Abstract
Antimicrobial therapy promotes resistance emergence in target infections and in off-target microbiota. Off-target resistance emergence threatens patient health when off-target populations are a source of future infections, as they are for many important drug-resistant pathogens. However, the health risks of antimicrobial exposure in off-target populations remain largely unquantified, making rational antibiotic stewardship challenging. Here, we discuss the contribution of bystander antimicrobial exposure to the resistance crisis, the implications for antimicrobial stewardship, and some novel opportunities to limit resistance evolution while treating target pathogens.
Highlights
Trends in MicrobiologyBystander Selection for Antimicrobial Resistance: Implications for Patient Health. Antimicrobial therapy promotes resistance emergence in target infections and in off-target microbiota
Antimicrobial therapy is a risk factor for subsequent infection with resistant organisms
Concluding Remarks Available data support the precautionary principle for limiting off-target antimicrobial exposure, but quantitative understanding of the risks posed to patient health are lacking
Summary
Bystander Selection for Antimicrobial Resistance: Implications for Patient Health. Antimicrobial therapy promotes resistance emergence in target infections and in off-target microbiota. Enrichment for antimicrobial resistance in a patient’s microbiome could increase the risk that the patient will subsequently have a resistant infection. Antimicrobial Therapy Enriches for Resistance in Off-Target Microbial Populations The human body hosts a diverse microbiota that includes trillions of bacteria [3,20]. By disrupting the intestinal microbiota, antimicrobials promote the invasion and proliferation of resistant bacteria not typically numerous in the gut [30] Important pathogens such as Clostridium difficile and vancomycin-resistant Enterococcus successfully colonize these disrupted environments [30]. The enrichment of resistance genes in off-target populations could put the patient at risk if (i) resistant organisms from off-target populations subsequently cause symptomatic infections, or if (ii) resistance genes in off-target populations are horizontally transferred to pathogens.
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