Antibiotic resistance in the absence of selective pressure

Antibiotic resistance poses a serious threat to modern medical practice making treatment more difficult and is associated with increased mortality among patients infected with resistant organisms. There is clear evidence that acquisition of resistance is associated with a decrease in the fitness of the organisms at least in the short term. Evidence from in vitro experiments indicates that bacteria have the ability to adapt to this deficit and recover fitness on serial passage. More recent results show that identical organisms isolated from patients in outbreaks have an initial deficit but that adaptation occurs in vivo. Strategies directed towards controlling resistance must move beyond wishful thinking that supposes that these organisms will disappear merely with control of prescribing. In some cases, resistance will not disappear because there is no evolutionary disadvantage in being resistant once adaptation has taken place. It is important, therefore, that we direct our efforts towards preventing primary resistance emerging and in limiting the spread of resistant strains. Ultimately, we must look again to new drug discovery to improve our therapeutic armoury.