Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations

Standard infectious disease practice calls for aggressive drug treatment that rapidly eliminates the pathogen population before resistance can emerge. When resistance is absent, this elimination strategy can lead to complete cure. However, when resistance is already present, removing drug-sensitive cells as quickly as possible removes competitive barriers that may slow the growth of resistant cells. In contrast to the elimination strategy, the containment strategy aims to maintain the maximum tolerable number of pathogens, exploiting competitive suppression to achieve chronic control. Here we combine in vitro experiments in computer-controlled bioreactors with mathematical modeling to investigate whether containment strategies can delay failure of antibiotic treatment regimens. To do so, we measured the \"escape time\" required for drug-resistant E. coli populations to eclipse a threshold density maintained by adaptive antibiotic dosing. Populations containing only resistant cells rapidl...