A total of 55 stool samples were collected, out of which 25 clinical isolates of Salmonella enterica serotypes from the Hospital in the South east Nigeria were investigated on for βlactamase enzyme production and the presence of mutation in the gyrase A gene, an enzyme that codes for point mutation and resistant in quinolone, using phenotypic and molecular methods. The presence of β-lactamase was revealed using Nitrocefine sticks and Double disc Synergy Test was used to detect ESBL'S positive Isolates. Analysis reveals that all the S.enterica had somatic and flagellated antigenic properties, out of which 13(52%) of the isolates were ESBL's positive, while 20(80%) of S.enterica serovars produced β-lactamase enzyme and 5(20%) were negative for β-lactamase. The polymerase chain reaction revealed the absence of double mutation in parC gene and also the presence of point mutation in gyr Agene in the DNA chromosome of 9(36%) of the isolates. From this study Levofloxacine and Ceftriaxone still retains the potency as the drug of choice for Salmonellosis as ciprofloxacin had increased MIC's of 3.125µg/ml. This is first report of detection of mutation in Gyr A enzyme in S.enterica , that codes for point mutation in the Quinolone Resistant Determining Region( QRDR'S) in Southeast Nigeria.