الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
There is no doubt that the past years have brought a tremendous challenge to the clinical arena. Carbapenems, being the most powerful antibiotics, up till now, against Enterobacteriaceae, are becoming increasingly ineffective. Nowadays, the wide spread of CRE is considered as a dangerous problem in many healthcare settings.
The aim of this thesis was to detect the presence of resistance to the carbapenems: imipenem and meropenem among different Enterobacteriaceae clinical isolates in Egypt. Moreover, to emphasize on the molecular distribution of genes conferring resistance to these antibiotics among selected clinical isolates. Finally, to reach the appropriate and effective approach for the treatment of CRE infections using combinations of carbapenems with other drugs.
In this study, 96 Enterobacteriaceae clinical isolates from different specimens were obtained from three governorates in Egypt: Alexandria, Cairo and Al Behaira. Besides, two standard strains (Escherichia coli NCTC 10418 and Klebsiella pneumoniae ATCC 13883) were used. The isolates were identified by classical microscopical and biochemical methods as follows: 50 Klebsiella spp., 39 E. coli and 7 P. vulgaris. from these, eighteen Klebsiella clinical isolates were selected and were used in most of the experiments carried out in this study. These Klebsiella isolates were subjected to further identification using the MALDI-TOF mass spectrometry. Among these eighteen isolates, 12 isolates were identified as Klebsiella pneumoniae. These were: K3, K28, K44, K45, K48, K58, K62, K73, K76, K81, K85 and K89. On the other hand, 6 isolates were identified as Klebsiella variicola: K25, K37, K40, K56, K77 and K92.
All the collected clinical isolates were tested for their susceptibility to 14 different antibiotics using the disc diffusion technique. Out of the ninety-six collected clinical isolates, 48 isolates were resistant to IPM and 70 isolates were resistant to MEM.
The antimicrobial activity of each of IPM and MEM against the collected clinical isolates was investigated through MIC determination using the agar dilution method. Concerning the E. coli clinical isolates, the MIC ranges lied between (0.031- 32 μg/mL) for IPM and (0.031- 256 μg/mL) for MEM. For the Klebsiella clinical isolates, the MIC ranges lied between (0.063- 512 μg/mL) in case of IPM and (0.031- 1024 μg/mL) in case of MEM. Regarding the P. vulgaris clinical isolates, the MIC ranges lied between (2- 16 μg/mL) for IPM and (0.031- 32 μg/mL) for MEM.
As a prerequisite for the checkerboard test and the time-kill assay, the broth dilution method was used to determine the MICs of IPM, MEM, RA, CIP, COL and AK against selected CRE clinical isolates. It was noticed that, in case of both tested carbapenems IPM and MEM, no considerable difference in the obtained MICs was detected between both the agar and broth dilution methods. On the other hand, the ranges of the obtained MICs of RA, CIP, COL and AK against the tested isolates were (8- 2048 μg/mL), (0.125- 1024 μg/mL), (4- 16 μg/mL) and (8- 16384 μg/mL), respectivel