Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

Amais Ahmad; Camilla Zachariasen; Lasse Engbo Christiansen; Kaare Græsbøll; Nils Toft; Louise Matthews; Peter Panduro Damborg; Yvonne Agersø; John Elmerdahl Olsen; Søren Saxmose Nielsen

doi:10.1186/s13028-015-0169-0

Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

Amais Ahmad, Camilla Zachariasen, Lasse Engbo Christiansen, Kaare Græsbøll, Nils Toft, Louise Matthews, Peter Panduro Damborg, Yvonne Agersø, John Elmerdahl Olsen, Søren Saxmose Nielsen

Sektion, Food Safety and Zoonoses

11 Citationer (Scopus)

357 Downloads (Pure)

Abstract

Background: The complex relationship between drug concentrations and bacterial growth rates require not only the minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship. To analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E_max model with three parameters: maximum net growth rate (α_max); concentration for a half-maximal response (E_max); and the Hill coefficient (γ). Results: The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD₆₀₀ value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the (α_max between susceptible and resistant strains in the absence of a drug was not different. EC₅₀ increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. Conclusions: The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains were exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic data, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for development of optimal dosing regimens for preventing selection of resistance.

Originalsprog	Engelsk
Artikelnummer	79
Tidsskrift	Acta Veterinaria Scandinavica (Online)
Vol/bind	57
Antal sider	8
ISSN	0044-605X
DOI	https://doi.org/10.1186/s13028-015-0169-0
Status	Udgivet - 24 nov. 2015

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10.1186/s13028-015-0169-0Licens: CC BY

Ahmad_Zachariasen_Christiansen_Graesboll_Toft_Matthews_Damborg_Agerso_Olsen_Nielsen_2015Forlagets udgivne version, 1,98 MB
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Ahmad, A., Zachariasen, C., Christiansen, L. E., Græsbøll, K., Toft, N., Matthews, L., Damborg, P. P., Agersø, Y., Olsen, J. E., & Nielsen, S. S. (2015). Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli. Acta Veterinaria Scandinavica (Online), 57, [79]. https://doi.org/10.1186/s13028-015-0169-0

Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli. / Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo et al.

I: Acta Veterinaria Scandinavica (Online), Bind 57, 79, 24.11.2015.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Ahmad, A, Zachariasen, C, Christiansen, LE, Græsbøll, K, Toft, N, Matthews, L, Damborg, PP, Agersø, Y, Olsen, JE & Nielsen, SS 2015, 'Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli', Acta Veterinaria Scandinavica (Online), bind 57, 79. https://doi.org/10.1186/s13028-015-0169-0

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title = "Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli",

abstract = "Background: The complex relationship between drug concentrations and bacterial growth rates require not only the minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship. To analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on Emax model with three parameters: maximum net growth rate (αmax); concentration for a half-maximal response (Emax); and the Hill coefficient (γ). Results: The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD600 value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the (αmax between susceptible and resistant strains in the absence of a drug was not different. EC50 increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. Conclusions: The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains were exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic data, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for development of optimal dosing regimens for preventing selection of resistance.",

author = "Amais Ahmad and Camilla Zachariasen and Christiansen, {Lasse Engbo} and Kaare Gr{\ae}sb{\o}ll and Nils Toft and Louise Matthews and Damborg, {Peter Panduro} and Yvonne Agers{\o} and Olsen, {John Elmerdahl} and Nielsen, {S{\o}ren Saxmose}",

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doi = "10.1186/s13028-015-0169-0",

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T1 - Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

AU - Ahmad, Amais

AU - Zachariasen, Camilla

AU - Christiansen, Lasse Engbo

AU - Græsbøll, Kaare

AU - Toft, Nils

AU - Matthews, Louise

AU - Damborg, Peter Panduro

AU - Agersø, Yvonne

AU - Olsen, John Elmerdahl

AU - Nielsen, Søren Saxmose

PY - 2015/11/24

Y1 - 2015/11/24

N2 - Background: The complex relationship between drug concentrations and bacterial growth rates require not only the minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship. To analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on Emax model with three parameters: maximum net growth rate (αmax); concentration for a half-maximal response (Emax); and the Hill coefficient (γ). Results: The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD600 value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the (αmax between susceptible and resistant strains in the absence of a drug was not different. EC50 increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. Conclusions: The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains were exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic data, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for development of optimal dosing regimens for preventing selection of resistance.

AB - Background: The complex relationship between drug concentrations and bacterial growth rates require not only the minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship. To analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on Emax model with three parameters: maximum net growth rate (αmax); concentration for a half-maximal response (Emax); and the Hill coefficient (γ). Results: The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD600 value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the (αmax between susceptible and resistant strains in the absence of a drug was not different. EC50 increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. Conclusions: The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains were exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic data, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for development of optimal dosing regimens for preventing selection of resistance.

U2 - 10.1186/s13028-015-0169-0

DO - 10.1186/s13028-015-0169-0

M3 - Journal article

C2 - 26603151

SN - 0044-605X

VL - 57

JO - Acta Veterinaria Scandinavica

JF - Acta Veterinaria Scandinavica

M1 - 79

ER -

Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

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