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Effect of administration route and dose escalation on plasma and intestinal concentrations of enrofloxacin and ciprofloxacin in broiler chickens.

Devreese M, Antonissen G, De Baere S, De Backer P, Croubels S - BMC Vet. Res. (2014)

Bottom Line: Next to simply reducing antimicrobial consumption, optimizing dosage regimens can be regarded as a suitable strategy to reduce antimicrobial resistance development without jeopardizing therapy efficacy and outcome.The results in plasma and intestinal content demonstrated that biotransformation of enro- to ciprofloxacin in broiler chickens is limited.In general, the intestinal microbiota in cecum and colon is exposed to significant levels of enrofloxacin after conventional treatment (21-130 μg/g).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. mathias.devreese@ugent.be.

ABSTRACT

Background: The (mis)use of fluoroquinolones in the fowl industry has led to an alarming incidence of fluoroquinolone resistance in pathogenic as well as commensal bacteria. Next to simply reducing antimicrobial consumption, optimizing dosage regimens can be regarded as a suitable strategy to reduce antimicrobial resistance development without jeopardizing therapy efficacy and outcome. A first step in order to limit antimicrobial resistance is to assess the exposure of the intestinal microbiota to enrofloxacin after different treatment strategies. Therefore, a study was conducted in broiler chickens to assess the effect of route of administration (oral versus intramuscular) and dose escalation (10 and 50 mg/kg body weight) on plasma and intestinal concentrations of enrofloxacin and its main metabolite ciprofloxacin after treatment with enrofloxacin once daily for five consecutive days. Four different parts of the intestinal tract were sampled: ileum, cecum, colon and cloaca. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify both analytes in plasma and intestinal content. Sample preparation prior to LC-MS/MS analysis consisted of extraction with ethyl acetate. For intestinal content samples PBS buffer was added before extraction. The supernatant was evaporated to dryness and resuspended in water prior to analysis.

Results: The results in plasma and intestinal content demonstrated that biotransformation of enro- to ciprofloxacin in broiler chickens is limited. In general, the intestinal microbiota in cecum and colon is exposed to significant levels of enrofloxacin after conventional treatment (21-130 μg/g). A clear increase of intestinal concentrations was demonstrated after administration of a five-fold higher dose (31-454 μg/g). After intramuscular administration, intestinal concentrations were comparable, except for the higher levels in cloaca due to the complete bioavailability and urinary excretion.

Conclusions: The intestinal microbiota is exposed to high levels of the antimicrobial, after oral as well as parenteral therapy. Furthermore, a dose and time dependent correlation was observed. The impact of the detected intestinal levels on resistance selection in the intestinal microbiota has to be further investigated.

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Related in: MedlinePlus

Enrofloxacin concentrations (average + SD of the three technical replicates) in different parts of the intestinal tract content: ileum (A), cecum (B), colon (C) and cloaca (D), after oral (PO) or intramuscular (IM) administration of 10 mg enrofloxacin/kg BW or 50 mg enrofloxacin/kg BW a day for 5 consecutive days to broiler chickens. Pooled samples (n = 8) were taken at 2, 4 and 100 h after first administration. Values from the different treatment strategies with a different superscript within one time point and within one intestinal segment are statistically different at p < 0.05.
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Fig2: Enrofloxacin concentrations (average + SD of the three technical replicates) in different parts of the intestinal tract content: ileum (A), cecum (B), colon (C) and cloaca (D), after oral (PO) or intramuscular (IM) administration of 10 mg enrofloxacin/kg BW or 50 mg enrofloxacin/kg BW a day for 5 consecutive days to broiler chickens. Pooled samples (n = 8) were taken at 2, 4 and 100 h after first administration. Values from the different treatment strategies with a different superscript within one time point and within one intestinal segment are statistically different at p < 0.05.

Mentions: Intestinal concentrations of enro- and ciprofloxacin after treatment with enrofloxacin are presented in Figures 2 and 3, respectively. The values are presented as mean + SD of the three technical replicates from the pooled samples. Similar to the plasma results, the intestinal concentrations reported here indicate limited biotransformation of enro- to ciprofloxacin. Furthermore, a linear increase in enro- and ciprofloxacin levels after enrofloxacin dose escalation was observed. The route of administration had a limited effect on cecum and colon concentrations, whereas ileal and cloacal levels were respectively lower and higher after intramuscular administration at both doses used.Figure 2


Effect of administration route and dose escalation on plasma and intestinal concentrations of enrofloxacin and ciprofloxacin in broiler chickens.

Devreese M, Antonissen G, De Baere S, De Backer P, Croubels S - BMC Vet. Res. (2014)

Enrofloxacin concentrations (average + SD of the three technical replicates) in different parts of the intestinal tract content: ileum (A), cecum (B), colon (C) and cloaca (D), after oral (PO) or intramuscular (IM) administration of 10 mg enrofloxacin/kg BW or 50 mg enrofloxacin/kg BW a day for 5 consecutive days to broiler chickens. Pooled samples (n = 8) were taken at 2, 4 and 100 h after first administration. Values from the different treatment strategies with a different superscript within one time point and within one intestinal segment are statistically different at p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260181&req=5

Fig2: Enrofloxacin concentrations (average + SD of the three technical replicates) in different parts of the intestinal tract content: ileum (A), cecum (B), colon (C) and cloaca (D), after oral (PO) or intramuscular (IM) administration of 10 mg enrofloxacin/kg BW or 50 mg enrofloxacin/kg BW a day for 5 consecutive days to broiler chickens. Pooled samples (n = 8) were taken at 2, 4 and 100 h after first administration. Values from the different treatment strategies with a different superscript within one time point and within one intestinal segment are statistically different at p < 0.05.
Mentions: Intestinal concentrations of enro- and ciprofloxacin after treatment with enrofloxacin are presented in Figures 2 and 3, respectively. The values are presented as mean + SD of the three technical replicates from the pooled samples. Similar to the plasma results, the intestinal concentrations reported here indicate limited biotransformation of enro- to ciprofloxacin. Furthermore, a linear increase in enro- and ciprofloxacin levels after enrofloxacin dose escalation was observed. The route of administration had a limited effect on cecum and colon concentrations, whereas ileal and cloacal levels were respectively lower and higher after intramuscular administration at both doses used.Figure 2

Bottom Line: Next to simply reducing antimicrobial consumption, optimizing dosage regimens can be regarded as a suitable strategy to reduce antimicrobial resistance development without jeopardizing therapy efficacy and outcome.The results in plasma and intestinal content demonstrated that biotransformation of enro- to ciprofloxacin in broiler chickens is limited.In general, the intestinal microbiota in cecum and colon is exposed to significant levels of enrofloxacin after conventional treatment (21-130 μg/g).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. mathias.devreese@ugent.be.

ABSTRACT

Background: The (mis)use of fluoroquinolones in the fowl industry has led to an alarming incidence of fluoroquinolone resistance in pathogenic as well as commensal bacteria. Next to simply reducing antimicrobial consumption, optimizing dosage regimens can be regarded as a suitable strategy to reduce antimicrobial resistance development without jeopardizing therapy efficacy and outcome. A first step in order to limit antimicrobial resistance is to assess the exposure of the intestinal microbiota to enrofloxacin after different treatment strategies. Therefore, a study was conducted in broiler chickens to assess the effect of route of administration (oral versus intramuscular) and dose escalation (10 and 50 mg/kg body weight) on plasma and intestinal concentrations of enrofloxacin and its main metabolite ciprofloxacin after treatment with enrofloxacin once daily for five consecutive days. Four different parts of the intestinal tract were sampled: ileum, cecum, colon and cloaca. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify both analytes in plasma and intestinal content. Sample preparation prior to LC-MS/MS analysis consisted of extraction with ethyl acetate. For intestinal content samples PBS buffer was added before extraction. The supernatant was evaporated to dryness and resuspended in water prior to analysis.

Results: The results in plasma and intestinal content demonstrated that biotransformation of enro- to ciprofloxacin in broiler chickens is limited. In general, the intestinal microbiota in cecum and colon is exposed to significant levels of enrofloxacin after conventional treatment (21-130 μg/g). A clear increase of intestinal concentrations was demonstrated after administration of a five-fold higher dose (31-454 μg/g). After intramuscular administration, intestinal concentrations were comparable, except for the higher levels in cloaca due to the complete bioavailability and urinary excretion.

Conclusions: The intestinal microbiota is exposed to high levels of the antimicrobial, after oral as well as parenteral therapy. Furthermore, a dose and time dependent correlation was observed. The impact of the detected intestinal levels on resistance selection in the intestinal microbiota has to be further investigated.

Show MeSH
Related in: MedlinePlus