Drug resistance mutations and horizontally acquired
resistance determinants have been studied, mostly in
terms of resistance mechanisms, for several decades
[9,10]. The focus of those studies has been on
mutations and genes that could be associated with
high-level antibiotic resistance. This has provided an
understanding of the mechanisms of resistance in
laboratory isolates and in many cases the results could
also be applied to identify similar alleles or genes in
clinical isolates. However, the real-life problem of resistance
development may be more complex than these
mechanistic studies suggest and may involve more than
simply the presence of one or a few genes or alleles
conferring high-level antibiotic resistance. In natural
and clinical settings bacterial pathogens will be exposed
to a wide range of antibiotic concentrations, often associated
with non-medical use of antibiotics [11,12], and we
argue that the most important antibiotic concentrations
for selecting variants with reduced susceptibility are
those concentrations that are sublethal and allow continued
growth of the pathogen.