<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03767283</url>
  </required_header>
  <id_info>
    <org_study_id>HAA</org_study_id>
    <nct_id>NCT03767283</nct_id>
  </id_info>
  <brief_title>Carbapenem and Quinolone Resistance in Klebsiella Pneumoniae</brief_title>
  <official_title>Genetic Characterization of Plasmids Carrying Carbapenemases and Quinolone Resistance Determinants in Klebsiella Pneumoniae Isolates in Assiut University Hospitals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Klebsiella pneumoniae is an important pathogen that frequently causes nosocomial&#xD;
      community-acquired and infections, including pneumonia, urinary tract infections, bloodstream&#xD;
      infections, pyogenic liver abscesses, and septic shock.&#xD;
&#xD;
      An emerging co-existence of carbapenems and fluoroquinolone resistance in Klebsiella&#xD;
      pneumoniae is causing major difficulty in treating infections caused by such pathogen&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Plasmid mediated carbapenem resistance is mainly due to production of carbapenemase which&#xD;
      belong to three classes of β-lactamases, the Ambler class A, B and D β -lactamases, among&#xD;
      which the New Delhi metallo-β -lactamase has attracted significant attention in the last five&#xD;
      years. New Delhi metallo-β -lactamase-1 is a class B metallo-β-lactamase and was first&#xD;
      identified from a Klebsiella pneumoniae strain in 2008.&#xD;
&#xD;
      New Delhi metallo-β -lactamase-1 is frequently associated with other resistance genes, such&#xD;
      as extended spectrum β- lactamase genes and plasmid-mediated quinolone resistance genes,&#xD;
      which allows bacteria to gain resistance to different classes of antimicrobial agents&#xD;
      simultaneously.&#xD;
&#xD;
      Plasmids and Integrons are mobile genetic elements that carry antimicrobial resistance genes.&#xD;
      Horizontal transfer of those mobile genetic elements has been considered as one of the most&#xD;
      important mechanisms for the dissemination of multi-drug resistance among bacteria.&#xD;
&#xD;
      Classification of plasmids on the basis of molecular typing and phylogenetic relatedness may&#xD;
      help understand the distribution of plasmid types, the relationships involving plasmids&#xD;
      carrying antimicrobial resistance genes. Plasmids can be classified into incompatibility&#xD;
      groups by replicon typing or into types (clusters) by restriction fragment length&#xD;
      polymorphism analysis.&#xD;
&#xD;
      Integrons act as genetic platform, which allow capture and expression of antibiotic&#xD;
      resistance genes. There are 3 classes of integrons that are responsible for multi-drug&#xD;
      resistance, which are classified based on the sequence of the integrase gene. Class 1&#xD;
      integrons are the most widespread class in Gram-negative bacteria.&#xD;
&#xD;
      One approach to preventing multi drug resistant infections is combination of two or more&#xD;
      antimicrobial drugs during a treatment regimen . The combination of imipenem plus&#xD;
      ciprofloxacin had shown Synergistic effect .&#xD;
&#xD;
      Loading of antibacterial agents into nanoparticles is one of the most promising approaches to&#xD;
      reduce anti-microbial resistance. Nano formulations could enhance the intracellular&#xD;
      bioavailability of the antimicrobial drugs, and, thus, decreasing the development of&#xD;
      resistance. Moreover, the potential antibacterial activity of some nanoparticle-forming&#xD;
      polymers might further increase the potency of the antibacterial drugs .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 5, 2019</start_date>
  <completion_date type="Anticipated">December 7, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 10, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>effect of combined antibiotic therapy on resistance</measure>
    <time_frame>1 year</time_frame>
    <description>determination of minimum inhibitory concentration to antibiotics before and after combination</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Antibiotic Resistant Strain</condition>
  <eligibility>
    <study_pop>
      <textblock>
        patients with infections admitted to ICUs&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  admitted to intensive care unite&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  healthy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ismail Mohamed, proffesor</last_name>
    <phone>+01003412279</phone>
    <email>ismailsoliman37@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sherine Ahmed, professor</last_name>
    <phone>+01097018789</phone>
    <email>s-aly71@windowslive.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Assiut University</name>
      <address>
        <city>Assiut</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heba A Ahmed</last_name>
      <phone>01090471151</phone>
      <email>Heba3030ali@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Al-Marzooq F, Mohd Yusof MY, Tay ST. Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae. PLoS One. 2015 Jul 23;10(7):e0133654. doi: 10.1371/journal.pone.0133654. eCollection 2015.</citation>
    <PMID>26203651</PMID>
  </reference>
  <reference>
    <citation>Chang CY, Lin HJ, Chang LL, Ma L, Siu LK, Tung YC, Lu PL. Characterization of Extended-Spectrum beta-Lactamase-Carrying Plasmids in Clinical Isolates of Klebsiella pneumoniae from Taiwan. Microb Drug Resist. 2017 Jan;23(1):98-106. doi: 10.1089/mdr.2015.0212. Epub 2016 May 5.</citation>
    <PMID>27148814</PMID>
  </reference>
  <reference>
    <citation>Worthington RJ, Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol. 2013 Mar;31(3):177-84. doi: 10.1016/j.tibtech.2012.12.006. Epub 2013 Jan 18.</citation>
    <PMID>23333434</PMID>
  </reference>
  <reference>
    <citation>Zhao JY, Zhu YQ, Li YN, Mu XD, You LP, Xu C, Qin P, Ma JL. Coexistence of SFO-1 and NDM-1 beta-lactamase genes and fosfomycin resistance gene fosA3 in an Escherichia coli clinical isolate. FEMS Microbiol Lett. 2015 Jan;362(1):1-7. doi: 10.1093/femsle/fnu018. Epub 2014 Dec 4.</citation>
    <PMID>25790496</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Heba Ali Ahmed</investigator_full_name>
    <investigator_title>principle investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03767283
org study id: HAA
nct id: NCT03767283
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
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 .
observational model: Other
time perspective: Prospective
measure: effect of combined antibiotic therapy on resistance
time frame: 1 year
description: determination of minimum inhibitory concentration to antibiotics before and after combination
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Years
maximum age: 50 Years
healthy volunteers: No
last name: Ismail Mohamed, proffesor
phone: +01003412279
email: ismailsoliman37@yahoo.com
last name: Sherine Ahmed, professor
phone: +01097018789
email: s-aly71@windowslive.com
facility: 
status: Recruiting
contact: 
country: Egypt
citation: Al-Marzooq F, Mohd Yusof MY, Tay ST. Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae. PLoS One. 2015 Jul 23;10(7):e0133654. doi: 10.1371/journal.pone.0133654. eCollection 2015.
PMID: 26203651
citation: Chang CY, Lin HJ, Chang LL, Ma L, Siu LK, Tung YC, Lu PL. Characterization of Extended-Spectrum beta-Lactamase-Carrying Plasmids in Clinical Isolates of Klebsiella pneumoniae from Taiwan. Microb Drug Resist. 2017 Jan;23(1):98-106. doi: 10.1089/mdr.2015.0212. Epub 2016 May 5.
PMID: 27148814
citation: Worthington RJ, Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol. 2013 Mar;31(3):177-84. doi: 10.1016/j.tibtech.2012.12.006. Epub 2013 Jan 18.
PMID: 23333434
citation: Zhao JY, Zhu YQ, Li YN, Mu XD, You LP, Xu C, Qin P, Ma JL. Coexistence of SFO-1 and NDM-1 beta-lactamase genes and fosfomycin resistance gene fosA3 in an Escherichia coli clinical isolate. FEMS Microbiol Lett. 2015 Jan;362(1):1-7. doi: 10.1093/femsle/fnu018. Epub 2014 Dec 4.
PMID: 25790496
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Heba Ali Ahmed
investigator title: principle investigator
mesh term: Pneumonia