الفهرس 
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Abstract
Pseudomonas aeruginosais anon-lactosefermenter that hasemerged asan important opportunistic pathogenover the pastdecade. Itcausesopportunistic health care associated infections in patients who arecritically ill or immunocompromised. Its multiple drug resistance is common andis increasing day by day which makes treatment of itsinfections difficult and sometimes unachievable.The aim of the present work was toinvestigate the antimicrobial resistance profiles and molecular resistance mechanisms of Pseudomonasnosocomial isolates obtained from human specimens associated with hospital environment from some hospitals in Alexandria andDamanhour area.Our aim was alsoto test the efficacy of some antibiotic combinationsagainst some selected isolates.Eighty threeclinical isolates obtained from different specimens were used in this study. These isolates were identified, by macroscopicalexamination of the colony morphology, the classical microscopical examination and some important biochemical tests.The resistance pattern of the collected isolates against seventeen selected antibiotics belonging to several classes and having different modes of action was evaluated using the standard disc agar diffusion technique.Most of these isolates were highlyresistant to β-lactam antibiotics as (aztreonam, piperacillin,piperacillin/tazobactam,ceftazidimeand cefepime), as well as ofloxacinand netilmicin.While the most effective agents were: polymixin B and colistin.In general, most of the tested isolates showed multidrug resistance with seventeendifferent resistance patterns observed.The MICsof 7 selected antibiotics (ceftazidime, cefepime, imipenem, colistin, amikacin, levofloxacin, and piperacillin/tazobactam) against the different clinical isolates was determined by agar dilution technique. The recommendations for MIC breakpoints of the antibiotics are according to the guidelines of the CLSI 2011. Following the initial screening of the prevalence of resistance to different antibiotics, the effect of combining selected antibiotics with colistin was investigated. The antibiotics used were amikacin, imipenem, levofloxacin and cefepime. Combinations of colistin with each of the four antimicrobial agents at different concentrations of each were studied using the checkerboard technique.Further investigations of the dynamics of two combinations (colistin-amikacin and colistin-imipenem) werestudied at concentration ¼ MIC of each agent using the viable count technique.The combination of colistin with each of imipenem, amikacin, or levofloxacin produced synergistic effect with most of the resistant isolates. Also indifference effect appeared in some of the isolates.
Summary 105P. aeruginosais characterized by its intrinsic multidrug resistance to multiple antimicrobial agents. This intrinsic resistance owes much to number of multidrug efflux systems which can extrude variable structurally unrelated compounds. The main efflux pumps present in P. aeruginosabelong to the RND superfamily, among which MexAB-OprM and MexXY-OprM.Our study examinedthe effect of efflux pumps overexpression on development of resistance in MDRPA strains using the quantitative RT-PCR technique.Two-to 786 folds increaseinthe expression of the mexAgeneand 2-2385 folds increaseinthe expression of the mexXgene were observe