Background: extended spectrum β-lactamase (ESBL) producing gram negative bacilli are becoming a growing problem worldwide with difficulties in designing a national formulary for empirical treatment of gram negative sepsis. Objectives: In this study, we investigated the in vitro activity of Carbapenems, Pipracillin-Tazobactam, Ciprofloxacin alone or in combination with aminoglycosides against ESBL-producing strains isolated from clinical samples. Methods: Three hundred and one ESBL-producing Escherichia coli and K. pneumoniae strains isolated from clinical samples were investigated. Isolates were screened initially for ESBL production using an automated system. All ESBL isolates were further confirmed using the double-disk diffusion method. Results: The overall Piperacillin-Tazobactam susceptibility was 57.9 (64.4% E. coli and 43.6% Klebsiella pneumoniae). Only 29.6 % of ESBLs (24.9% E. coli and 39.6% Klebsiella pneumoniae) were ciprofloxacin susceptible. 98.1% E. coli and 93.1% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Amikacin combination. 73.7% E. coli and 61.4% of Klebsiella pneumoniae were susceptible to Piperacillin-Tazobactam plus Gentamicin combination. 96.7% E. coli and 91.1% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Amikacin combination. 41.2% E. coli and 51.5% of Klebsiella pneumoniae were susceptible to Ciprofloxacin plus Gentamicin combination. Conclusion: ESBLs have high resistance profile against Piperacillin/Tazobactam and Ciprofloxacin. The ESBLs from Oman have similar resistantce pattern as those reported from UK and USA. This resistance decreases when these drugs are combined with Amikacin. All ESBLs are susceptible to Carbapenems. However, carbepenam overuse can lead to emergence of carbapenems resistant gram negative bacilli and ESBLs. Combination of Amikacin plus Piperacillin/Tazobactam is a feasible empirical therapy for ESBLs.