Dataset Information

Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens.

ABSTRACT: The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2). Herein, we report the 1-compartment population pharmacokinetics (PK) of colistin in chicken intestine (jejunum and ileum) and combined it with a previously established pharmacodynamic (PD) model of HR in E. coli. We then computed probabilities of target attainment (PTA) with a pharmacodynamic target (AUC_24h/MIC) that achieves 50% of the maximal kill of bacterial populations (considering inoculums of pure S1, S2 or HR mixture of S1 + S2). For an MIC of 1 mg/L, PTA > 95% was achieved with the registered dose (75,000 IU/kg BW/day in drinking water) for the HR mixture of S1 + S2 E. coli, whether they harboured mcr or not. For an MIC of 2 mg/L (ECOFF), we predicted PTA > 90% against the dominant susceptible sub-population (S1) with this clinical dose given (i) over 24 h for mcr-negative isolates or (ii) over 6 h for mcr-positive isolates (pulse dosing). Colistin clinical breakpoint S ≤ 2 mg/L (EUCAST rules) should be confirmed clinically.

SUBMITTER: Mead A

PROVIDER: S-EPMC10406827 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens.

Mead Andrew A Toutain Pierre-Louis PL Richez Pascal P Pelligand Ludovic L

Scientific reports 20230807 1

The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2). Herein, we report the 1-compartment population pharmacokinetics (PK) of colistin in chicken intestine (jejunum and ileum) and combined it with a previously establi ...[more]

PMID: 37550398

Similar Datasets

Project description:Continuous exposure to high ambient temperatures brings about a number of oxidative damages in chickens. Copper (Cu), an active component of a number of antioxidative defence components, should arrest these changes to take place although that may not be possible under the standard dosing regimen followed by the industry. To ascertain the optimum dose response that may be beneficial in sustaining the performance of chickens under heat stress (HS), broiler chickens (n = 400) were exposed to high ambient temperature (between 27.2°C and 35.3°C) during 1-35 d. Copper (Cu) as Cu proteinate (Cu-P) at concentrations of 37.5, 75, 112.5, and 150 mg/kg was supplemented to the diet. The negative control (NC) diet did not contain any supplemental Cu. Increasing dietary Cu improved (P < 0.001) body weight, feed intake, and conversion ratio. Serum concentrations of total cholesterol at 21 d (P = 0.009), HDL cholesterol at 35 d (P = 0.008), LDL cholesterol at 21 d (P = 0.015), and triacylglycerol at both 21 d (P = 0.033) and 35 d (P = 0.001) decreased as Cu in the diet increased. As Cu in the diet increased, hemoglobin increased (P = 0.003) at 21 d, and the heterophil to lymphocyte ratio decreased both at 21 d (P = 0.047) and 35 d (P = 0.001). Superoxide dismutase and glutathione peroxidase activities increased when dietary Cu increased to 150 mg/kg (P < 0.01). Liver Cu at 35 d increased linearly with the dose of Cu in the diet (P = 0.0001). Selected bacteria were enumerated in the digesta to ascertain if Cu super-dosing affected their population in any way in the absence of any enteric challenge. Escherichia coli and total Salmonella numbers decreased (P = 0.0001), and total Lactobacillus increased (P = 0.0001) proportionately with dietary Cu. Interleukin-6 and tumour necrosis factor-α gene expression increased linearly (P = 0.0001) as Cu in the diet increased though the response plateaued at 112.5 mg/kg. It was concluded from the present experiment that during conditions of impending HS, dietary supplementation of 112.5 to 150 mg Cu/kg diet as Cu-P may be a novel strategy to alleviate the negative effects of HS without involving any apparent risk of Cu toxicity.

Project description:Coccidiosis and necrotic enteritis negatively impact poultry production, making challenge model repeatability important for evaluating mitigation strategies. Study objectives were: 1) evaluate Salmonella Typhimurium-Eimeria maxima-Clostridium perfringens necrotic enteritis coinfection model repeatability and 2) investigate E. maxima dose and early S. Typhimurium challenge on immune responses. Three trials using Ross 308 chicks assigned to 12 cages/trial (7 chicks/cage) in wire-floor brooders were completed. Trials 1 and 2 determined E. maxima dose for necrotic enteritis challenge in trial 3. Chicks in trials 1 and 2 were inoculated with 0 (control), 5, 15, or 25,000 sporulated E. maxima M6 oocysts on d 14 and jejunal lesion scores evaluated on d 20. In trial 3, chicks were assigned to control or necrotic enteritis challenge (42 chicks/group). Necrotic enteritis challenge chicks were inoculated with 1 × 105 colony forming units (CFU) S. Typhimurium on d 1, 15,000 E. maxima oocysts on d 14, and 1 × 108 CFU C. perfringens on d 19 and 20 with lesion scoring on d 22. Bird and feeder weights were recorded throughout each trial. Peripheral blood mononuclear cells (PBMC) were isolated from 1 chick/cage at baseline (all trials), 4 chicks/dose (trials 1 and 2) or 8 chicks/challenge (trial 3) 24 h post-inoculation (pi) with E. maxima for immunometabolic assays and immune cell profiling. Data were analyzed by mixed procedure (SAS 9.4) with challenge and timepoint fixed effects (P ≤ 0.05, trends 0.05 ≤ P ≤ 0.01). Inoculating chicks with 15,000 E. maxima oocysts increased d 14 to 20 FCR 79 points (trials 1 and 2; P = 0.009) vs. unchallenged chicks and achieved a target lesion score of 2. While C. perfringens challenge reduced trial 3 performance, average lesion scores were <1. Salmonella inoculation on d 1 tended to increase PBMC ATP production 41.6% 24 hpi with E. maxima vs. chicks challenged with E. maxima only (P = 0.06). These results provide insight for future model optimization and considerations regarding S. Typhimurium's effect on E. maxima immune response timelines.

Dataset Information

Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens.

Publications

Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets