The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Erwin, Samantha; Foster, Derek M.; Jacob, Megan E.; Papich, Mark G.; Lanzas, Cristina

doi:10.1371/journal.pone.0228138

The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Journal Article · Thu Jan 30 23:00:00 EST 2020 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0228138· OSTI ID:1606808

^[1]; ^[2]; Jacob, Megan E. ^[2]; Papich, Mark G. ^[2]; Lanzas, Cristina ^[2]

North Carolina State Univ., Raleigh, NC (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
North Carolina State Univ., Raleigh, NC (United States)

Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); National Science Foundation (NSF); USDA; Bayer Animal Health

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1606808

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 1 Vol. 15; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

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