The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50, values of SDM and SDM for B bronchiseptica were 4 and 1 microgram/ml, respectively; for P multocida, 16 and 8 microgram/ml, respectively; and for A pleuropneumoniae, 16 and 8 microgram/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains). The MIC of the combinations were similar for the 2 types of strains.

Efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by beta-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (S/A, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with S/A resulted in a statistically significant (P < 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of S/A-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P < 0.07), macroscopic pathologic features of the whole lung (P < 0.1), and histopathologic variables (P < 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced grain-negative lung infection in foals.

Objective-To investigate accumulation of extracellular adenosine (ADO) by equine articular chondrocytes and to compare effects of adenosine kinase inhibition and adenosine deaminase inhibition on the amount of nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated chondrocytes. Sample Population-Articular cartilage from metacarpophalangeal and metatarsophalangeal joints of 14 horses. Procedure-Chondrocytes were cultured as monolayers, and cells were incubated with LPS, the adenosine kinase inhibitor 5'-iodotubercidin (ITU), or the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3- nonyl)adenine hydrochloride (EHNA). Concentrations of ADO in cell supernatants were measured by use of reverse-phase high-performance liquid chromatography. Effect of inhibition of enzymatic metabolism of ADO on induced NO production was evaluated by exposing cells to a combination of LPS and ITU or LPS and EHNA. Results-Articular chondrocytes accumulated extracellular ADO when exposed to LPS or ITU. Chondrocytes exposed to ITU accumulated ADO in a time-dependent manner. Unstimulated chondrocytes did not accumulate ADO. Similarly, EHNA alone did not produce detectable ADO concentrations; however, addition of EHNA and ITU resulted in a synergistic effect on accumulation of ADO. Lipopolysaccharideinduced NO production was more effectively suppressed by exposure to ITU than to EHNA Conclusions and Clinical Relevance-Equine articular chondrocytes release ADO in response to the proinflammatory stimulus of bacterial LPS. Inhibition of the metabolism of ADO increases accumulation of extracellular ADO. Autocrine release of ADO from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions, and pharmacologic modulation of these pathways in joints of arthritic horses could be a potential method of therapy.

Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire X Landrace X Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time. Treatment with T-2 toxin induced microcytic hypochromic anemia, increased numbers of circulating metarubricytes and decreased absolute numbers of lymphocytes. Hepatocellular lesions in barrows of the AF and the AF plus T-2 groups (2 and 4, respectively) were compatible with aflatoxicosis. When fed in combination, each toxin appeared to have a sparing action on certain effects of the other, and the responses elicited were either additive or less than additive.

Combination therapy of antibiotics is leading to improved efficacy or safety profiles with decrease emergence of bacterial resistance. Because of this benefit, many of antibacterial combinations have been used in veterinary practice for the past few decades. The purpose of this study was to examine the in vitro activity of an amoxicillin alone and in combination with other antibiotics against pathogenic bacteria of fish origin. Based on the fractional inhibitory concentration (FIC) index (FIC less-than or equal to 0.5), a synergistic interaction was shown in combination of florfenicol with amoxicillin or cefuroxime. The combination of florfenicol and amoxillin showed higher antibacterial activity than that of florfenicol and cefuroxime. Ratio of amoxicillin and florfenicol in combination was 1 : 1, which showed the antibacterial activity against bacterial isolates of fish as compared with other ratios. A synergetic effect of the combination (amoxicillin and florfenicol) was further confirmed in the time-kill curve study. The study showed a better in vitro antibacterial activity of a 1 : 1 combination of amoxicillin and florfenicol than the individual antibacterial against bacterial isolates of fish. In conclusion, the combination of florfenicol and amoxicillin may serve as a potential antibacterial therapy in fishes infected pathogenic bacteria.