The current study aimed to control the bacterial infection associated with summer mortalities in Nile tilapia. For determination to the sensitivity of the isolated bacteria to different antimicrobials; Aeromonas Veronii (A. veronii) strian (HY1, HY2, HY3, HY4 and HY6), Citrobacter freundii (C. freundii), Proteus vulgaris (P. vulgaris) and pseudomonas flurosence (P. flurosence) isolates were tested for antimicrobial sensitivity and antimicrobial resistant genes. In order to verify the result of antibiotic sensitivity test; experimental trial was performed to determine the effect of Florofenicol and Erythromycin against infection of O. niloticus with the different pathogenic bacteria (4 strains of A. veroni (A(HY2), A(HY3), A(HY4) and A(HY6)), C. freundi, P. flourosence and P. vulgaris). The results revealed that all tested bacterial isolates were 100 % sensitive to florfenicol and erythromycin, 50% sensitive to gentamycin, 25 % sensitive to nalidixic acid and sulphamethoxazole-trimethoprim, while sensitivity to other antibiotic discs was 0%. In addition, all bacterial isolates were 100% resistant to oxytertracycline and tetracycline lincomycin, ofloxacillin and penicillin, 87.5% resistant to ampicillin, 75% resistant to sulphamethoxazole-trimethoprim, 62.5% for naldixic acid and 37.5% for gentamycin . The survivability of challenged medicated fish with erythromycin ranged from 45-91.7%. Where, the survival % in HY3 infected groups was the highest recording; 91.7% followed by C. freundii (87.5%), HY6 (83.3 %) and P. vulgaris (81.3%). It was concluded that both erythromycin and florfenicol proved effective in treating bacterial infections associated with summer mortality syndrome. Furthermore, a number ofbacteria have multiple drug resistance attributing to the misuse of antimicrobial agents.