Fosfomycin represents a potential last-resort treatment option forinfections with extended spectrum β-lactamase-producing (ESBL)Enterobacteriaceae. The present study aimed to evaluate double-drugcombinations of fosfomycin with imipenem, meropenem and doripenemagainst 50 ESBL-producing Klebsiella pneumoniae (K. pneumoniae) andEscherichia coli (E. coli) clinical isolates using the E-test method. Theisolates were collected at Theodor Bilharz Research Institute. ESBLdetection was done using disc diffusion test as a screening test andconfirmed by double disc diffusion test. Susceptibility pattern of the ESBLproducing isolates to different antibiotic classes was tested. Synergy wasdefined as a fractional inhibitory concentration index (FICI) of ≤ 0.5,indifference as 0.5 ≤ FICI ≥ 4 and antagonism as FICI of > 4. E. colirepresented 70% while K.pneumoniae represented 30% of the ESBLproducingisolates. Community acquired infections were frequently highrepresenting 51% of the ESBL- producing isolates. High resistant rateamong ESBL-producing isolates was observed to most antibiotic classesranging from 70% against gentamycin to 100% against amoxicillinclavulanate.Against 50 ESBL-producing E.coli and K.pneumoniae, synergyof fosfomycin with imipenem, meropenem and doripenem was observed for56%, 48% and 50 %; respectively. Antagonism was observed for 4% ofisolates in fosfomycin-meropenem combination. In conclusion fosfomycincan be used in combination with carbapenems to maximize their activity andto decrease the risk of emergence of resistance against ESBL- producingorganisms.