The goal of this dissertation was to evaluate silver ion as a potential antibiotic alternative in broiler chickens. For this purpose, four experiments were conducted to evaluate silver ion in terms of in vitro antimicrobial efficacy, in vivo potential toxicity, and to evaluate its potential growth promoting effect. In experiment 1, an in vitro antimicrobial efficacy experiment was conducted using two separate silver carbene complexes (SCCs) with different carrier molecules, (SCC1 with a methylated caffeine backbone and SCC22 with a dichloroimidazolium backbone), and silver acetate were investigated against four important animal and human pathogen species. Both SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects against multidrug resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli 1568 (swine isolates), and the poultry field isolates Salmonella Heidelberg, Salmonella Enteritidis, and Salmonella Montevideo. Ten hours incubation of CP with 40 ug/mL of all three products showed down regulation of virulence genes plc and netB, suggesting viable cells and silver can modulate the virulence. These data suggest that SCCs may represent a novel class of broad-spectrum antimicrobial agents, which may be used to reduce the burden of pathogenic bacteria in the gastrointestinal tract of poultry. In experiment 2, a preliminary in vivo study was conducted to investigate the potential acute oral toxicity of SCC1, SCC22, and AgAc on 300 7-day old broiler chickens in 2 independent replicates trials. Compared to the control and SCCs, single administration of silver acetate at a dose 1000 mg/kg BW reduced (P < 0.05) BW after 7 and 14 days of administration, although the birds showed normal weight gain compared to the control. No adverse effects of SCC1 and SCC22, and silver acetate on relative organ weight of vital internal organs, bone mineralization, or plasma enzymes (ALT, ALP, and GGT) and metabolites (blood urea nitrogen, creatinine, and total bilirubin) were noted compared to control group. Study 3 was a Clostridium perfringens challenge study to evaluate the potential effect silver acetate (AgAc) on starter broiler chicken performance and necrotic enteritis development. The in vivo efficacy of AgAc delivered either by adding into the feed (as a prophylactic model) or via drinking water (as a treatment model) during necrotic enteritis challenge and Infectious Bursal disease immunization was evaluated in two experiments. Whether AgAc was added into the feed (for 21 d) or in the water (4 d), there were no differences (P > 0.05) seen in bird performance, Clostridium perfringens enumeration, and lesion score compared to the positive and negative controls. These results suggest limitation effect of silver acetate on performance and reduce intestinal Clostridium perfringens colonization in broiler chickens, although the in vitro efficacy results showed bacteriostatic and bactericidal different enteric poultry pathogens. In experiment 4, we further evaluated the potential effect of silver acetate in comparison to antibiotic and its selected alternatives (probiotic and prebiotic) on performance, energy and amino acids digestibility, intestinal histology, total bone mineral content (BMC) and density (BMD), and hepatic glutathione. Dietary supplementation of AgAc at 10 and 50 ppm did not show different effects on performance compared to the Control group during all production phases. Dietary AgAc supplemented at 250 ppm showed reduced BW (P < 0.05) compared to the Control, BMD50, and dietary AgAc at 10 and 50 ppm. Overall, using silver acetate in broiler diets could result in adverse effects at concentrations of 250 ppm, and lower concentrations did not show improvement on performance over the control or BMD50.
