Comparison of the selection of antimicrobial resistance in fecal Escherichia coli during enrofloxacin administration with a local drug delivery system or with intramuscular injections in a swine model

Abstract

This study evaluated, for the first time, the selection of antibiotic resistance in fecal Escherichia coli, a potential reservoir of genes of resistance, during the prolonged exposure to fluoroquinolones after the implantation of a local drug delivery system (LDDS) in a swine model. Fourteen pigs were randomly assigned to group IM (5 mg/kg/day of intramuscular enrofloxacin--EFX) or LD (surgical implantation of EFX-polymethyl-methacrylate peri-femoral implants). Blood samples were collected daily for determination of plasma EFX and ciprofloxacin (CFX) concentrations. Fecal samples were collected daily to determine the E. coli counts and the susceptibility patterns of its isolates as evaluated by antibiotic disk diffusion tests. In both groups, EFX administration significantly reduced the bacterial counts after 2 days. During recolonization, the bacterial counts remained lower than baseline in group IM but not significantly, and almost reached pre-treatment levels in group LD. Susceptibility to EFX, CFX, and nalidixic acid of recolonizing E. coli in LD pigs slightly decreased but remained within the limit of "susceptible" isolates. In contrast, quinolone susceptibility of recolonizing E. coli in IM pigs dropped dramatically (P < 0.0001). In addition, intramuscular exposure to fluoroquinolones significantly decreased the susceptibility of E. coli to ampicillin and trimethoprim-sulfamethoxazole (P < 0.05). In conclusion, the use of a dosing regimen that minimized the intestinal output of fluoroquinolones also minimized the selection of resistance to several classes of antibiotics. This could represent another advantage of LDDS usage compared to long-lasting systemic administration of fluoroquinolones.

Figure 1

Mean plasma enrofloxacin and ciprofloxacin concentrations in IM and LD pigs.

Figure 2

Evolution of the fecal Escherichia coli population size (least-square means, and standard errors). LOD — lower limit of bacterial detection. a,b — least-square means with different superscripts significantly differ

Figure 3

Evolution of Escherichia coli susceptibility to enrofloxacin (least-square means, and standard errors). a,b,c — least-square means with different superscripts or subscripts significantly differ (statistical analysis was performed on log transformed values)

Figure 4

Evolution of Escherichia coli susceptibility to amoxicillin — least-square means and standard errors (statistical analysis was performed on log transformed values).

Figure 5

Evolution of Escherichia coli susceptibility to ampicillin (least-square means, and standard errors). a,b,c — least-square means with different superscripts or subscripts significantly differ (statistical analysis was performed on log transformed values)

Figure 6

Evolution of Escherichia coli susceptibility to trimethoprim-sulfamethoxazole — least-square means, and standard errors. a,b,c,d — least-square means with different superscripts or subscripts significantly differ (statistical analysis was performed on log transformed values)