The introduction of antibiotics is one of the most important medical interventions with regard to reducing human morbidity and mortality. However, the intensive use of antibiotics (which was estimated in 2002 to be 100,000–200,000 tonnes per annum worldwide and which is, in total, well over 1 million tonnes since the 1940s) has dramatically increased the frequency of resistance among human pathogens and threatens a loss of therapeutic options and a post-antibiotic era in which the medical advances to date are negated. Resistance dramatically reduces the possibility of treating infections effectively and increases the risk of complications and of a fatal outcome.
Most antibiotic resistance mechanisms are associated with a fitness cost that is typically observed as a reduced bacterial growth rate. The magnitude of this cost is the main biological parameter that influences the rate of development of resistance, the stability of the resistance and the rate at which the resistance might decrease if antibiotic use were reduced. These findings suggest that the fitness costs of resistance will allow susceptible bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is reduced. Unfortunately, the available data suggest that the rate of reversibility will be slow at the community level. This paper reviews the factors that influence the fitness costs of antibiotic resistance, the ways by which bacteria can reduce these costs and the possibility of exploiting them. A better understanding of fitness costs and compensatory evolution and their impact on the emergence and spread of resistant bacteria should allow us to make better quantitative predictions about the rate and trajectory of the evolution of resistance towards new and old drugs and offers possibilities to prevent this evolution.
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