💊 Antibiotic Resistance

Mutations arise spontaneously during DNA replication at a rate of roughly 10⁻⁹ to 10⁻⁷ per base pair per generation. In a large population of 10⁸ bacteria, statistically at least one cell will already carry a point mutation conferring resistance before any drug is administered. Horizontal gene transfer via plasmids can also spread pre-existing resistance genes between unrelated species almost instantaneously.

Bacteriostatic drugs halt bacterial growth without killing cells; bactericidal drugs actively kill bacteria. Most resistance models in this simulation assume a bactericidal mechanism where cells above the MIC are killed at a rate proportional to drug concentration. Bacteriostatic drugs require a functioning immune system to clear the halted population, so the outcome after stopping treatment can differ markedly from the bactericidal case.

Higher mutation rates increase the probability that a resistant mutant arises early, but they also generate harmful mutations across the genome, reducing average fitness. The interplay produces an optimal mutation rate — too low and no resistance emerges; too high and the population collapses from mutational load. This is the basis of "lethal mutagenesis" strategies that intentionally drive mutation rates beyond the error threshold to kill pathogens.

AMR refers to the ability of microorganisms — bacteria, viruses, fungi, and parasites — to resist the drugs designed to kill them. The WHO estimates that drug-resistant infections directly caused 1.27 million deaths in 2019 and contributed to nearly 5 million more. Without coordinated action on antibiotic stewardship, agricultural use, and novel drug development, AMR could cost the global economy trillions of dollars annually by 2050.

Reversibility depends on the fitness cost of resistance. If resistant bacteria grow significantly slower without antibiotics, susceptible wild-type cells can outcompete them over time when drug pressure is removed — a principle behind "antibiotic cycling" strategies in hospitals. However, if compensatory mutations arise that restore growth rate while maintaining resistance, or if the resistance gene spreads to the chromosome from a plasmid, reversal becomes very unlikely.

Larger populations harbour more pre-existing mutants by chance: a colony of 10⁹ cells is almost certain to already contain cells resistant to any single drug at typical mutation rates. This is why combination therapy — using two or three antibiotics simultaneously — is standard for infections like tuberculosis, since the probability of a single cell spontaneously carrying resistance to all drugs at once is vanishingly small (roughly 10⁻¹⁸).

Infection control measures include antibiotic stewardship programmes that restrict broad-spectrum drugs to confirmed resistant infections, hand hygiene protocols, isolation of MRSA-positive patients, and surveillance cultures. Antibiotic stewardship has been shown to cut resistance rates by 20–30% in some clinical settings while also reducing costs by eliminating unnecessary prescriptions.

Superbugs are bacteria resistant to multiple, or in some cases nearly all, available antibiotics. The WHO's critical-priority pathogens include carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. Carbapenem antibiotics are considered last-resort drugs, so resistance to them leaves clinicians with very few treatment options — often only the older drug colistin, which carries significant kidney toxicity.