There are many ways for microorganisms to become resistant, and the following PD data will focus on point mutations that occur at specific frequencies, and the clinical circumstances where the infection site population substantially exceeds the mutational frequency to resistance. It appears that even before a drug is administered, two pathogenic populations coexist, a large population of substantially susceptible organisms with a low MIC and a much smaller group of mutant organisms with an MIC that is higher than that of the parent population due to the mutation. This leads to a differential response to drug administration, with the susceptible population killed substantially, while at the same time, the drug exposure may be permissive for the amplification of the mutant population.