Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity.

Septic arthritis causes significant morbidity and mortality in veterinary and human clinical practice and is increasingly complicated by multidrug-resistant infections. Intra-articular (IA) antibiotic administration achieves high local drug concentrations but is considered off-label usage, and appropriate doses have not been defined. Using an equine joint model, we investigated the effects of amikacin injected at three different doses (500, 125, and 31.25 mg) on the immune and cartilage responses in tibiotarsal joints. Synovial fluid (SF) was sampled at multiple time points over 24 h, the cell counts determined, and amikacin concentrations measured by liquid chromatography-mass spectrometry. Cytokine concentrations and collagen degradation products in SF were measured by ELISA and multiplex immunoassays. The mean amikacin concentrations in SF were greater than or equal to the minimum inhibitory concentration (MIC) (0.004 mg/ml) for most common equine joint pathogens at all time points tested to 24 h for all three amikacin doses evaluated. The inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) increased significantly in SF in the highest amikacin dose group, despite the fact that increases in SF cell counts were not observed. Similarly, the biomarkers of cartilage type II collagen cleavage (C2C and C12C) were increased in SF following amikacin injection. Mechanistically, we further demonstrated using in vitro studies that chondrocytes and synoviocytes killed by exposure to amikacin underwent apoptotic cell death and were phagocytosed by macrophages in a non-inflammatory process resembling efferocytosis. Neutrophils and T cells were susceptible to amikacin cytotoxicity at clinically relevant doses, which may result in blunting of cellular inflammatory responses in SF and account for the lack of increase in total nucleated cell counts following amikacin injection. In summary, decisions on whether to inject cytotoxic antibiotics such as aminoglycosides intra-articularly and what doses to use should take into account the potential harm that antibiotics may cause and consider lower doses than those previously reported in equine practice.

Reference intervals for coagulation variables in healthy adult domestic goats (Capra aegagrus hircus).

BACKGROUND: Coagulation has not been studied extensively in adult goats, and reference intervals (RIs) for coagulation variables have not yet been established and would be clinically useful. OBJECTIVES: The goal of this study was to establish coagulation variable RIs in adult goats for future coagulation interpretation. METHODS: Blood samples from 40 healthy adult goats were collected, and assays for PT, APTT, D-dimers, antithrombin III, and fibrinogen were performed. Coagulation variable RIs were established using the Reference Value Advisor v2.1. RESULTS: The RIs included: PT, 15.7-19.8 seconds; APTT, 16.2-24.3 seconds; D-dimer, 0-0.68 µg/mL; antithrombin III, 108.6%-156.5%; fibrinogen, 89.5-303.2 mg/dL. CONCLUSIONS: In this brief communication, we report the RIs for coagulation variables in healthy adult goats. Further research will be needed to identify coagulation changes that are associated with specific disease processes of goats.