Pharmacokinetics and Effectiveness of Precise Voluntary Consumption Compared to Subcutaneous Administration of Cephalosporins in Rats following Orthopedic Surgery

The administration of antibiotics is a critical variable when developing animal models of infection. Handling and needle use, however, can cause distress in the animals, leading not only to irritability of the animal but potentially skewed inflammatory data in studies that closely measure this response. Cefadroxil, a cephalosporin with excellent intestinal absorption, can be administered enterally. Oral gavage and drinking water dosing, 2 common methods of oral administration, each have their own disadvantages, including distress as a result of handling and potential death from accidental drug administration into the lungs; and incomplete consumption, respectively. Here, we developed and evaluated a method for precise voluntary oral consumption of cefadroxil for use in a rodent model of musculoskeletal infection. Sprague-–Dawley rats were trained to voluntarily consume a wafer or puree containing 1 of 2 doses of cefadroxil. Blood plasma was collected to measure systemic concentrations of antibiotics 30, 60, and 120 min following consumption. Finally, the voluntary consumption method was used in a rat model of musculoskeletal infection to evaluate efficacy. Following a 5-d training regimen, the number of animals that consistently ate the drug increased from 2/10 to 10/10 and the time to consume decreased from 16 min to 6 min. The highest cefadroxil dose, 23.2 mg/kg, reached a peak plasma concentration of 4.8 μg/mL, 1 h after consumption when the puree was used compared with 2.9 μg/mL, 2 h after wafer consumption. When used in a rat model of musculoskeletal infection, the rats continued to voluntarily consume the drug, and consumption of cefadroxil by puree reduced the bacteria bioburden in the bone tissue compared with the nontreated control. Our results show that precise voluntary consumption is a viable method to administer drugs to rats.