Theory 042/Medicine & Health /Pharmacology
Antibiotics Are a Race
Dosing is designed around exposure. The outcome may be a race between killing and regrowth.
Antibiotic efficacy is set by the ratio of kill rate to regrowth rate rather than by the area under the concentration curve, so a drug that kills quickly but clears quickly can outperform one with greater exposure.
01The evidence
Different antibiotic classes show different relationships between exposure and outcome, which is why killing patterns are classified as time- or concentration-dependent.
02The tension
Exposure metrics dominate dosing, and the classification is descriptive rather than mechanistic. It does not predict which regimen will win in a given tissue.
03The mechanism
Bacteria regrow between doses, and regrowth is faster when the drug concentration falls below the mutant selection window. The net effect is the difference between two rates rather than the integral of one.
That makes the ratio the outcome variable, and predicts that dosing frequency should be optimised against regrowth rate rather than against half-life.
04What this is not
Exposure models integrate concentration over time. This treats outcome as a rate difference, which predicts regimen effects at equal exposure.
05Predictions
- P1Outcome should correlate with kill-to-regrowth ratio.
- P2Frequency should matter more than exposure.
- P3Fast-clearing fast killers should outperform slow ones at equal AUC.
06Refutation
Outcome tracking exposure at controlled regrowth would restore the standard metric.
07What it changes
It would change dosing schedules.