الفهرس 
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Abstract
Multidrug-Resistant Gram-Negative Organisms Are The Leading Cause Of Mortality And Morbidity. Antibiotic Combinations Have Been Demonstrated To Be Effective Against Multi-Drug Resistant Or Extensively Drug Resistance Pathogens. The In-Vitro And In-Vivo Effects Of Amikacin And Imipenem Combination Have Been Investigated Against Resistant Pathogens Isolated from Different Infections. The Antimicrobial Susceptibility Of The Isolated Pathogens Was Tested Against Different Antibiotics. It Was Found That Piperacillin/Tazobactam (33.3%) And Gentamycin (34%) Were The Most Effective Drugs. The In-Vitro Studies Were Carried Out By Checkerboard Technique And Time-Killing Assay.
The Tested Drug Combination Of Amikacin And Imipenem Showed Significant Decline In Colonies Counts (P Value<0.5). In-Vitro Studies Indicated Synergistic Effect Of The Tested Combination. Morphological Changes In selected Resistant Isolates Due To Combination Or Monotherapy Was Examined By Scanning Electron Microscope. The Examination Revealed More Cell Shrinkage And Outer Membrane Disruption When Using Drug Combination Than Monotherapy. Conventional PCR And Real-Time PCR Techniques Were Used In Genetic Studies To Assess The Effectiveness Of Drug Combination. The Blaimp And Aac (6’)-Ib Were Detected In 57.3% And 42% Of The Isolates, Respectively. The Treatment With 0.25 Minimum Inhibitory Concentration Of Imipenem And 0.5 Minimum Inhibitory Concentration Of Amikacin Showed Lowest Gene Expression.
The In-Vitro Assays Showed Synergistic Activity Between Combination Of The Tested Drugs With Fractional Inhibitory Concentrations (Ficis) Of ≤0.5. The Therapeutic Efficacy Of These Combination Was Evaluated By Using In-Vivo Mouse Model That Injected By Tested Strains Intraperitoneal. This Model Confirmed The Synergistic Effect For This Combination. Finally, The Combination Of Imipenem And Amikacin Demonstrated Many Advantages Over Monotherapy By In-Vitro Or In-Vivo Studies. In The Future; They May Be A Treatment Option For MDR Or XDR Pathogens.