Discovery of novel antigiardiasis drug candidates.

Giardiasis is a severe intestinal parasitic disease caused by Giardia lamblia, which inflicts many people in poor regions and is the most common parasitic infection in the United States. Current standard care drugs are associated with undesirable side effects, treatment failures, and an increasing incidence of drug resistance. As follow-up to a high-throughput screening of an approved drug library, which identified compounds lethal to G. lamblia trophozoites, we have determined the minimum lethal concentrations of 28 drugs and advanced 10 of them to in vivo studies in mice. The results were compared to treatment with the standard care drug, metronidazole, in order to identify drugs with equal or better anti-Giardia activities. Three drugs, fumagillin, carbadox, and tioxidazole, were identified. These compounds were also potent against metronidazole-resistant human G. lamblia isolates (assemblages A and B), as determined in in vitro assays. Of these three compounds, fumagillin is currently an orphan drug used within the European Union to treat microsporidiosis in immunocompromised individuals, whereas carbadox and tioxidazole are used in veterinary medicine. A dose-dependent study of fumagillin in a giardiasis mouse model revealed that the effective dose of fumagillin was ∼ 100-fold lower than the metronidazole dose. Therefore, fumagillin may be advanced to further studies as an alternative treatment for giardiasis when metronidazole fails.

Swine growth promotion with antibiotics or alternatives can increase antibiotic resistance gene mobility potential.

Even though the use of antibiotics for food-producing animals may contribute to the emergence of antimicrobial resistance, antibiotics are still used as growth promoters. Due to consumer and regulatory pressures, the use of alternatives to antibiotics as growth promoters is increasing, thus more information is needed on their capability to disseminate antimicrobial resistance compared to antibiotics. We investigated the impacts of carbadox (antibiotic), copper sulfate and zinc oxide (metals) and mushroom powder (natural product) on the pig fecal resistome and microbiome. Antibiotic resistance gene (ARG) and mobile genetic element (MGE) abundances were measured using a high-throughput qPCR array with 382 primer pairs. Bacterial community composition was determined by 16S rRNA gene sequencing. More ARGs co-occurred with MGEs in the growth promoter group samples than in the control group samples. Community composition could not be linked to resistome in the growth promoter group samples, indicating a potential decoupling of ARGs and phylogeny. Additionally, machine-learning methods aided in defining the community and resistome differences in response to treatments. Since increased ARG mobility potential was the primary response to the dietary additives used in this study, we suggest that ARG mobility should be considered when designing antimicrobial use policies and antimicrobial resistance surveillances.

The effects of dietary additives on faecal levels of Lactobacillus spp., coliforms, and Escherichia coli, and faecal prevalence of Salmonella spp. and Campylobacter spp. in US production nursery swine.

AIMS: In the United States, carbadox and copper sulfate are growth promoters commonly used in combination in nursery swine diets. Our aim was to determine how selected dietary additives affect selected bacterial populations and pathogens in nursery swine, and compare to larch extract, which contains potential antibacterial activities. METHODS AND RESULTS: Piglets were weaned and sorted into one of the four treatments: (i) basal diet without antimicrobials; (ii) basal diet with carbadox + copper sulfate; (iii) basal diet + 1000 ppm larch extract; or (iv) basal diet + 2000 ppm larch extract. Diets were fed for a 4-week period after weaning. In both trials, the carbadox + copper sulfate group consumed more feed over the 4-week period relative to the other three diet groups (P < 0.05), but did not gain significantly more weight. Faecal shedding of Salmonella spp. was not affected by dietary supplement in either trial, but faecal shedding of Campylobacter spp. was the lowest for the carbadox + copper sulfate diet. In faecal samples collected at the end of each trial, Lactobacillus spp. cell counts for the basal and larch extract diets were nearly 1.0 log(10) g(-1) faeces greater (P < 0.05) than the carbadox + copper sulfate group, whereas the coliforms and Escherichia coli were nearly 1.0 log(10) g(-1) faeces lower (P < 0.05). CONCLUSIONS: Compared to basal fed animals, supplementation with carbadox + copper sulfate significantly altered faecal E. coli, coliform bacteria and Lactobacillus spp. Larch extract has no benefit up to 0.2% of diet in regard to pathogen shedding, whereas carbadox + copper sulfate decreased faecal shedding of Campylobacter spp. SIGNIFICANCE AND IMPACT OF THE STUDY: Current swine management practices in the United States may be beneficial to managing Campylobacter spp. shedding in nursery swine, but also result in significant changes in the resident gastrointestinal microflora.

Bacillus subtilis: a potential growth promoter in weaned pigs in comparison to carbadox.

The study was conducted to investigate the efficacy of a probiotic Bacillus subtilis strain on growth performance, diarrhea, systemic immunity, and intestinal health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli and to compare the efficacy of B. subtilis with that of carbadox. Weaned pigs (n = 48, 6.17 ± 0.36 kg body weight [BW]) were individually housed in disease containment rooms and randomly allotted to one of four dietary treatments: negative control (NC, control diet without E. coli challenge), positive control (PC, control diet with E. coli challenge), and supplementation of 50 mg/kg of carbadox (antibiotic growth promotor [AGP]) or 2.56 × 109 CFU/kg of B. subtilis probiotics (PRO). The experiment lasted for 28 d with 7 d before and 21 d after the first E. coli inoculation. Fecal and blood samples were collected on days 0, 3, 7, 14, and 21 post inoculation (PI) to analyze ß-hemolytic coliforms and complete blood cell count, respectively. Diarrhea score was recorded daily for each pig to calculate the frequency of diarrhea. All pigs were euthanized at day 21 PI to collect jejunal and ileal mucosa for gene expression analysis. Pigs in AGP had greater (P < 0.05) BW on days 7, 14, and 21 PI than pigs in PC and PRO groups. Supplementation of PRO enhanced pigs' BW on day 21 PI compared with the PC. Escherichia coli F18 challenge reduced (P < 0.05) average daily gain (ADG) and feed efficiency from day 0 to 21 PI, while supplementation of carbadox or PRO enhanced ADG and feed efficiency in E. coli F18-challenged pigs from day 0 to 21 PI. Pigs in AGP and PRO groups had reduced (P < 0.05) frequency of diarrhea throughout the experiment and fecal ß-hemolytic coliforms on day 7 PI than pigs in the PC. Pigs in PRO had greater (P < 0.05) gene expression of CLDN1 in jejunal mucosa than pigs in the PC. Supplementation of carbadox or PRO reduced (P < 0.05) the gene expression of IL6 and PTGS2 in ileal mucosa of E. coli-infected pigs compared with pigs in the PC. Pigs in the PRO group had lower (P < 0.05) white blood cell number and neutrophil count, and serum haptoglobin concentration on day 7 PI, and less (P < 0.05) monocyte count on day 14 PI, compared with PC. In conclusion, supplementation of probiotic B. subtilis could enhance disease resistance and promote the growth performance of weaned pigs under disease challenge conditions. The potential mechanisms include but not limited to enhanced gut barrier integrity and local and systemic immune responses of weaned pigs.

Collateral effects of antibiotics: carbadox and metronidazole induce VSH-1 and facilitate gene transfer among Brachyspira hyodysenteriae strains.

Brachyspira hyodysenteriae is an anaerobic spirochete and the etiologic agent of swine dysentery. The genome of this spirochete contains a mitomycin C-inducible, prophage-like gene transfer agent designated VSH-1. VSH-1 particles package random 7.5-kb fragments of the B. hyodysenteriae genome and transfer genes between B. hyodysenteriae cells. The chemicals and conditions inducing VSH-1 production are largely unknown. Antibiotics used in swine management and stressors inducing traditional prophages might induce VSH-1 and thereby stimulate lateral gene transfer between B. hyodysenteriae cells. In these studies, VSH-1 induction was initially detected by a quantitative real-time reverse transcriptase PCR assay evaluating increased transcription of hvp38 (VSH-1 head protein gene). VSH-1 induction was confirmed by detecting VSH-1-associated 7.5-kb DNA and VSH-1 particles in B. hyodysenteriae cultures. Nine antibiotics (chlortetracycline, lincomycin, tylosin, tiamulin, virginiamycin, ampicillin, ceftriaxone, vancomycin, and florfenicol) at concentrations affecting B. hyodysenteriae growth did not induce VSH-1 production. By contrast, VSH-1 was detected in B. hyodysenteriae cultures treated with mitomycin C (10 microg/ml), carbadox (0.5 microg/ml), metronidazole (0.5 microg/ml), and H(2)O(2) (300 microM). Carbadox- and metronidazole-induced VSH-1 particles transmitted tylosin and chloramphenicol resistance determinants between B. hyodysenteriae strains. The results of these studies suggest that certain antibiotics may induce the production of prophage or prophage-like elements by intestinal bacteria and thereby impact intestinal microbial ecology.

Mutagenicities of carbadox and olaquindox--growth promoters for pigs.

Carbadox and olaquindox were examined for mutagenicities in the repair tests with Bacillus subtilis (rec assay) and Salmonella typhimurium (uvr assay) and in the reverse mutation test (TA100 and TA98 of S. typhimurium). Both compounds were positive in the rec and uvr assays, and were highly mutagenic for strains TA100 and TA98. Carbadox was about 6 times move mutagenic than olaquindox in the absence of S9 mix. When incubated in S9 mix or bacterial cytosol (BC) mix for various times at 37 degree C, carbadox was found to lose its mutagenic activities easier than olaquindox. The mutagenicity of carbadox was almost inactivated at 10 min after incubation with S9 mix, but olaquindox still retained its activities even at 20 min. While carbadox required 20 min to be inactivated in BC mix, olaquindox was not completely inactivated even if incubated for 60 min.

The mutagenic action of quindoxin, carbadox, olaquindox and some other N-oxides on bacteria and yeast.

The mutagenic action of 3 coccidiostatic chinoxaline-N-oxide derivatives, quindoxin, carbadox and olaquindox, was investigated by Luria and Delbrück's fluctuation test, with Klebsiella pneumoniae and Escherichia coli K12 as test organisms. These compounds were mutagenic at very low concentrations (2 X 10(-5)--500 X 10(-5) mmole/l). In the Ames test they showed a mutagenic action without metabolic activation with Salmonella typhimurium TA98 and TA100 at concentrations of 0.001-0.1 mmole/l in the top agar. Hence, these compounds cause both base-pair substitutions and frame-shift mutations. When Saccharomyces cerevisiae D4 was cultivated in the presence of the compounds, an increase in the mitotic gene conversions was observed. Certain other N-oxides also showed a mutagenic action in the fluctuation test. With Klebsiella pneumoniae, 4-nitroquinoline 1-oxide was mutagenic at a concentration of 0.005 mmole/l, quinoline 1-oxide at 10 mmole/l and benzofuroxan at 0.01 mmole/l. In this test no mutagenic action was found with 4-nitropyridine 1-oxide, pyridine 1-oxide or 4-picoline 1-oxide. With Salmonella typhimurium TA98 and TA100, 4-nitroquinoline 1-oxide, benzofuroxan and 4-nitropyridine 1-oxide were mutagenic, whereas quinoline 1-oxide, pyridine 1-oxide and 4-picoline 1-oxide were not. In contrast, with the fluctuation test, 4-nitroquinoline 1-oxide appeared to be more mutagenic than quindoxin, carbadox and olaquindox in the plate incorporation test.

Sister-chromatid exchange in Chinese hamster V79 cells exposed to quindoxin, carbadox and olaquindox.

Quindoxin, carbadox and olaquindox were subjected to the Chinese hamster V79/SCE test. All three compounds demonstrated a dose-dependent increase of SCE frequencies.

Mutagenicity screening of feed additives in the microbial system.

18 feed additives were tested for DNA-modifying effects by the repair test named "rec-assay" with Bacillus subtillis H17 (rec+) and M45 (rec-), and for mutagenicity with Escherichia coli WP2 hcr and 5 Salmonella typhimurium tester strains with the use of a top-agar overlay method. Carbadox, furazolidone, panazon and zoalene were positive in both assays. The former 3 were mutagenic for TA100, TA98 and WP2 hcr, while zoalene was mutagenic for all strains. These 4 compounds did not require a metabolic activation for their mutagenic activities. Nicarbazin was weakly mutagenic for TA1538 and TA98 with and without S9 mix. Amprolium and caprylohydroxamic acid also showed very weak mutagenicities only for TA100 with S9 mix and for WP2 hcr with and without S9 mix, resp. The mutagenic activities of carbadox, furazolidone and panazon for TA100 were reduced only by the addition of S9 mix, but not by S9 fraction or blood, whereas that of zoalene was decreased by any of the 3 factors.

Cytogenetic effects of quinoxaline-1,4-dioxide-type growth-promoting agents. I. Micronucleus test in rats.

The cytogenetic activities of 3 growth-promoting agents carbadox, olaquindox and cyadox were examined by the micronucleus test. These chemicals were administered i.p. to male Wistar rats 30 and 6 h before they were killed. Single-dose levels were 5, 10, 15, 30, 60, 90, 120 and 240 mg/kg for carbadox; 30, 60, 90, 120 and 240 mg/kg for olaquindox; and for cyadox 30, 60, 120 and 240 mg/kg. Over the entire dose range tested, carbadox induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes in the rat bone marrow, whereas similar activity of olaquindox started at a dose of 2 X 60 mg/kg. The effect of cyadox was very low even at the highest dosage tested. Further testing of the genotoxicity of this class of chemicals is required. The genetic activity of the solvent used (dimethyl sulfoxide) is briefly discussed.

Cytogenetic effects of quinoxaline-1,4-dioxide-type growth-promoting agents. III. Transplacental micronucleus test in mice.

The growth-promoting agents carbadox and olaquindox were active in the mouse transplacental micronucleus test, whereas cyadox was ineffective. Chemicals were administered p.o. and i.p. at a dose of 100 mg/kg and the effect was observed 18 h after treatment. The effects observed in fetal liver were parallel to those in maternal bone marrow, but fetal tissue was approximately 2-3 times more sensitive.

Minimal inhibitory concentrations of five antimicrobials against Treponema hyodysenteriae and Treponema innocens.

The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method. The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T. hyodysenteriae, followed by carbadox. Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T. hyodysenteriae isolates. Isolates of T. innocens were more sensitive to the various antimicrobials. Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin.

Pathological effects of carbadox in pigs with special emphasis on the adrenal.

Weaned pigs, 4-weeks-old, were divided into 6 groups of 13 animals each, which received 0, 25, 50, 100, 150 and 200 ppm (mg per kg) of carbadox medicated feed, respectively. After 5 and 10 weeks of carbadox administration, three and two pigs, respectively, of each group were necropsied. After 5 weeks treatment, gross lesions were seen in pigs receiving 50 ppm or more. The main features were retarded growth, dehydration with dry contents in the intestine, especially in the colon and findings suggestive of pica. The severity of lesions increased with higher dosages. After 10 weeks, the same changes, though much more pronounced, were observed at 100 ppm or higher dosages. After 5 weeks histological changes in the adrenals were found at 50 ppm treatment and upwards. The common feature was a hydropic appearance of the glomerular zone. In the 50 ppm group one out of three and, in the higher dosed groups, all pigs showed these changes. There was a dose-response effect. At 100 ppm or more an enlargement of the glomerular zone was observed, resulting in narrowing of the fascicular layer. The adrenal capsule was slightly thickened and contained cells with PAS-positive granules. After 10 weeks, changes were found at 25 ppm dosage and higher. In the 25 and 50 ppm group half of the pigs had hydropic changes of the glomerular zone. In the higher dosed groups there were also chronic lesions. The outer part of the glomerular zone had become fibrotic. With 150 ppm or more the hydropic changes had extended into the fascicular layer, with development of hyperplastic nodules. This led to disappearance of zonal differentiation. From 100 ppm dosage, many richly granulated PAS-positive cells were present in the thickened capsule, more numerous and more granulated than after 5 weeks treatment. From this study, it can be concluded that carbadox may induce adverse effects on the adrenal in growing pigs at therapeutic (100 to 150 ppm) and feed-additive doses (50 ppm). Even at lower doses (25 ppm), mild lesions were found. The grade of lesions was positively correlated with the duration of exposure to this growth promoter.

The effects of a dietary antimicrobial on the biological half-life of chenodeoxycholic acid and plasma bile acid concentration patterns in the young pig.

Carbodox (CX), an antimicrobial agent, was fed at 0 or 58 ppm in a 19.5% crude protein corn-soybean metal diet to young pigs (12 to 15 kg). Radiolabeled chenodeoxycholic acid (CDC) was infused into the hepatic portal vein; after each of the subsequent six meals, blood samples were collected from the anterior vena cava (VC) and the hepatic portal (HP) veins. For the first 5 min after CDC infusion, the level of radioactivity in the CX pigs was significantly lower in the HP plasma and the slopes of the two curves of the plasma activity for the first hours were significantly different. The plasma bile acid concentrations (as measured by radioactivity) were significantly higher in the CX-treated animals following all meals. The biological half-life of CDC was 6.4 d in the controls and 5.7 d in the CX pigs. The increased rate of excretion was significant. These data indicate that bile acid metabolism in the young pig was significantly affected by feeding a subtherapeutic level of the antimicrobial CX.

Effect of carbadox on net absorption of ammonia and glucose into hepatic portal vein of growing pigs.

Chronic cannulas were placed into the hepatic portal vein, ileal vein and carotid artery of growing pigs trained to consume their daily allowance of 1.2 kg of feed (16% protein corn-soybean meal basal diet) in a single meal. The average preoperative BW of pigs was 44.7 kg for Trial 1 (three pigs) and 35.3 kg for Trial 2 (seven pigs). In Trial 1, net absorption of ammonia (NH3) and glucose into the portal vein was determined three times at weekly intervals. The net portal absorptions were derived by multiplying the porto-arterial plasma concentration difference of NH3 and glucose by portal vein plasma flow rate estimated with the p-aminohippuric acid indicator-dilution technique. Differences in the net portal absorptions of NH3 and glucose among the three weekly measurements were small (P greater than .05). In Trial 2, the first sequence of net portal absorption measurements was conducted when pigs were fed the basal diet, and the second sequence of measurements was conducted after the pigs had been fed the diet supplemented with 55 ppm of carbadox for 7 d. Carbadox supplementation reduced (P less than .05) plasma NH3 concentration in portal plasma during the 2.5-h to 5-h postprandial period and decreased (P less than .05) net portal absorption of NH3 during the 2.5-h to 4-h postprandial period. Carbadox, however, did not affect (P greater than .05) net portal absorption of glucose. We suggest that carbadox suppresses the production of cell-toxic NH3 by intestinal microorganisms and, thus, reduces the injury and turnover of intestinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro muscle cell proliferation and protein turnover as affected by serum from pigs fed antimicrobials.

The effect of antimicrobial supplementation of pigs on the capacity of their sera to influence proliferation and protein turnover in cultured muscle cells was evaluated. Mitogenic activity of sera increased when pigs were fed ASP250 (P less than .005) or carbadox (P less than .001), whereas the mitogenic activity of serum from pigs receiving the basal diet remained unchanged (P = .5). Additionally, sera from ASP250-fed pigs significantly decreased (P less than .001) total cellular protein degradation compared with sera obtained from the same pigs prior to supplementation. Neither ASP250 nor carbadox stimulated proliferation of myogenic cells when added to the culture media. Inclusion of ASP250 in swine diets altered the composition of their sera in a way that stimulated muscle cell proliferation and reduced the rate of protein degradation in cultured myogenic cells. Likewise, the inclusion of carbadox in swine diets increased the ability of their sera to stimulate cultured muscle cell proliferation.

Influence of carbadox on fasting oxygen consumption by portal vein-drained organs and by the whole animal in growing pigs.

Fasting O2 consumption by the whole animal (W) and by portal vein-drained organs (PVDO) during the 24- to 30-h postprandial period were measured in seven growing pigs (36.1 +/- 2.3 kg) with catheters chronically placed in the hepatic portal vein, ileal vein, and carotid artery trained to consume 1.2 kg of a 16% CP corn soybean meal basal diet (B) once daily. The pigs were placed individually into an open-circuit, indirect calorimeter and connected to an arteriovenous (A-V) O2 difference analyzer for hourly simultaneous measurements of O2 consumption by W and PVDO. The PVDO O2 consumption was calculated by multiplying the A-V O2 difference by the portal vein blood flow rate derived from constant infusion of a p-aminohippuric acid solution into the ileal vein. After the initial series of hourly measurements, four pigs remained on the B diet and three pigs were fed a B + 55 ppm carbadox diet. Seven days later, the second series of measurements was made. In pigs fed the diet with carbadox added, the hourly W O2 consumptions were not different (P greater than .05) between the initial and second series and averaged 7.5 mL.min-1.kg of BW-1. However, the A-V O2 differences (mL/dL) were reduced (P less than .05) from 4.6 to 4.0 at 24 h, 4.8 to 4.0 at 25 h, and 4.6 to 4.0 at 29 h postprandial and the fractions of W O2 consumption used by PVDO (percentage) were reduced (P less than .05) from 28.6 to 21.6 at 26 h and 25.2 to 18.2 at 27 h postprandial.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a dietary antimicrobial (carbadox) on liver cholesterol 7 alpha-hydroxylase activity and bile acid patterns in the young pig.

Two experiments were conducted to investigate the effects of the antimicrobial carbadox (CX) on bile acid metabolism in the young pig. The pigs were fed a fortified, 19.5% crude protein, corn-soybean meal diet without or with 55 ppm CX. In Exp. I pigs were fed the diets for 28 d, then the level of activity of hepatic cholesterol 7 alpha-hydroxylase (CH-7 alpha), the rate-limiting enzyme of bile acid metabolism, was measured. The CX-fed pigs gained faster (P less than .05) and more efficiently (P less than .05) and had lower (P less than .02) CH-7 alpha activity than the control pigs. In Exp. II, pigs ranging in weight from 12 to 15 kg were fitted with indwelling catheters in the hepatic portal (HP) and anterior vena cava (VC) veins. Radiolabeled chenodeoxycholic acid (CDC) was infused into the HP and blood samples from both veins were taken at meal time and hourly for 6 h following six meals over 3 d. Bile was collected 14 d after infusion. Concentrations of lithocholic acid (LC) in the bile and hyodeoxycholic acid (HDC) in the plasma were reduced by dietary CX. Dietary CX did not significantly affect metabolism of plasma CDC or hyocholic acid (HC) as measured by radioactivity. Meal time (0800 vs 1600) affected (P less than .05) plasma CDC radioactivity at all times and the level of HDC radioactivity 2 h post-prandial. There was a meal time X dietary treatment interaction (P less than .02) on plasma HC radioactivity 2 h post-prandial. These data suggest that dietary CX inhibited intestinal microbial degradation of CDC and HC.

Efficacy of tiamulin as a growth promotant for growing swine.

A study involving 244 pigs initially averaging 13 kg was conducted at two stations to evaluate tiamulin as a growth promotant for growing swine. In each experiment, four replicate pens of five (Exp. 1) or six (Exp. 2) pigs/pen were used to evaluate each treatment. In Exp. 1, pigs were fed 0, 11, 22 or 44 ppm tiamulin from 15 to 58 kg, then fed a nonmedicated control diet for the remainder of the experiment (to 95 kg). In Exp. 2, pigs were fed 0, 2.75, 5.5, 11 or 22 ppm tiamulin from 11 to 56 kg, followed by the nonmedicated control diet (to 95 kg). In each experiment, carbadox (55 ppm) was included as a positive control and was fed to an average weight of 35 kg, followed by the control diet. Averaged across all dietary levels, tiamulin resulted in a 14.1% improvement in gain and a 5.7% improvement in feed:gain ratio during the first 28 to 35 d of the experiment (to 30 kg). These improvements were slightly less than those resulting from the feeding of carbadox during the same period (21.5 and 6.9%, respectively). From 13 to 57 kg, pigs fed tiamulin gained 11.6% faster and 3.1% more efficiently than did controls. Over the entire experiment (13 to 95 kg), tiamulin-fed pigs gained 5.7% faster than did controls, even though the tiamulin was withdrawn at 57 kg body weight. Growth rate from 13 to 57 kg plateaued at the 11-ppm dietary level of tiamulin; whereas, feed:gain ratio plateaued at the 22-ppm level. The results indicate that tiamulin is an effective growth promotant for growing swine.

Effect of dietary supplementation with vitamin C or carbadox on weanling pigs subjected to crowding stress.

A 2 X 3 factorial arrangement was used in each of two trials with two levels of floor space allowance (.25, .13 m2/pig) and three dietary treatments (basal, basal + 660 ppm vitamin C, basal + 55 ppm carbadox). The reduction in floor space allowance was achieved in trial 1 by doubling the number of pigs/pen from eight to 16 and in trial 2 by reducing the size of pens by half. An 18% protein starter diet was used as the basal diet. Total numbers of pigs used were 216 in trial 1 and 144 in trial 2. Pigs were weaned between 4 and 5 wk of age (7.5 kg average wt) and fed ad libitum for 28 d. Reducing floor space allowance caused a (P less than .05) reduction in weight gain of weanling pigs in both trials. When the reduction of floor space allowance was done by increasing number of pigs/pen (trial 1), pigs responded with a significantly reduced feed intake with no change in efficiency of feed utilization. However, when floor space allowance was reduced by changing the size of the pen (trial 2), feed intake of pigs was not affected but efficiency of feed utilization was reduced significantly. Neither form of crowding affected vitamin C concentration in adrenal glands and weights of adrenal glands, spleen and thymus. Dietary supplementation of carbadox, but not vitamin C, produced significantly greater weight gain, feed efficiency, and spleen weight of pigs in both trials. Although there was no interaction between crowding and dietary treatment in affecting the performance of pigs, supplemental carbadox improved the performance of crowding-stressed pigs by maintaining an adequate level of feed intake and improving feed efficiency, whether crowding was caused by increased pig density or by reduced pen size. No significant differences in phytohemagglutinin (PHA) skin test response or in the neutrophil-to-lymphocyte ratio (N/L) were observed among treatments in trial 1, while a significantly reduced response to PHA and a higher N/L were detected in crowding-stressed pigs in trial 2.