Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose

doi:10.1128/aac.03919-14

Cited by 21 publications

(16 citation statements)

References 34 publications

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“…Understanding how antimicrobial drug regimens influence enteric bacteria in food animals is a relevant public health concern as food animals are a reservoir for zoonotic enteric bacteria, including resistant bacteria. In recent years, mathematical models of different complexities have been developed to investigate the underlying relationships between antimicrobial use and gut bacteria dynamics [28][29][30][31]. Most studies combined data from the literature to parameterize the models.…”

Section: Discussionmentioning

confidence: 99%

The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Erwin¹,

Foster²,

Jacob³

et al. 2020

PLoS ONE

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Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment. Fig 1. ODE schematic. Schematic of the mathematical model for enrofloxacin and ciprofloxacin concentrations throughout the gastrointestinal tract (GIT) of the steer and the effects on the E. coli population. The compartments S, P, and C are antimicrobial concentration in the steer while the compartments E and R describe the bacteria population in the feces.

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Section: Discussionmentioning

confidence: 99%

The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Erwin¹,

Foster²,

Jacob³

et al. 2020

PLoS ONE

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“…Several studies modeling the development of tetracycline resistance in pigs following treatment under different scenarios have recently been published (22,(40)(41)(42). Such models have been fed with data on the growth responses of E. coli to different concentrations of tetracycline.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

Græsbøll

Damborg

Mellerup³

et al. 2017

Appl Environ Microbiol

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This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracyclineresistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracyclineresistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin-and sulfonamide-resistant strains but not to selection for cefotaximeresistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested.IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or smallgroup treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an

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“…The obtained results showed no difference in MIC values of the bacterial strain between the activity of TC-hcl and TC-nm. This indicated that the nanoemulsion formulation reported to be efferent against manybacterial strains [12][13][14][15][16]. The active tetracycline in oil phase of oil-in-water nano-emulsion is protected from hydrolysis and oxidation [64,65].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…Tetracycline hydrochloride-loaded particles was reported to be efferent against H. pylori [12] , P. aeruginosa [13], E. coli strains in pigs [14], Salmonella spp. E. coli 0157:H7 (VT-), P.aeruginosa, Staph.aureus and L.monocytogenes [15].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological studies on tetracycline and tetracycline nanoemulsion formulas. Mohamed S. Saber1, Aziza M. Amer2, Shymaa A. ElBadawy2, Mohamed M. Amer3, 1. PhD student in Pharmacol. , Vet. Service Division, Ministry of Defense, Egypt.. 2. 2. Dept. of Pharmacol., Facult. Vet. Med., Cairo University, Giza, Egypt. 3. 3. Dept. of Poult. Dis., Facult. Vet. Med., Cairo University, P.O. 12211, Giza, Egypt.

et al. 2019

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T HE study was done to compare the pharmacokinetic and pharmacodynamics of 50 mg/ kg b.wttetracycline hydrochloride (TC-hcl) and tetracycline nanoemulsion (TC-nm) formulasin rabbits and detection of their effect on stander and field bacterial strains. After oral TC concentration in plasma started to be detected at 0.25 h, reach the maximum at (0.5 h Tc-hcl) and 1 h.(TC-nm) and decline at 12 hours. Following a single i.v administration a volume of distribution V2 (0.292±0.111 L/kg) in TC-nm than for TC-hcl (0.216 ± 0.183L/kg) and was slowly cleared (0.393±0.183 L.h/kg) in Tc-nm than in TC-hcl (0.415±0.311 L.h/kg). After oral administration a rapidly absorbed with significant slowly absorption half-life t1/2 alpha (0.550±0.090 h and 0.176±0.058 h.) and elimination half-life t1/2 beta (4.215±1.661 h. and 1.58±1.447 h.) with higher calculated Cmax of (4.215±1.661 μg/ml and 1.58±1.447 μg/ml) achieved at prolonged calculated tmax (0.759±0.149h. and 0.356±0.305 h.) in TC-nm than in TC-hcl, respectively. The value of TC-hcl and TC-nm MIC was the same for Staph. Aureus 6538, Staph. Epidermidis12228 ,E.coli 8739 were 0.14, 0.8 and 0.12 µg , respectively, and interpreted as sensitive. Field sensitive Corynebacterium, E.coli , S. typhimurium, S. enteriditisand Staph.leutus isolates MIC value was 1.4, 8, 2, 1.6 and 2 µg for , respectively. Tetracycline resistant2Staph.scuiri (18 and 16µg) and 2 Staph. xylosis (18 and 6µg).

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Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

Cited by 21 publications

References 34 publications

The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

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