Objective-To investigate the epidemiologic and financial impacts of targeted sampling of subpopulations of cows, compared with random sampling of all cows, for classification of dairy herd infection status for paratuberculosis. Animals-All cows from 4 infected herds with a low-to-moderate prevalence of paratuberculosis and from 1 noninfected herd in California. Procedure-The infection status of each cow was classified on the basis of results of an ELISA or combined ELISA and fecal culture results. Thirteen sampling schemes designed to randomly sample cows on the basis of lactation number, stage of lactation, and milk production were evaluated. Sampling without replacement was used to obtain a probability of herd detection of paratuberculosis for each evaluated sampling method and for simulated sample sizes between 30 and 150 cows. Marginal cost-effectiveness analysis was used to determine the cost increase relative to the increase in detection probability. Results-Sampling cows in the third or higher lactation and greater than or equal to 200 days into lactation yielded the highest detection probability in most instances, resulting in a detection probability that was 1.4 to 2.5 times that obtained by sampling 30 cows in the second or higher lactation. Costs of testing via the alternative method with a 95% detection probability were approximately $300 lower in a high-prevalence herd (31 %) and $800 lower in a low-prevalence herd (9%), compared with use of the reference method. Conclusions and Clinical Relevance-Detection of herds with paratuberculosis could be improved, and costs of testing substantially reduced by sampling targeted groups of cows.

Objective-To determine pharmacodynamic cutoffs with pharmacokinetic-pharmacodynamic principles and Monte Carlo simulation (MCS) for use of amoxicillin in pigs to set interpretive criteria for antimicrobial susceptibility testing. Sample-191 plasma disposition curves of amoxicillin obtained from 21 IV, 104 IM, and 66 PO administrations corresponding to 2,098 plasma concentrations. Procedures-A population model of amoxicillin disposition in pigs was developed for PO and IM administration. The MCS method was then used to determine, for various dosage regimens, the proportion of pigs achieving plasma amoxicillin concentrations greater than a selection of possible minimal inhibitory concentrations (MICs) ranging from 0.0625 to 4 mg/L for at least 40% of a 24-hour period. Results-A target attainment rate (TAR) of 90% was never achieved with the breakpoint recommended by the Clinical and Laboratory Standards Institute (0.5 mg/L) when the usual recommended dosage (20 mg/kg/d) was used. Only by dividing the orally administered daily dose into 12-hour administration intervals was a TAR > 90% achieved when the total dose was at least 40 mg/kg for a pathogen having an MIC ≤ 0.0625 mg/L. For the IM route, the TAR of 90% could only be achieved for MICs of 0.0625 and 0.125 mg/L with the use of 15 and 30 mg/kg doses, respectively. Conclusions and Clinical Relevance-Population kinetics and MCS are required to determine robust species-specific interpretive criteria (susceptible, intermediate, and resistant classifications) for antimicrobial susceptibility testing breakpoints (taking into account interanimal variability).