Article Figures & Data
Figures
- FIG. 1.
Effects of various concentrations of enrofloxacin on survival of Salmonella serovar Typhimurium strains in chicken sera at 41°C. Counts are means of two experiments, and error bars are standard errors of the means. The dotted line is the limit of detection. A. Parent strain A (fully sensitive; ciprofloxacin MIC, 0.03 μg/ml). B. MAR strain B (isogenic mutant of strain A; ciprofloxacin MIC, 0.6 μg/ml). C. VLA 512/98 (strain C, nonisogenic gyrA mutant, cyclohexane sensitive; ciprofloxacin MIC, 0.25 μg/ml). D. VLA 2590/99 (strain D, nonisogenic gyrA mutant, cyclohexane tolerant; ciprofloxacin MIC, 1 μg/ml). Symbols: filled diamonds, control; open squares, 0.5 μg/ml enrofloxacin; open triangles, 1.0 μg/ml enrofloxacin; crosses, 2.0 μg/ml enrofloxacin; open diamonds, 4.0 μg/ml enrofloxacin; open circles, 8.0 μg/ml enrofloxacin.
- FIG. 2.
Graphs showing mean (n = 3) fluoroquinolone (enrofloxacin and ciprofloxacin) concentrations in chicken sera and tissues at 0, 2, 4, 6, 8, 10, and 24 h after dosing with Baytril 10% oral solution. (As enrofloxacin can be metabolized to ciprofloxacin in vivo, a percentage of the antibiotic detected was ciprofloxacin.) (A) Cecal contents; (B) liver; (C) lung; (D) sera. Values are for total antibiotic. Symbols: dashed lines and squares, continuous dosing; solid lines and circles, pulsed dosing; open squares or circles, recommended dose; filled squares or circles, 2.5× standard dose.
Tables
- TABLE 1.
Efficacy of recommended and modified enrofloxacin treatments against experimental Salmonella serovar Typhimurium infections in chickens and selection of reduced fluoroquinolone susceptibilitya
Dose method Expt no. Dose level No. of chicks/group No. of days of dose Mean log CFU/g cecal contentsb (± SEM) P value, treatment vs controlc No. of colonies replica plated during/after treatmentd % Colonies with reduced susceptibilitye during/after treatment Water, continuous I Control 10 NA 6.8 (0.76) NA 400/187 0/0 50 ppmf 30 5 0.2 (1.14) <0.001 1,328/752 0.4/43 125 ppm 30 2 0.4 (0.86) <0.001 1,824/3,859 0/96 250 ppm 25 1 4.3 (0.77) 0.213 969/3,089 0/14 IV Control 20 NA 6.0 (0.67) NA ND/672 ND/0 50 ppmf 20 5 <1.0 (0) <0.001 ND/825 ND/0 125 ppm 20 2 3.5 (0.94) 0.006 ND/632 ND/0 Water, pulsed IIIg Control 13 NA 5.1 (0.25) NA ND/206 ND/0 10 mg/kg 15 5 0.6 (0.87) <0.001 ND/33 ND/0 25 mg/kg 15 2 <1.0 (0) <0.001 ND/293 ND/0 50 mg/kg 15 1 1.9 (0.25) <0.001 ND/335 ND/0 IV Control 20 NA 6.0 (0.67) NA ND/672 ND/0 50 ppm 20 5 4.9 (2.84) 0.493 ND/974 ND/42 125 ppm 20 2 3.9 (0.24) 0.005 ND/1,255 ND/23 Gavage II Control 24 NA 8.2 (0.69) NA 394/1,242 0/0 10 mg/kg 51 5 2.7 (1.25) <0.001 2,920/2,474 42/100 25 mg/kg 41 2 2.0 (1.40) <0.001 1,206/2,010 0/0 50 mg/kg 34 1 5.2 (0.69) 0.051 1,455/1,999 0/14 IIIg Control 13 NA 5.1 (0.25) NA ND/206 ND/0 10 mg/kg 15 5 <1.0 (0) <0.001 ND/62 ND/0 25 mg/kg 15 2 0.4 (1.47) <0.001 ND/206 ND/0 50 mg/kg 15 1 2.4 (0.25) <0.001 ND/128 ND/0 ↵ a NA, not applicable; ND, not determined. Values in boldface indicate counts reduced by at least 4 logs.
↵ b Counts were made 1 day after the last antibiotic dose to reduce the effect of any recolonization following the end of therapy.
↵ c P value denotes significance of antibiotic therapy in reducing Salmonella counts compared to control.
↵ d Colonies were replica plated from many representative plates (and hence different birds) from all time points for up to 4 weeks post-antibiotic treatment.
↵ e Reduced susceptibility, e.g., able to grow in the presence of 4× the ciprofloxacin MIC of the original strains.
↵ f The current and recent data sheet-recommended treatment is water adjusted to give 10 mg/kg of bird or water at 50 ppm for 5 days supplied continuously in the water.
↵ g In experiment III birds received a lower challenge of Salmonella, which resulted in a lower level of colonization.
- TABLE 2.
Mean fluoroquinolone (ciprofloxacin and enrofloxacin) concentrations in sera and tissues of chickens following different treatment regimens of Bayril 10% oral solution
Dose method Tissue Dose Mean (SEM) antibiotic concna (μg/ml) at h after start of antibiotic treatment (n = 4 for gavage; n = 3 for other treatments) 2 4 6 8 10 24 Gavageb Cecalc 1× 20.10 (5.95) ND 78.01 (9.44) ND ND 10.79 (4.07) 2.5× 46.46 (6.59) ND 115.86 (35.33) ND ND 50.53 (5.34) Liver 1× 10.61 (0.50) ND 5.46 (0.76) ND ND 1.86 (0.57) 2.5× 20.74 (0.86) ND 15.79 (1.24) ND ND 2.6 (0.15) Sera 1× 1.81 (0.14) ND 0.72 (0.14) ND ND 0.08 (0.01) 2.5× 3.83 (0.35) ND 2.16 (0.19) ND ND 0.18 (0.01) Water, continuous Cecal 1× 3.79 (0.42) 9.88 (2.25) 20.64 (1.63) 24.73 (1.82) 20.28 (0.86) 23.59 (4.01) 2.5× 6.61 (1.00) 30.51 (2.40) 41.54 (0.75) 52.69 (8.05) 63.23 (5.75) 68.02 (0.92) Liver 1× 2.85 (0.74) 3.81 (1.60) 4.97 (0.15) 5.15 (0.21) 6.23 (0.81) 4.94 (0.63) 2.5× 5.86 (3.05) 6.53 (3.32) 9.17 (1.13) 12.67 (1.88) 10.54 (0.81) 11.46 (1.40) Lung 1x 0.85 (0.20) 1.14 (0.52) 1.38 (0.06) 1.80 (0.44) 1.38 (0.08) 1.00 (0.14) 2.5× 1.53 (0.73) 3.06 (0.73) 2.97 (0.27) 3.93 (0.06) 3.39 (0.25) 2.35 (0.39) Sera 1× 0.46 (0.14) 0.53 (0.09) 0.59 (0.006) 0.50 (0.03) 0.73 (0.03) 0.51 (0.15) 2.5× 0.58 (0.29) 0.91 (0.19) 1.42 (0.07) 1.54 (0.19) 1.54 (0.11) 1.11 (0.12) Water, pulsed Cecal 1× 9.48 (0.60) 32.28 (2.47) 43.13 (7.20) 53.19 (8.86) 35.15 (5.77) 12.00 (0.33) 2.5× 17.35 (0.73) 55.52 (10.82) 58.72 (14.27) 115.63 (17.31) 85.70 (38.25) 18.26 (6.65) Liver 1× 3.98 (0.31) 9.13 (0.56) 11.94 (0.96) 9.49 (1.32) 4.93 (0.60) 1.29 (0.25) 2.5× 9.82 (0.73) 11.06 (5.57) 17.87 (2.61) 13.86 (0.35) 8.77 (1.80) 2.61 (0.14) Lung 1× 1.28 (0.23) 2.36 (0.16) 2.79 (0.31) 2.23 (0.35) 1.20 (0.19) 0.20 (0.02) 2.5× 4.91 (8.15) 8.15 (0.92) 6.81 (1.93) 4.41 (0.64) 2.07 (0.25) 0.45 (0.06) Sera 1× 0.45 (0.05) 0.77 (0.007) 1.17 (0.11) 0.97 (0.12) 0.30 (0.13) 0.07 (0.02) 2.5× 1.17 (0.05) 2.74 (0.17) 2.57 (0.50) 1.76 (0.23) 1.84 (0.89) 0.01 (0.001) ↵ a As enrofloxacin can be metabolized to ciprofloxacin in vivo, various percentages (the highest percentage being seen in the liver) of the antibiotic detected were ciprofloxacin, but values are for total antibiotic. ND, not determined.
↵ b Antibiotic concentrations are recorded on day 1 of treatment with the exception of the 24-h results for birds dosed by gavage, which are 24 h after the last dose of the 5-day (recommended dose) or 2-day (2.5× recommended dose) treatment regimens.
↵ c Cecal refers to cecal luminal contents.
- TABLE 3.
Pharmacokinetic parameters (based on mean values) for enrofloxacin in sera of poultrya
Variable and unitd Value for treatment regimenb WC WP R 2.5× R 2.5× C max (μg/ml) 0.73 1.54 1.17 2.74 T max (h) 10 8 6 4 AUC0-24 (μg · h/ml) 13.6 29 9.6 31.3 MRT (h) 42.4 46.2 9.2 7.5 t 1/2 (h) 27.05 29.63 6.47 1.99 C max/MIC (ratio of Cmax/ MIC for strainsc) A 24.3 51.3 39.0 91.3 B 12.1 25.7 19.5 45.7 C 1.46 3.08 2.3 5.5 D 0.73 1.5 1.17 2.7 AUIC (ratio of AUC/ MIC for strainsc) A 453.3 966.7 320 1,043.3 B 226.7 483.3 160 512.7 C 27.2 58 19.2 62.6 D 13.6 29 9.6 31.3 ↵ a Birds were killed to obtain sera and tissues, and so values are calculated from mean serum concentrations from three different birds at each time point.
↵ b WC, continuous water treatment; WP, pulsed water treatment; R, recommended treatment of water at 50 ppm (continuous) or water adjusted to give 10 mg/kg of bird (pulsed); 2.5×, 2.5× recommended treatment.
↵ c Strain A, B, C, or D.
↵ d C max, maximum concentration in serum after administration; Tmax, time needed to reach Cmax; AUC0-24, area under the concentration-time curve for 0 to 24 h; MRT, mean residence time (time for 63.2% of administered dose to be eliminated); t1/2, time for concentration to diminish by one-half.
