الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Rising prevalence of XDR K. pneumoniae strains represent a major threat in Egypt especially for ICU patients and have enormous challenges regarding treatment plans. Consequently, there is an urgent need for innovative therapies for their treatment such as using unconventional antibiotic forms for example nanotechnology and different, unusual, available antibiotic combinations against K. pneumoniae. Niosomes have tremendous advantages as drug carriers. It can affect bioavailability, physical and chemical properties of loaded antibiotic leading to decreasing the resistance pattern. Aim: we sought to formulate a niosomal form of Azithromycin and study its characteristics together with its effect on XDR K. pneumoniae and also test the effect of several combination therapies namely AZM solution/levofloxacin, AZM niosomes/levofloxacin, ceftazidime/gentamicin, cefepime/amoxicillin-clavulanate and meropenem/ampicillin sulbactam combinations against studied strains, aiming to find a treatment option for XDR strains. Material/Methods: Forty XDR K. pneumoniae isolates were included in the study. The MIC test was done for all antibiotics studied in combinations and the colistin MIC was tested to categorize the isolates into colistin sensitive and colistin resistant. The effect of antibiotic combinations was studied using checkerboard test and the results confirmed by time kill assay. Lastly the post antibiotic effect of each antibiotic alone and in combination was assessed. Results: High percentage of the strains (42.5%) were colistin resistant and the MIC of both AZM formulas against K. pneumoniae revealed that AZM niosomes mean MIC was significantly lower than the mean MIC of AZM solution and all tested strains were resistant to all examined antibiotics. AZM niosomes when combined with levofloxacin was more effective with (40%) synergy strains than AZM solution /levofloxacin combination which resulted only in (20%) synergy strains. Ceftazidime/gentamicin combination showed a synergistic effect in (25%) of isolates. The indifference effect aassociated with the last two combinations (cefepime/amoxicillin-clavulanate and meropenem/ampicillin sulbactam). No antagonistic effect was revealed. The checkerboard assay was found to have high sensitivity and specificity when compared to time kill assay. All tested antibiotics showed decrease in their MIC after combination and also showed a significant PAE.