Dataset Information

Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model.

ABSTRACT: Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.

SUBMITTER: Temmerman R

PROVIDER: S-EPMC8161238 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Fluoroquinolone agents are considered critical for human medicine by the World Health Organization (WHO). However, they are often used for the treatment of avian colibacillosis in poultry production, creating considerable concern regarding the potential spread of fluoroquinolone resistance genes from commensals to pathogens. Therefore, there is a need to understand the impact of fluoroquinolone application on the reservoir of ARGs in poultry gut and devise means to circumvent potential resistome expansion. Building upon a recent dose optimization effort, we used shotgun metagenomics to investigate the time-course change in the cecal microbiome and resistome of broiler chickens receiving an optimized dosage [12.5 mg/kg body weight (bw)/day], with or without synbiotic supplementation (PoultryStar®, BIOMIN GmbH), and a high dosage of enrofloxacin (50 mg/kg bw/day). Compared to the high dose treatment, the low (optimized) dose of enrofloxacin caused the most significant perturbations in the cecal microbiota and resistome of the broiler chickens, demonstrated by a lower cecal microbiota diversity while substantially increasing the antibiotic resistance genes (ARGs) resistome diversity. Withdrawal of antibiotics resulted in a pronounced reduction in ARG diversity. Chickens receiving the synbiotic treatment had the lowest diversity and number of enriched ARGs, suggesting an alleviating impact on the burden of the gut resistome. Some Proteobacteria were significantly increased in the cecal metagenome of chickens receiving enrofloxacin and showed a positive association with increased ARG burden. Differential abundance (DA) analysis revealed a significant increase in the abundance of ARGs encoding resistance to macrolides-lincosamides-streptogramins (MLS), aminoglycosides, and tetracyclines over the period of enrofloxacin application, with the optimized dosage application resulting in a twofold higher number of affected ARG compared to high dosage application. Our results provide novel insights into the dose-dependent effects of clinically important enrofloxacin application in shaping the broiler gut resistome, which was mitigated by a synbiotic application. The contribution to ameliorating the adverse effects of antimicrobial agents, that is, lowering the spread of antimicrobial resistance genes, on the poultry and potentially other livestock gastrointestinal microbiomes and resistomes merits further study.

Project description:The aim of this work was to study the continuous or intermittent impact of a multienzyme supplement on growth performance, nutrient digestibility, and blood metabolites of broilers, and to evaluate production index of dietary supplementation. A total of 315 unsexed day-old Arbor Acres broiler chicks were randomly distributed to seven treatments groups, keeping initial body weights similar, in 35-floor pens (replicates) of nine chicks per replicate (pen) and five experimental units per treatment. All experimental groups were fed the same basal diet and administered seven multienzyme treatments: the 1st group (control) did not receive any enzyme supplementation; the 2nd, 3rd, and 4th groups were administered multienzymes at 0.5, 1.0, and 1.5 mL/L drinking water, respectively. Each enzyme supplemented-group was divided into two subgroups, with additives being applied either continuously (24 h/day) or intermittently (12 h/day) from 1 to 35 days old. Regardless of administration method, multienzyme supplements at 1.0 mL/L water along with a corn-soybean meal diet increased the body weight gain (BWG) by 7.8% compared to 0.5 mL/L water during days 1-21 of age. In addition, 1.5 mL/L water significantly improved BWG by 5.1% of broilers compared to 0.5 mL/L water during days 1-35 of age. Enzyme supplementation at 1.5 mL/L water significantly enhanced feed conversion ratio (FCR) by 4.3% during days 1-21 of age, and FCR by 5.2% and European production index (EPI) by 10.4% during days 1-35 of age compared to the group on 0.5 mL/L water. For the whole period, there were improvements of beneficial consideration in BWG (4.0%), FCR (4.0%), and European production index (8.2%) due to continuous multienzyme supplementation at 0.5 mL/L water compared to the same dose added intermittently. A similar trend was observed due to intermittent multienzymes at 1 mL/L drinking water that resulted in increased BWG by (6.4%) and improved FCR by (6.7%) and EPI by (12.7%). Intermittent administration significantly increased feed intake of broilers during 22-35 days of age compared to continuous supplementation. Multienzymes at different doses did not significantly affect the digestibility of nutrients, blood serum biochemical constituent, inner body organs, and markers of functions of liver and renal organs. In conclusion, the highest BWG and the best FCR and EPI for the whole period were from broilers given continuous 1 and 1.5 mL/L drinking water or intermittent multienzyme supplementation at 1.5 mL/L drinking water. Furthermore, intermittent supplementation of enzymes at 1 mL/L drinking water and continuous supplementation at 0.5 mL/L drinking water can be investigated in further experiments as a tool to improve broiler growth performance and economic traits and to decrease the cost of enzyme application.

Dataset Information

Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets