Objective-To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. Animals-10 healthy blue and gold macaws. Procedures-In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. Results-After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microgram.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microgram/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microgram.h/mL, and the harmonic mean terminal half-life was 4.3 hours. Conclusions and Clinical Relevance-Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.

Objective-To evaluate various sampling strategies for potential use in measuring prevalence of antimicrobial susceptibility in cattle. Sample Population-500 isolates of non-type-specific Escherichia coli (NTSEC) isolated from the feces of 50 cows from 2 dairy farms (25 cows/farm and 10 isolates/cow). Procedures-Diameters of inhibition zones for 12 antimicrobials were analyzed to estimate variation among isolates, cows, and farms and then used to determine sampling distributions for a stochastic simulation model to evaluate 4 sampling strategies. These theoretic sampling strategies used a total of 100 isolates in 4 allocations (1 isolate from 100 cows, 2 isolates from 50 cows, 3 isolates from 33 cows, or 4 isolates from 25 cows). Results-Analysis of variance composition revealed that 74.2% of variation was attributable to isolates, 18.5% to cows, and 7.3% to farms. Analysis of results of simulations suggested that when most of the variance was attributable to differences among isolates within a cow, culturing 1 isolate from each of 100 cows underestimated overall prevalence, compared with results for culturing more isolates per cow from fewer cows. When variance was not primarily attributable to differences among isolates, all 4 sampling strategies yielded similar results. Conclusions and Clinical Relevance-It is not always possible to predict the hierarchical level at which clustering will have its greatest impact on observed susceptibility distributions. Results suggested that sampling strategies that use testing of 3 or 4 isolates/cow from a representative sample of all animals better characterize herd prevalence of antimicrobial resistance when impacted by clustering.

Objective - To evaluate the effectiveness of various sampling techniques for determining antimicrobial resistance patterns in Escherichia coli isolated from feces of feedlot cattle. Sample Population - Fecal samples obtained from 328 beef steers and 6 feedlot pens in which the cattle resided. Procedure - Single fecal samples were collected from the rectum of each steer and from floors of pens in which the cattle resided. Fecal material from each single sample was combined into pools containing 5 and 10 samples. Five isolates of Escherichia coli from each single sample and each pooled sample were tested for susceptibility to 17 antimicrobials. Results - Patterns of antimicrobial resistance for fecal samples obtained from the rectum of cattle did not differ from fecal samples obtained from pen floors. Resistance patterns from pooled samples differed from patterns observed for single fecal samples. Little pen-to-pen variation in resistance prevalence was observed. Clustering of resistance phenotypes within samples was detected. Conclusions and Clinical Relevance - Studies of antimicrobial resistance in feedlot cattle can rely on fecal samples obtained from pen floors, thus avoiding the cost and effort of obtaining fecal samples from the rectum of cattle. Pooled fecal samples yielded resistance patterns that were consistent with those of single fecal samples when the prevalence of resistance to an antimicrobial was > 2%. Pooling may be a practical alternative when investigating patterns of resistance that are not rare. Apparent clustering of resistance phenotypes within samples argues for examining fewer isolates per fecal sample and more fecal samples per pen.

The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

Objective-To determine the susceptibility of strains of Pasteurella multocida subsp multocida isolated from lung specimens of pigs with pneumonia to 20 antimicrobials and to evaluate the emergence of resistance to those antimicrobials in Spain during the past 2 decades. Sample Population-63 isolates recovered from 1987 to 1988 and 132 isolates recovered from 2003 to 2004. Procedure-A broth microdilution method was used to determine minimal inhibitory concentration (MIC) range and values for MIC50 and MIC90. Resistance of a strain to an antimicrobial agent was determined by use of the breakpoint value when available. Results-Isolates were generally susceptible to penicillin, ampicillin, ceftiofur, gentamicin, apramycin, neomycin, spectinomycin, chlortetracycline, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and most isolates were resistant to clindamycin, tylosin tartrate, and tiamulin regardless of the time period. A substantial increase in resistance to sulfachlorpiridazine, sulfadimethoxine, sulfathiazole, and trimethoprim-sulfamethoxazole was observed, and a minor increase in resistance to oxytetracycline was also detected. Several multiresistance patterns were observed, most frequently among isolates recovered in the 2003 to 2004 interval. Conclusions and Clinical Relevance-Ceftiofur, florfenicol, and enrofloxacin are recommended for treatment of infections caused by P multocida subsp multocida in Spain. Increased frequency of resistance to oxytetracycline and sulfonamide drugs may be a contraindication for their use.

Objective: To evaluate the genetic relatedness and antibiotic sensitivity profiles of Campylobacter coli isolates from sows and piglets housed in an integrated swine production facility. Sample Population: Ninety-nine isolates of Campylobacter coli were collected from 3 sows (Yorkshire-Landrace) and 18 piglets (Yorkshire-Landrace X Duroc or Hampshire) housed in a common farrowing barn. Procedure: When piglets were weaned (21 day of age) fecal samples were collected for the sows and rectal samples were collected from the piglets. Isolation of Campylobacter coli was performed using an enrichment broth and restrictive media under microaerophilic conditions. Results: The Campylobacter coli isolates segregated into 20 ribogroups and exhibited 32 antibiotic susceptibility profiles. The Ribogroup (224-373-S-5) contained 35 isolates from eleven animals. Thirty-eight percent of the animals exhibited a single ribogroup, while 10% of the animals exhibited four ribogroups. No discernible pattern of ribogroup relatedness was observed among the sows and piglets or among littermates. Conclusion: The data suggests a high level of diversity in both ribotypic patterns and antibiotic sensitivity profiles among the Campylobacter coli isolated from related pigs housed in a single facility. Further, no evidence was found for a direct transfer of specific Campylobacter coli ribotypes from a sow to her piglets.

An epidemiologic study of Pasteurella haemolytica serovar 1 (Ph1) in market-stressed feeder calves from 7 farms in eastern Tennessee was conducted. The nasal mucus of each calf was cultured sequentially at the farm of origin (day 0), at an auction market (day 133), and at a feedyard in Texas (days 141, 148, 155, and 169). Of the 103 calves tested, 77 were culture-positive, including 1 on day 0, 1 on day 133, 20 on day 141, 57 on day 148, 50 on day 155, and 14 on day 169. From the 143 Ph1 isolates, 20 enzyme profiles were determined by use of a commercial enzyme system that detects 19 enzymatic reactions; 4 antimicrobial susceptibility profiles were obtained, using the disk-diffusion method, which evaluated susceptibility to 11 antibacterial drugs. All isolates were positive for acid phosphatase and alkaline phosphatase, but were negative for alpha-galactosidase, alpha-mannosidase, beta-glucosidase, beta-glucuronidase, cystine aminopeptidase, N-acetyl-beta-glucosaminidase, and trypsin. Other positive enzyme reactions included: leucine aminopeptidase, 140 Ph1 isolates; phosphohydrolase, 90 isolates; alpha-fucosidase, 63 isolates; esterase (C4), 59 isolates; valine aminopeptidase, 30 isolates; esterase lipase (C8), 24 isolates; beta-galactosidase, 2 isolates; and alpha-glucosidase, chymotrypsin and lipase (C14), 1 isolate each. Thirty-four Ph1 profiles were identified, using combined enzyme and antimicrobial susceptibility profiles. The data indicate that the strains isolated during the feedyard period may have been determined more by farm of origin (P < 0.001) than by habitation with calves from other farms while in the feedyard. The combined enzyme and antimicrobial susceptibility profile method is a rapid and simple epidemiologic technique for tracking Ph1 strains in market-stressed feeder calves.

Plasma and lung tissue pharmacokinetics of danofloxacin calves with naturally induced acute pneumonia were determined in 2 separate studies. A maximal pneumonic tissue concentration of 1.17 microgram/g was achieved 1.8 hours after IM injection of 1.25 mg of danofloxacin/kg of body weight. Pneumonic tissue danofloxacin concentrations were 5.5 times greater than those in plasma at 1 and 2 hours after injection. Cranioventral pneumonic tissue had significantly decreased danofloxacin concentration, compared with that of grossly normal tissue from the caudodorsal part of the lungs at 2 of 6 sample times. After IV injection, the apparent steady-state volume of distribution was 3.44 +/- 1.13 L/kg, and the elimination half-life was 6.26 2.27 hours. Maximal plasma danofloxacin concentration of 0.25 microgram/ml was detected 0.80 hour after IM injection. Bioavailability was 91%. Our findings indicated that a large percentage of danofloxacin is rapidly absorbed after IM administration to calves with acute pneumonia. Extensive tissue penetration was suggested by a high steady-state volume of distribution and was indicated by high concentrations in pneumonic tissue.

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).