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Abstract Background: Probiotic bacteria have been investigated in the prevention and treatment of various diseases. The current study was undertaken to determine the antimicrobial effect of many probiotic lactobacillus strains against multidrug resistant (MDR) klebsiella isolates by using their cell free supernatants (CFS) in vitro. First screening, for detection which two types of supernatants will be used to compare their antimicrobial effects alone and in combination with cefoperazone as antibiotic on all MDR isolates by agar well diffusion assay. Results: Screening on ten MDR isolates revealed that the mean of inhibition zones of lactobacillus helveticus CFS was (13 mm) and lactobacillus rhamnosus CFS (12 mm). Detection of antimicrobial effects of the selected two strains L. helviticus and L. rhamnosus versus highest concentration of cefoperazone at (MIC = 512 og/ml) on the 50 Klebsiella MDR isolates showed significant increase in mean value of inhibition zones with (14.32 mm) ,(13.3 mm) and (11.64 mm) for L. helviticus CFS, L. rhamnosus CFS and cefoperazone respectively with statistically highly significant P value (<0.001). Effect of combination of cefoperazone with both L.helviticus and L.rhamnosus showed significant decrease of mean value of inhibition zones obtained by these combinations versus lactobacillus helveticus CFS and Lactobacillus rhamnosus CFS individually denoting less inhibitory effect of this combinations on isolates. Conclusion: The antimicrobial efficiency of using cell free supernatants of specific species indicates that these therapies may provide the basis to find out the alternative strategies against resistant pathogens |