الفهرس 
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Abstract
6. SUMMARY
Antibiotic resistance is a key threat facing humanity worldwide and has been declared so by health organizations like the World Health Organization (WHO). Resistance to β-lactam antibiotics has been reported to be a bacterial defense mechanism observed in many bacteria. Appropriate use of antibiotics in a health care setting is important. Inappropriate administration of antibiotics in suboptimal doses and repeated use of a single class of antibiotics for the prolonged or reduced duration of time will also increase the prevalence rate of drug resistance.
According to our study rationale, there is a rising trend in the prevalence of ESBL producing strains. ESBLs are those strains of bacteria that synthesize beta-lactamases that hydrolyses the beta- lactam ring of most of the beta-lactam antibiotics. This mostly includes the broad spectrum cephalosporins. Poor clinical outcome is always associated with the infections caused by these ESBL producers. The problem associated with this is the selection of which antibiotic to test because of the different levels of activity exhibited by various ESBLs against cephalosporins making it difficult for detection.
Therefore, the present study is carried out to detect and characterize ESBL producing Gram-negative Escherichia coli strains isolated from various clinical specimens obtained in the clinical microbiology laboratory, Benha hospitals. Phenotypic ESBL detection was carried out according to updated CLSI guidelines
The results of this study can be abridged as following:
1- A total of 72 clinical samples obtained from Benha general Hospital and, from 2019 to 2020 were included in this study. Sample type includes sputum – 12, urine - 43, and Wounds -17 . These sample have been isolated from 40% male patients and 60% female.
2- Escherichia coli infections are more common in females and contribute to urinary infections than males mostly as a nosocomial pathogen.
3- Age is not a necessarily factor to bacterial infections although elderly individuals above 60 years of age are prone to infection; perhaps due to compromised immune.
4- E. coil isolates tested against different antibiotic discs. The results showed that isolates were sensitive to Amikacin (AK); 30 µg, Piperacillin – Tazobactam (PTZ); 30 µg, and Gentamicin (GN); 5 µg. On the other hand, E. coli showed high resistance rates to Ampicillin (AMP); 15 µg, Cephalexin (CN); 30 µg, Ofloxacin (OFX); 2 µg, Norfloxacin (NXN); 10 µg, Azithromycin (AZM); 15 µg, Aztreonam (AZT); 30 µg; Ciprofloxacin (CIP); 1 µg); Moxifloxacin (MFX); 5 µg, Trimethoprime/ sulfamethoxazole (SXT); 25 µg; and Gemifloxacin (GM); 10 µg.
5- Detection of ESBLs by Antibiotics susceptibility testing which achieved using Kirby- Bauer’s disk diffusion method. E. coli isolates presented highest antibiotic resistance to Aztreonam (AZT); 30 µg 10/10 (100%; p≤0.005) followed by Cefotaxime (5 µg) – 8/10 (80%; p≤0.005), and Ceftazidime (CTZ); (5 µg)- 7/10 (70%; p<0.001 whereas the maximum effective antibiotic (least resistance) was imipenem (10 µg) – 2/10 (20%; p≤0.005) and
Doripenem (30 µg) – 4/10 (40%; p≤0.005).
6- Depending on the pharmacokinetic and pharmacodymanic properties of imipenem, it can be touted to be the only antibiotic that could be helpful in treating infections in the state. However, ceftriazone and combinatorial therapy is a means of antibiotic therapy.
7- ESBLs producers were screened for the genes (β-lactamase gene) with primers for TEM, CTX-M, and SHVgenes. Present study gives a prevalence rate of 100% for CTX-M gene, 90% for TEM. The most common ESBL genotype among our isolates was CTX-M and TEM whereas SHV gene was found to be negative.
8- Identification of most resistant isolates by 16S Rrna. The VITEK 2 system reported (Probability 98.0%) correct organism-antibiotic combinations within ±twofold dilution compared with the manual method.
9- The MICs of the PPE were examined to evaluate their bacteriostatic and bactericidal properties. The aqueous extract against E. coli was found to be 60 mg/L, although the growth of these isolates was inhibited by 100 mg/L of aqueous extract
10- Measurements of Time-kill kinetics by PPE were made for all isolates. PPE showed greater activity against all the isolates of E. coli that were killed within 4 hours.
11- Chief constituents recognized by GC/MS in the extracts of the Pomegranate Peel extract. Twenty-one compounds were detected in the extract like (Geranyl vinyl ether, Linalool, benzoic acid, Benzaldehyde, Oleic Acid, Phenol, 2- methoxy-3 (2-propenyl), and Eicosapentaenoic acid).
12- Gene expression of CTX and TEM were downregulated after isolates treatment with PPE.