Carbapenem and Quinolone Resistance in Klebsiella Pneumoniae

Study Overview
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Brief Summary
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Klebsiella pneumoniae is an important pathogen that frequently causes nosocomial community-acquired and infections, including pneumonia, urinary tract infections, bloodstream infections, pyogenic liver abscesses, and septic shock. An emerging co-existence of carbapenems and fluoroquinolone resistance in Klebsiella pneumoniae is causing major difficulty in treating infections caused by such pathogen

Detailed Description
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Plasmid mediated carbapenem resistance is mainly due to production of carbapenemase which belong to three classes of β-lactamases, the Ambler class A, B and D β -lactamases, among which the New Delhi metallo-β -lactamase has attracted significant attention in the last five years. New Delhi metallo-β -lactamase-1 is a class B metallo-β-lactamase and was first identified from a Klebsiella pneumoniae strain in 2008. New Delhi metallo-β -lactamase-1 is frequently associated with other resistance genes, such as extended spectrum β- lactamase genes and plasmid-mediated quinolone resistance genes, which allows bacteria to gain resistance to different classes of antimicrobial agents simultaneously. Plasmids and Integrons are mobile genetic elements that carry antimicrobial resistance genes. Horizontal transfer of those mobile genetic elements has been considered as one of the most important mechanisms for the dissemination of multi-drug resistance among bacteria. Classification of plasmids on the basis of molecular typing and phylogenetic relatedness may help understand the distribution of plasmid types, the relationships involving plasmids carrying antimicrobial resistance genes. Plasmids can be classified into incompatibility groups by replicon typing or into types (clusters) by restriction fragment length polymorphism analysis. Integrons act as genetic platform, which allow capture and expression of antibiotic resistance genes. There are 3 classes of integrons that are responsible for multi-drug resistance, which are classified based on the sequence of the integrase gene. Class 1 integrons are the most widespread class in Gram-negative bacteria. One approach to preventing multi drug resistant infections is combination of two or more antimicrobial drugs during a treatment regimen . The combination of imipenem plus ciprofloxacin had shown Synergistic effect . Loading of antibacterial agents into nanoparticles is one of the most promising approaches to reduce anti-microbial resistance. Nano formulations could enhance the intracellular bioavailability of the antimicrobial drugs, and, thus, decreasing the development of resistance. Moreover, the potential antibacterial activity of some nanoparticle-forming polymers might further increase the potency of the antibacterial drugs .

Official Title
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Genetic Characterization of Plasmids Carrying Carbapenemases and Quinolone Resistance Determinants in Klebsiella Pneumoniae Isolates in Assiut University Hospitals

Conditions
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Antibiotic Resistant Strain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: admitted to intensive care unite Exclusion Criteria: healthy

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of combined antibiotic therapy on resistance | determination of minimum inhibitory concentration to antibiotics before and after combination | 1 year |