Pharmacokinetic and Pharmacodynamic Analysis of Ampicillin/Sulbactam and Enrofloxacin in Critically Ill Dogs
Principal Investigator: Julie Menard
Co-PI: Robert Goggs
DESCRIPTION (provided by applicant):
Antimicrobials have revolutionized human and veterinary medicine, but we are on the cusp of a post-antimicrobial era due to bacterial antimicrobial resistance (AMR). Employing pharmacokinetic and pharmacodynamic (PK/PD) approaches to antimicrobial prescribing may help preserve effectiveness. This approach may also reduce inadvertent exposure of pathogens to subtherapeutic concentrations that promote bacterial virulence and select for AMR and avoid subjecting commensal organisms to unnecessary antimicrobials, thereby reducing genotypic variability that promotes AMR.
Critical illness substantially alters PK parameters such as volume of distribution and clearance, reducing the probability of attaining antimicrobial PD targets and increasing patient mortality. For most antimicrobials, PK parameters have been defined in healthy dogs and recommended dosages derived from those studies may not attain the plasma concentrations necessary to treat severe infections in critically ill dogs.
We aim to establish the PK of ampicillin/sulbactam and enrofloxacin in critically ill dogs and to determine whether currently recommended dosages achieve relevant PD targets. We will also evaluate the association between attaining PD targets and clinical outcomes. We will calculate PK parameters from 50 critically ill dogs receiving standardized doses of ampicillin/sulbactam and enrofloxacin. Time above minimum inhibitory concentration (MIC) and area under the curve over MIC will be compared against laboratory determined MIC values for the organisms infecting individual dogs. Where no organisms or resistant organisms are cultured, comparisons with hospital antibiogram derived MIC data for E. coli will be made. We will also perform Monte Carlo simulations to estimate the probability of target attainment at the doses prescribed.