“Acceptable” concentrations of enrofloxacin in food lead to reduced enrofloxacin susceptibility in a mouse model of gastrointestinal <i>Klebsiella pneumoniae</i>

Concentrations of antimicrobials up to 1,000-fold lower than the minimum inhibitory concentration can select for antimicrobial resistance. This generates the hypothesis that the low concentrations of antimicrobials allowed in our food could select for resistance. We assessed if the dose of enrofloxacin allowed in food by the European Medicines Agency (6.2 µg/kg) could decrease susceptibility to enrofloxacin in a strain of Klebsiella pneumoniae colonizing the gastrointestinal tracts of Specific Opportunistic Pathogen-Free Naval Medical Research Institute (NMRI) mice. We found that one-tenth of this dose given daily was able to increase the K. pneumoniae enrofloxacin MIC 8-fold (from 0.047 µg/mL to 0.38 µg/mL). Our findings suggest the need for studies to assess if the same could occur in humans. IMPORTANCE Antimicrobial-resistant infections are responsible for over a million deaths a year. Reducing antimicrobial resistance requires addressing all the sources of unnecessary antimicrobial exposure. Because the antimicrobial concentration in our food frequently approaches or exceeds the maximum allowed limits, it is crucial to ensure that the legal concentrations of antimicrobials in food do not induce antimicrobial resistance. We found that enrofloxacin doses, 10 times lower than those classified as safe, could increase enrofloxacin MICs 8-fold in K. pneumoniae in the gastrointestinal tracts of mice. These findings suggest that we need to consider the induction of antimicrobial resistance when defining safe concentrations of antimicrobials in our food.