Use of antivirulence therapy has assumed that inhibition of bacterial fitness at the site of infection without directly affecting viability will minimize the development of resistance. However, selection for resistant strains is much more likely to occur at sites of colonization or in the environment following excretion of the therapeutic agent. Data are needed regarding whether the drug's target promotes fitness among bacteria in (drug-exposed) niches other than sites of infection. Furthermore, in vivo studies of resistance selection should assess off-target selection for resistance (eg, within the microbiome). Only when such data are available can the risk for development of resistance be gauged appropriately.
Bibliographical noteFunding Information:
This work was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (grants 1 I01 CX000192 01 [to J. R. J.] and I01BX007080 [to T. A. R.]); and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grants R01 AI081719, R21 AI101750, and R41 AI106375 to B. S.).
- antimicrobial resistance
- antimicrobial targets
- resistance selection
- virulence factors