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The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean ± SE) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 μg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations.

Mainstream human rights activists typically attribute the signature successes of their movement (e.g. antislavery, Gandhi, Martin Luther King) to their uncompromisingly principled stance on behalf of the weak and the exploited. Naming and shaming and ending impunity loom large in their lore. This attitude works well to recruit idealistic activists, but their moralism, legalism, and secular universalism miss the central role of the self-interest of the majority in powering the progress of human rights. A core of idealists has defined aspirational goals, but progress has depended on support from majority mass movements and reform parties that gained power through expedient compromise. The human rights enterprise is now facing fierce pushback from illiberal strongmen and populists who counter-shame the liberal order as decadent, degenerate, and threatening to deeply rooted values. Too often, contemporary rights rhetoric plays into the hands of these illiberal critics. Human Rights for Pragmatists explains how rights-based societies can recover a more accurate narrative of their past pragmatic successes, repair their tactical flaws, and withstand illiberal challenges. [ABSTRACT FROM AUTHOR]