FIG 1 .

Low-level resistance mechanisms (2 to 4× MIC), including low-level intrinsic resistance, might be relevant in the early evolution of resistance, allowing bacteria to persist in the presence of low antibiotic concentrations and providing them the opportunity of evolving toward more effective resistance. Also, when canonical specific mechanisms of resistance are surpassed by high concentrations of antibiotics, the 2- to 4× MIC increases provided by “low-level mechanisms” might be critical to produce therapeutic failure.