Creeping baselines and adaptive resistance to antibiotics.

The introduction of antimicrobial drugs in medicine gave hope for a future in which all infectious diseases could be controlled. Decades later it appears certain this will not be the case, because antibiotic resistance is growing relentlessly. Bacteria possess an extraordinary ability to adapt to environmental challenges like antimicrobials by both genetic and phenotypic means, which contributes to their evolutionary success. It is becoming increasingly appreciated that adaptation is a major mechanism behind the acquisition and evolution of antibiotic resistance. Adaptive resistance is a specific class of non-mutational resistance that is characterized by its transient nature. It occurs in response to certain environmental conditions or due to epigenetic phenomena like persistence. We propose that this type of resistance could be the key to understanding the failure of some antibiotic therapy programs, although adaptive resistance mechanisms are still somewhat unexplored. Similarly, hard wiring of some of the changes involved in adaptive resistance might explain the phenomenon of "baseline creep" whereby the average minimal inhibitory concentration (MIC) of a given medically important bacterial species increases steadily but inexorably over time, making the likelihood of breakthrough resistance greater. This review summarizes the available information on adaptive resistance.