Background: The complex relationship between drug concentrations and bacterial growth rates require not only\nthe minimum inhibitory concentration but also other parameters to capture the dynamic nature of the relationship.\nTo analyse this relationship between tetracycline concentration and growth of Escherichia coli representative of those\nfound in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net\ngrowth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net\ngrowth rate based on Emax model with three parameters: maximum net growth rate (Ã?±max); concentration for a half maximal\nresponse (Emax); and the Hill coefficient (Ã?³).\nResults: The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates\n(P = 0.97). The net growth rate decreased with increasing tetracycline concentrations, and this decline was greater in\nsusceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD600\nvalue of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters\nconfirmed that the Ã?±max between susceptible and resistant strains in the absence of a drug was not different. EC50\nincreased linearly with MIC on a logââ?¬â??log scale, and Ã?³ was different between susceptible and resistant strains.\nConclusions: The in vitro model parameters described the inhibition effect of tetracycline on E. coli when strains\nwere exposed to a wide range of tetracycline concentrations. These parameters, along with in vivo pharmacokinetic\ndata, may be useful in mathematical models to predict in vivo competitive growth of many different strains and for\ndevelopment of optimal dosing regimens for preventing selection of resistance.
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