.

• Resistance may arise through a random chromosomal mutation that changes the drug target, drug uptake or another relevant cellular function.
• Bacteria may obtain resistance genes through horizontal gene transfer, often on plasmids or other mobile genetic elements.
• Antibiotics do not direct bacteria to develop a needed mutation; they preferentially remove susceptible competitors.

Selection, survival and spread

At a given antibiotic concentration, resistant cells have a relative fitness advantage because susceptible cells are killed or their growth is inhibited. Survivors multiply and pass resistance vertically to their descendants, increasing its frequency in the population.

• Repeated or unnecessary exposure repeatedly favours resistant lineages and can make them dominant.
• Resistance genes can spread between bacteria through conjugation, transformation or transduction, including across some species boundaries.
• Drug gradients within patients or environments may permit partially resistant variants to survive and undergo further selection.
• Antibiotic use can also select resistant commensal bacteria, which may serve as reservoirs of resistance genes.

Reducing selection pressure

The objective is not to eliminate necessary antibiotic use but to reduce avoidable exposure and bacterial transmission through antimicrobial stewardship and public-health measures.

• Antibiotics should be used only when indicated, with an appropriate drug, dose and duration guided by diagnosis wherever feasible.
• Vaccination, sanitation and infection prevention reduce infections and therefore the need for antibiotics.
• Surveillance and a One Health approach address selection and transmission across humans, animals and the environment.