Studies on ESBL-producing and multi-drug resistance of Salmonella serovars distributed in Benue State were investigated. A total of four hundred and twenty (420) clinical stool samples, seventy (70) from each local government area were randomly collected from selected hospitals and analyzed for the presence of Salmonella spp. The isolates were characterized using Gram staining and biochemical tests. The result of AP120E biochemical test strip which contained dehydrated bacterial media and biochemical reagents in twenty (20) separate compartments. The result was obtained by evaluation of the compartments due to observed changes in after 24 hours where others were read by adding up reagents (Ferric chloride, Kovacs V.P reagents). The results were analyzed afterwards in accordance with the manufacturer’s software and positive results with ≥89% potential were confirmed as Salmonella spp. Amplified plasmids derived from 18 Salmonella strains recognized were made up of 23,130 base pairs. ESBL (Extended-spectrum beta-lactamases) genes were located on the plasmids. Two of the ESBL genes found were TEM genes and CTX-M (415 bp). Strains such as S. enterica Typhimurium-CP014981.1, S. enterica Enteritidis-CP007325.2, S. enterica Typhimurium-CP024619.1, S. enterica Typhimurium-CP023166.1, S. bongori-FR877557 and S. enterica Enteritidis-TY1 possessed TEM genes where as S. enterica Heidelberg-CP019176.1, S. enterica Typhi-AL513382.1 and S. enterica Typhimurium-MH196335.1 possessed CTX-M. Antibiotic resistance testing was performed using Kirby-Bauer disc diffusion method. The overall percentage susceptibility of the eight antibiotics tested on Salmonella serovars isolates shows that GEN had the highest % susceptibility of 100% followed by NIT (72.2%) and COT (66.7%) before and after plasmid curing. % susceptibility was lower before curing than after curing in CXC, CHL and TET. It was low (5.6%) in ERY while AUG recorded 0% susceptibility. Differences observed in curing status were insignificant (T = 0.33, P > 0.05). The presence of ESBL-producing and multi-drug resistant Salmonella serovars indicates an infection which presents a foremost peril to public health since such infections may be intricate to take care of and may consequently result in death of the infected patients. Constant periodic examination and prevention of drug abuse of antibiotics will assist in ensuring that this trend is curtailed especially in developing nations
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