Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller–Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC(0–24 h)/MIC) to achieve a bactericidal effect was estimated from in vitro time‐kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single‐dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts

EFSA BIOHAZ Panel (EFSA Panel on Biologicial Hazards), 2013. Scientific Opinion on the public health hazards to be covered by inspection of meat (solipeds)

A risk ranking process identified Trichinella spp. as the most relevant biological hazard in the context of meat inspection of domestic solipeds. Without a full and reliable soliped traceability system, it is considered that either testing all slaughtered solipeds for Trichinella spp., or inactivation meat treatments (heat or irradiation) should be used to maintain the current level of safety. With regard to general aspects of current meat inspection practices, the use of manual techniques during current post-mortem soliped meat inspection may increase microbial cross-contamination, and is considered to have a detrimental effect on the microbiological status of soliped carcass meat. Therefore, the use of visual-only inspection is suggested for “non-suspect” solipeds. For chemical hazards, phenylbutazone and cadmium were ranked as being of high potential concern. Monitoring programmes for chemical hazards should be more flexible and based on the risk of occurrence, taking into account Food Chain Information (FCI), covering the specific on-farm environmental conditions and individual animal treatments, and the ranking of chemical substances, which should be regularly updated and include new hazards. Sampling, testing and intervention protocols for chemical hazards should be better integrated and should focus particularly on cadmium, phenylbutazone and priority “essential substances” approved for treatment of equine animals. Implementation and enforcement of a more robust and reliable identification system throughout the European Union is needed to improve traceability of domestic solipeds. Meat inspection is recognised as a valuable tool for surveillance and monitoring of animal health and welfare conditions. If visual only post-mortem inspection is implemented for routine slaughter, a reduction in the detection of strangles and mild cases of rhodococcosis would occur. However, this was considered unlikely to affect the overall surveillance of both diseases. Improvement of FCI and traceability were considered as not having a negative effect on animal health and welfare surveillance

EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), 2013. Scientific Opinion on the public health hazards to be covered by inspection of meat (bovine animals).

A risk ranking process identified Salmonella spp. and pathogenic verocytotoxin-producing Escherichia coli (VTEC) as current high-priority biological hazards for meat inspection of bovine animals. As these hazards are not detected by traditional meat inspection, a meat safety assurance system for the farm-to-chilled carcass continuum using a risk-based approach was proposed. Key elements of the system are risk-categorisation of slaughter animals for high-priority biological hazards based on improved food chain information, as well as risk-categorisation of slaughterhouses according to their capability to control those hazards. Omission of palpation and incision during post-mortem inspection for animals subjected to routine slaughter may decrease spreading and cross-contamination with the high-priority biological hazards. For chemical hazards, dioxins and dioxin-like polychlorinated biphenyls were ranked as being of high potential concern; all other substances were ranked as of medium or lower concern. Monitoring programmes for chemical hazards should be more flexible and based on the risk of occurrence, taking into account the completeness and quality of the food chain information supplied and the ranking of chemical substances, which should be regularly updated to include new hazards. Control programmes across the food chain, national residue control programmes, feed control and monitoring of environmental contaminants should be better integrated. Meat inspection is a valuable tool for surveillance and monitoring of animal health and welfare conditions. Omission of palpation and incision would reduce detection effectiveness for bovine tuberculosis and would have a negative impact on the overall surveillance system especially in officially tuberculosis free countries. The detection effectiveness for bovine cysticercosis, already low with the current meat inspection system, would result in a further decrease, if palpation and incision are removed. Extended use of food chain information could compensate for some, but not all, the information on animal health and welfare lost if only visual post-mortem inspection is applied