An experiment was conducted to determine whether a persistent Salmonella newport infection could be established in swine, to determine duration of shedding and distribution of the organism in internal organs, and to determine whether changes occurred in antimicrobial susceptibility or plasmid profile of the organism during the course of long-term infection. Naturally farrowedSalmonella-free pigs (n = 22) were orally exposed to a multiply antimicrobial-resistant zoonotic strain of S newport when they were 7 weeks old. Tonsillar and rectal swab specimens were examined bacteriologically for S newport during the first week after exposure, then weekly for 7 weeks. Fecal samples were likewise examined weekly or every 2 weeks for 28 weeks after exposure. Necropsies of 2 or 3 randomly selected pigs were conducted at 2, 4, 8, 12, 16, 20, 24, and 28 weeks after exposure. A total of 45 specimens/pig representing the following internal organs or tissues were examined bacteriologically for S newport: liver, spleen, kidney, gallbladder, heart, heart blood, lung, stomach, and tonsils; segments of the intestinal tract with corresponding lymph nodes; and lymph nodes from lymphocenters of the head and neck, thoracic cavity, thoracic limbs, abdominal viscera, and abdominal wall. Exposure to S newport induced a mild and transient clinical response. The organism was recovered from 97% of tonsillar swab specimens and 89% of rectal swab specimens collected during 7 weeks after exposure and from 98% of fecal samples collected during 28 weeks after exposure. At necropsy, S newport was recovered most frequently from tonsils (86.4%), followed by segments of the intestinal tract from ileum to rectum (81.8% recovery from cecal contents), and from mandibular (68.2%), jejunal (50%), and ileocolic (45.5%) lymph nodes. Sporadic recoveries of the organism were made from other lymph nodes and from gallbladder, stomach, kidney, spleen, liver, and heart, varying from 2 to 20 weeks after exposure. The cranial portion of jejunum, medial iliac lymph nodes, dorsal superficial cervical lymph node, and heart blood of all pigs were culture-negative. Of 26 representative isolates of S newport recovered from body organs or feces during 28 weeks after exposure, 4 (15.4%) underwent changes in antimicrobial susceptibility pattern. Changes in plasmid profile of the organism were not detected during longterm infection of swine.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after sc and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after sc dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after sc dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 microgram/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for sc dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after sc dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 microgram/ml for IV, sc, and oral administration, respectively. On the basis of maintaining enrofloxacin serum concentrations at 4 times the minimal inhibitory concentration for Pasteurella multocida, oral dosing resulted in the longest maximal time interval between doses of 15.4 hours vs 9.9 hours and 7.4 hours for IV and SC injections, respectively. Because enrofloxacin is widely dispersed in the rabbit's body, it is estimated from the data in this study that in vivo inhibitory concentrations of enrofloxacin for Pasteurella multocida may be maintained at oral dosage regimens equivalent to 5 mg/kg (q 12 h).