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

Abstract

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. Fig 1. ODE schematic. Schematic of the mathematical model for enrofloxacin and ciprofloxacin concentrations throughout the gastrointestinal tract (GIT) of the steer and the effects on the E. coli population. The compartments S, P, and C are antimicrobial concentration in the steer while the compartments E and R describe the bacteria population in the feces.

Antibiotic use practices of veterinarians and para-veterinarians and the implications for antibiotic stewardship in Nigeria

“…Enrofloxacin was amongst the most frequently reported prescribed antibiotics in this study; over a third (38.5%) of the respondents reported prescribing enrofloxacin in animals. Fluoroquinolones are categorised as critically important antimicrobials (CIAs) for human health (Erwin et al 2020 ; WHO 2019 ), and there is concern that the use of enrofloxacin in animals could lead to sharing of genes encoding resistance to fluoroquinolones in people. Veterinarians can play a role in protecting CIAs (Wood 2018 ) such as enrofloxacin by using these as ‘last resort’ antimicrobials.…”

Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves

“…Fluoroquinolone antibiotics such as danofloxacin and enrofloxacin are approved in the US for use in cattle and swine, but their extra-label use has been prohibited by the FDA 11 , 12 . They are effective in clearing susceptible respiratory infections in animals, but they can pass from the general circulation and be accumulated in the intestinal lumen 12 – 14 . The elimination mechanisms of FQs involve renal and hepatic pathways, with the biliary excretion contributing to the accumulation in the intestine 2 , 15 .…”

“…It has recently been shown in pigs that enrofloxacin reached the concentration level that could reduce E. coli population in the intestinal lumen after being administered to two groups of pigs orally and parenterally alike 13 . Altogether, previous studies indicate that the FQ elimination mechanisms can result in the deposition of FQs in the intestinal content to the concentration level that can alter microbial diversity and induce selective pressure, leading to the emergence and spread of antimicrobial resistance (AMR) 12 .…”

Effect of Intramuscularly Administered Oxytetracycline or Enrofloxacin on Vancomycin-Resistant Enterococci, Extended Spectrum Beta-Lactamase- and Carbapenemase-Producing Enterobacteriaceae in Pigs

“…Thus, enrofloxacin can disrupt the gut commensal bacteria, even when treatment is by intramuscular injection [ 90 ]. Enrofloxacin can influence the population dynamics of enteric bacteria and may select for resistance [ 91 ]. Besides, it has been observed that intramuscular enrofloxacin treatment reduces the faecal E. coli wild type population [ 34 , 92 ], and some authors have observed that at the end of enrofloxacin treatment only non-wild type E. coli isolates are found in faeces [ 34 ].…”