Antibiotics are medications designed to combat bacterial infections by either killing bacteria or stopping their growth. These drugs revolutionized medicine, treating and preventing once life-threatening illnesses. However, their widespread use has an unintended consequence: the selection of bacteria less susceptible to their effects, leading to concerns about antibiotic resistance.
Understanding Bacterial Selection by Antibiotics
Bacterial selection describes how antibiotics create an environment favoring the survival and multiplication of bacteria that withstand their effects. When an antibiotic is introduced, it acts as a selective pressure, eliminating susceptible bacteria from a population. This leaves behind bacteria with natural or acquired resistance mechanisms.
Surviving resistant bacteria then have less competition, reproducing more freely and increasing their proportion within the bacterial population. This shifts the bacterial landscape towards a higher prevalence of resistant strains. Even low concentrations of antibiotics can exert this selective pressure, influencing bacterial community composition over time. Their impact extends beyond eradicating infections, molding bacterial evolution.
The Spectrum of Selective Concentrations
Bacterial selection is not limited to antibiotic concentrations that kill bacteria outright. The Minimum Inhibitory Concentration (MIC) is the lowest concentration of an antimicrobial agent preventing visible microorganism growth after overnight incubation. It is widely used in laboratories to determine bacterial susceptibility.
However, selection can occur at much lower levels than the MIC. The Minimum Selective Concentration (MSC) is the lowest antibiotic concentration where resistant strains gain a competitive growth advantage over susceptible strains. MSCs can be hundreds of times lower than the MIC of susceptible bacteria, meaning trace amounts can promote resistance.
This concept leads to the “mutant selection window” (MSW), the range of antibiotic concentrations where resistant mutants are most efficiently selected. This window extends from the lowest concentration inhibiting susceptible bacteria (often near the MSC) up to the Mutant Prevention Concentration (MPC), which inhibits the least susceptible, single-step resistant mutants. Maintaining antibiotic concentrations outside this window—either well above the MPC to kill all bacteria or below the MSC to avoid selection—is a strategy to minimize resistance emergence.
Where Antibiotic Selection Occurs
Antibiotic concentrations driving bacterial selection are found in various environments. Clinical settings, like hospitals and outpatient clinics, are where patients receive therapeutic antibiotic doses. These drugs in the human body create direct selective pressure on bacterial populations, including infection-causing and commensal bacteria.
Beyond human medicine, agricultural antibiotic use also contributes to selection. Large quantities are used in livestock to prevent disease and promote growth, leading to resistant bacteria in animal populations. These resistant bacteria can transmit to humans via the food chain or direct contact. Antibiotics are also used in crop production, with streptomycin and oxytetracycline common examples for managing plant diseases.
Environmental contamination is another source of selective pressure. Antibiotics, their residues, and resistant bacteria enter the environment through wastewater from human and animal waste, and agricultural runoff. Rivers, soil, and sewage systems can contain low antibiotic concentrations, sufficient to select for resistant bacteria and facilitate resistance gene spread among different bacterial species.
Impact on Antibiotic Resistance
Continuous selection of resistant bacteria by various antibiotic concentrations has significant implications for public health. This fuels the rise and spread of antibiotic resistance, making infections increasingly difficult to treat. When bacteria become resistant, standard antibiotic therapies may no longer be effective, necessitating more expensive, potentially less effective, or “last-line” alternative drugs.
Consequences include prolonged illnesses, increased healthcare costs, and a higher risk of complications and mortality. Globally, millions of deaths are associated with antibiotic-resistant infections each year. The increasing prevalence of resistance threatens modern medical advancements relying on effective infection control, such as surgery, organ transplants, and cancer therapies.