Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial lining fluid in naturally occurring bovine respiratory disease in multisource commingled feedlot cattle.

The objectives of this study were to determine (i) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease (BRD) and treated with gamithromycin (Zactran(®) ) at the label dose and (ii) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid (PELF) effect compartment. The study design was a prospective, blinded, randomized clinical trial utilizing three groups of 60 (362-592 lb) steers/bulls randomly allocated within origin to sham injection or gamithromycin mass medication. Cattle were evaluated daily for signs of BRD by a veterinarian blinded to treatment. Animals meeting the BRD case definition were enrolled and allocated to a sample collection scheme consisting of samples for bacterial isolation (bronchoalveolar lavage fluid and nasopharyngeal swabs) and gamithromycin concentration determination (PELF and plasma). Gamithromycin susceptibility of M. haemolytica (n = 287) and P. multocida (n = 257) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16 µg/mL. A two-compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in PELF was developed using rich data sets from published and unpublished studies. The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values. The resulting parameter estimates were used to simulate full time-concentration profiles for each animal in this study. These profiles were analyzed using noncompartmental methods so that PK/PD indices (AUC24 /MIC, AUC∞ /MIC, CMAX /MIC) could be calculated for plasma and PELF (also T>MIC) for each individual. The calculated PK/PD indices were indicative that for both M. haemolytica and P. multocida a higher drug exposure in terms of concentration, and duration of exposure relative to the MIC of the target pathogen, was favorable to a successful case outcome. A significant association was found between treatment success and PELF AUC0-24 /MIC for P. multocida. The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports. Ultimately, the findings from this study indicate that higher PK/PD indices were predictive of positive treatment outcomes.

Protocol for diversion of confirmed positive bulk raw milk tankers to calf ranches - A review of the Pharmacokinetics of tetracyclines and sulfonamides in veal calves.

The tetracyclines (TTC) and sulfonamides are among the most common residues found in bulk raw milk samples. Detection of drug residues in bulk milk (BM) tankers demonstrates that the product is not suitable for human consumption. Discarding BM with residue-contaminated milk is a waste of a valuable commodity, and a repurposing for consumption at calf ranches is a way to recapture some value. However, if calves consuming milk with drug residues are slaughtered for veal, their meat could contain drug residues. The objective of this review is to provide a residue avoidance strategy for TTC and sulfonamide residues in veal. To determine the pharmacokinetic properties of each drug a structured review of the literature was performed and the study inclusion criteria were that the publication used dairy breed calves, with body weight <330 kg or <6 months of age. The most pertinent parameters were determined to be plasma, tissue elimination half-lives, and systemic bioavailability. The results of this review were integrated with milk and tissue testing levels of quantification and tissue tolerances to formulate a recommended withdrawal interval for calves ingesting this milk. The suggested withdrawal interval of 20 days will ensure that no veal calves will test positive for residues from being fed this milk.

A literature review of antimicrobial resistance in Pathogens associated with bovine respiratory disease.

The objective of this paper was to perform a critical review of the literature as it pertains to the current status of antimicrobial resistance in pathogens associated with bovine respiratory disease (BRD) in beef cattle and to provide a concise yet informative narrative on the most relevant publications available. As such, the scientific literature contained in PubMed, AGRICOLA, and CAB were searched in February of 2014 for articles related to susceptibility testing of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni from cases of BRD. Titles and abstracts were read and 105 articles that were relevant to the subject of BRD antibiotic resistance were attained for further review. After the application of exclusion criterion (publications must have originated from North America, be in English, adhere to standards set forth by the Clinical and Laboratory Standards Institute, and be concerning antimicrobial resistance in BRD in beef cattle), 16 articles remained and are the focus of this publication. Due to the disparate data from the few studies that investigate susceptibility testing of BRD pathogens, a quantitative assessment or meta-analysis was not performed on the studies presented in this review. However, considering diagnostic lab data, there appears to be a clear trend of a decrease in susceptibility of the three major BRD pathogens to the antimicrobials used commonly for treatment and control of BRD. Studies performing sensitivity testing on healthy cattle report much lower resistance, but it remains unclear if this is because of a true lack of resistance mechanisms, or if the isolates do contain quiescent genes for resistance that are only phenotypically expressed following the administration of an antimicrobial for either treatment or control of BRD. Future research to address this question of genotype and phenotypic expression before and after antimicrobial administration will further advance our knowledge in this area.