<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/NCT03250104</url>
  </required_header>
  <id_info>
    <org_study_id>TTU HAARBI 8.810</org_study_id>
    <nct_id>NCT03250104</nct_id>
  </id_info>
  <brief_title>Antibiotic Stewardship and Infection Control in Patients at High Risk of Developing Infection by Clostridium Difficile, Vancomycin-Resistant Enterococci or Multi-Resistant Gram-Negatives</brief_title>
  <acronym>ABSOLUTE</acronym>
  <official_title>Antibiotic Stewardship and Infection Control in Patients at High Risk of Developing Infection by Clostridium Difficile, Vancomycin-Resistant Enterococci or Multi-Resistant Gram-Negatives</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital of Cologne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Freiburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Lübeck</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital of Cologne</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Throughout project, the investigators design, evaluate and disseminate infection control and&#xD;
      antibiotic stewardship (ABS) measures aimed at reducing the incidence of Clostridium&#xD;
      difficile infection (CDI). The measures will focus on known departments with high incidence&#xD;
      of CDI, i.e. a) hematology/oncology, b) other departments/wards demonstrating above-average&#xD;
      infection rates, which were identified throughout previous studies. The infection control&#xD;
      package will include staff training, hand hygiene programs and disinfection measures.&#xD;
      Throughout the ABS package, investigators will develop and implement ABS measures&#xD;
      specifically designed for patients at the highest risk of developing hospital-acquired&#xD;
      infections, i.e. those treated on hematological/oncological wards. Potentially useful ABS&#xD;
      actions even in critically ill patients are early reduction of exposure based on&#xD;
      microbiological results, timely cessation of anti-infective treatment, thoughtful&#xD;
      implementation of screening measures and biomarkers, defined approaches to patients known to&#xD;
      be allergic to penicillins, and vigorous enforcement of clinical and microbiological&#xD;
      diagnosis of infection focus.&#xD;
&#xD;
      The IC and ABS measures aim at educating and assisting clinical personnel in realizing&#xD;
      treatments according to official guidelines. There will not be a direct contact between study&#xD;
      personnel and patient. There will be no direct recruitment of patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, a distinct group of healthcare-associated pathogens (HPs) has become highly&#xD;
      prevalent among hospital inpatients worldwide. Clostridium difficile, vancomycin-resistant&#xD;
      enterococci (VRE), and multi-resistant gram-negative bacteria (MRGN) today are an immediate&#xD;
      threat to hospitalized patients in Western countries, given inferior outcomes and prolonged&#xD;
      treatment associated with such infections.&#xD;
&#xD;
      There are two key clinical strategies to prevent transmission and reduce the overall&#xD;
      incidence of infections by Clostridium difficile and other gut-derived HPs. Infection control&#xD;
      (IC) measures act by avoiding in-hospital transmissions using various interventions,&#xD;
      including hand hygiene, contact isolation and environmental cleaning/disinfection. Antibiotic&#xD;
      stewardship (ABS) on the other hand aims at reducing selective pressure by ascertaining&#xD;
      adequacy of treatment duration, dose, and selection of antibiotics.However, there is a&#xD;
      scarcity of studies showing effectiveness of these strategies in actually reducing nosocomial&#xD;
      infection by HPs. Single room contact isolation has deleterious implications, i.e. increased&#xD;
      cost, decreased patient contacts and quality of life, but has not been proven effective for&#xD;
      most HPs. Current ABS concepts are usually not aimed at the patients with the highest&#xD;
      antibiotic consumption and the highest risk of contracting nosocomial infection by HPs, e.g.&#xD;
      patients with neutropenia following chemotherapy.&#xD;
&#xD;
      ABSOLUTE is a comprehensive clinical study programme assessing IC/ABS measures to reduce&#xD;
      Clostridium difficile infections (CDI) on high-incidence HP/CDI wards in a stepped-wedge&#xD;
      cluster-randomized trial. The study will focus on known departments with high incidence of&#xD;
      CDI, i.e. a) hematology/oncology, b) other departments/wards demonstrating above-average&#xD;
      infection rates, which will be identified throughout previous study by the German Center for&#xD;
      Infection Research (DZIF). This design was chosen as high-risk groups allow optimal resource&#xD;
      utilization by expedited observation of target outcomes and because there is a translational&#xD;
      gap towards implementing established strategies of infection control and ABS in critically&#xD;
      ill patient groups.&#xD;
&#xD;
      Each partner site will identify eight observation wards. To allow measurement of secondary&#xD;
      endpoints relevant to the IC/ABS bundle, especially safety, at least three of the sites&#xD;
      should include their hematology/oncology department into the analysis. The other&#xD;
      wards/departments will be selected based on CDI epidemiology. Incidence of CDI on candidate&#xD;
      study wards/departments should exceed the 75 percentile based on R-Net (DZIF study) data&#xD;
      collected during the preparation phase. The study coordinators will make the ultimate&#xD;
      decision on the participating wards based on discussion with the local team of investigators.&#xD;
      Besides the above-mentioned entry criteria, knowledge of current practices and&#xD;
      approachability of the ward and the related staff may be regarded during the discussion. In&#xD;
      total, each site will perform the analysis on at least ten wards of at least three&#xD;
      departments.&#xD;
&#xD;
      Infection control measures for Clostridium difficile are well established and can be easily&#xD;
      applied into hospital routine. This work package can therefore start ahead of the ABS bundle&#xD;
      with measures aimed at reducing transmission of Clostridium difficile. The infection control&#xD;
      bundle will include staff training, hand hygiene programs, disinfection measures, and contact&#xD;
      isolation. Physicians will be discouraged to prescribe proton pump inhibitors (PPIs) where&#xD;
      not explicitly needed. The bundle will be defined based on current literature. During the&#xD;
      preparation phase of the study, investigators and other personnel from each site will receive&#xD;
      central training courses in infection control measures targeted at reduction of effective&#xD;
      Clostridium difficile transmission. It will be their task to train local staff (ward&#xD;
      physicians, nurses) for compliance with the infection control bundle. For implementation, the&#xD;
      investigator will adapt the bundle to specific local needs, discuss with the responsible&#xD;
      department heads and ward staff, perform training and disseminate standards of care. The&#xD;
      following indicators of process quality will be measured be the investigator in collaboration&#xD;
      with the local hygiene staff: compliance observations (contact isolation, hand hygiene),&#xD;
      education assessment (surveys), and PPI consumption.&#xD;
&#xD;
      Throughout the ABS work package, the investigators will develop and implement an ABS bundle&#xD;
      specifically designed for patients at the highest risk of developing hospital-acquired&#xD;
      infections, i.e. those treated on hematological/oncological wards. Potentially useful ABS&#xD;
      measures even in critically ill patients are early reduction of exposure based on&#xD;
      microbiological results, timely cessation of anti-infective treatment, thoughtful&#xD;
      implementation of screening measures and biomarkers, defined approaches to patients known to&#xD;
      be allergic to penicillins, and vigorous enforcement of clinical and microbiological&#xD;
      diagnosis of infection focus. The study hypothesis is, that the consumption of glycopeptides,&#xD;
      carbapenems, daptomycin, tigecycline, and linezolid can be significantly reduced without&#xD;
      jeopardizing patient outcomes. Reduction of these antibiotics will save last resort&#xD;
      antimicrobials for documented breakthrough infections, reduce colonization and blood stream&#xD;
      infections (BSI) with VRE and extended-spectrum beta-lactamase-producing gram-negatives&#xD;
      (ESBL), and reduce the incidence of CDI.&#xD;
&#xD;
      As a first step, the investigators will guide a consensus process to develop specific ABS&#xD;
      guidelines for hematology/oncology wards. They will develop this guideline primarily as&#xD;
      German S2k (consensus) guideline, but will also seek publication in an international&#xD;
      peer-reviewed journal. For the consensus process, relevant German medical societies and&#xD;
      groups will be invited to send delegates. External experts will be invited to participate in&#xD;
      the process and comment on the guideline as needed. The consensus process will consist of a&#xD;
      kick-off face-to-face meeting with discussion and distribution of work packages, monthly&#xD;
      telephone conferences and finally, a consensus meeting. The guidelines will contain advice on&#xD;
      specific strategies to avoid excessive or wrong usage of anti-infectives and also on quality&#xD;
      indicators of appropriate antibiotic use.&#xD;
&#xD;
      All study sites will receive comprehensive training in the defined ABS criteria as part of a&#xD;
      3-day course program. In addition, sites without established ABS groups or trained ABS&#xD;
      experts will receive standard three-week training by the ABS Initiative&#xD;
      (www.antibiotic-stewardship.de). Afterwards, implementation of the ABS measures will start.&#xD;
      Antibiotic stewards will develop local standards of procedure based on the provided training&#xD;
      and guidelines. They will then train the responsible staff and disseminate guidelines as best&#xD;
      suited for the local work environment, e.g. as pocket cards, posters, or electronically.&#xD;
      Point-prevalence investigations will assure adherence to guidelines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>CDI incidence</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Significant reduction of the overall CDI incidence on intervention wards following implementation of the combined IC and ABS bundles in pre-post analysis stratified by center.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of IC bundle through incidence of CDI or BSI by VRE and MRGN</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Effectiveness of the infection control bundle for preventing nosocomial infection by incidence of a) CDI, or BSI by b) VRE, and c) MRGN by pre-post analysis before implementation of the ABS bundle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PPI usage</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Reduction in the consumption of PPIs, measured by Defined Daily Dose (DDD) before and after IC bundle implementation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of process indicators by calculating disinfectant consumption and antibiotic consumption</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Improvement of process indicators for the IC (disinfectant consumption) and ABS (antibiotic consumption) bundles by pre-post analysis before implementation of the measures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of ABS interventions by continuously measuring RDDs</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Effectiveness of ABS interventions in reducing consumption of antibiotics discouraged for empirical treatment (3rd generation cephalosporins, glycopeptides, carbapenems, daptomycin, tigecycline, and linezolid), measured by Recommended Daily Dose (RDDs) before and after ABS bundle implementation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic consumption</measure>
    <time_frame>Baseline and every 3 months up to 144 weeks</time_frame>
    <description>Time series analysis using monthly aggregations of antibiotic consumption (RDDs) and incidence of a) CDI, b) VRE, and c) MRGN on participating wards and correlation with IC and ABS intervention activities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness by comparing expenditures of implementing IC/ABS measures with reduction in antibiotic consumption</measure>
    <time_frame>Baseline and after 144 weeks (end of the study)</time_frame>
    <description>Cost-effectiveness of the different bundles by reducing antibiotic consumption, abbreviating average inpatient stays, and reducing the need for intensive care treatment compared to expenditure for IC and ABS bundle implementation</description>
  </secondary_outcome>
  <enrollment type="Actual">80000</enrollment>
  <condition>Clostridium Difficile Infection</condition>
  <condition>VRE Infection</condition>
  <condition>Nosocomial Infection</condition>
  <condition>MRGN Bacteria</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Infection Control</intervention_name>
    <description>The infection control bundle will include staff training, hand hygiene programs, disinfection measures, and contact isolation. Physicians will be discouraged to prescribe proton pump inhibitors (PPIs) where not explicitly needed. The intervention bundle will be defined based on current literature. For implementation, the investigator will adapt the bundle to specific local needs, discuss with the responsible department heads and ward staff, perform training and disseminate standards of care.</description>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Antibiotic Stewardship</intervention_name>
    <description>Antibiotic stewards will develop local standards of procedure based on the provided training and guidelines. They will then train the responsible staff and disseminate guidelines as best suited for the local work environment, e.g. as pocket cards, posters, or electronically. Point-prevalence investigations and &quot;antibiotic visits&quot; will assure adherence to guidelines.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted on wards with high incidence of CDI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - patients admitted to departments with high incidence of CDI, i.e. a) hematology/oncology,&#xD;
        b) other departments/wards demonstrating above-average infection rates (identified by&#xD;
        previous studies)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - patients admitted in opthalmology, paediatrics, psychiatry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jörg Janne Vehreschild, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Cologne</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Cologne</name>
      <address>
        <city>Cologne</city>
        <state>NRW</state>
        <zip>50931</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Gastmeier P, Weitzel-Kage D, Behnke M, Eckmanns T. Surveillance of Clostridium difficile-associated diarrhoea with the German nosocomial infection surveillance system KISS (CDAD-KISS). Int J Antimicrob Agents. 2009 Mar;33 Suppl 1:S19-23. doi: 10.1016/S0924-8579(09)70011-1.</citation>
    <PMID>19303563</PMID>
  </reference>
  <reference>
    <citation>Meyer E, Gastmeier P, Weizel-Kage D, Schwab F. Associations between nosocomial meticillin-resistant Staphylococcus aureus and nosocomial Clostridium difficile-associated diarrhoea in 89 German hospitals. J Hosp Infect. 2012 Nov;82(3):181-6. doi: 10.1016/j.jhin.2012.07.022. Epub 2012 Sep 27.</citation>
    <PMID>23021304</PMID>
  </reference>
  <reference>
    <citation>Vonberg RP, Kuijper EJ, Wilcox MH, Barbut F, Tull P, Gastmeier P; European C difficile-Infection Control Group; European Centre for Disease Prevention and Control (ECDC); van den Broek PJ, Colville A, Coignard B, Daha T, Debast S, Duerden BI, van den Hof S, van der Kooi T, Maarleveld HJ, Nagy E, Notermans DW, O'Driscoll J, Patel B, Stone S, Wiuff C. Infection control measures to limit the spread of Clostridium difficile. Clin Microbiol Infect. 2008 May;14 Suppl 5:2-20. doi: 10.1111/j.1469-0691.2008.01992.x.</citation>
    <PMID>18412710</PMID>
  </reference>
  <reference>
    <citation>Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Hantschel M, Peter S, Schafhausen P, Rohde H, Lilienfeld-Toal MV, Bekeredjian-Ding I, Libam J, Hellmich M, Vehreschild JJ, Cornely OA, Seifert H. A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother. 2014 Dec;69(12):3387-92. doi: 10.1093/jac/dku305. Epub 2014 Aug 6.</citation>
    <PMID>25103492</PMID>
  </reference>
  <reference>
    <citation>Vehreschild MJ, Weitershagen D, Biehl LM, Tacke D, Waldschmidt D, Tox U, Wisplinghoff H, Von Bergwelt-Baildon M, Cornely OA, Vehreschild JJ. Clostridium difficile infection in patients with acute myelogenous leukemia and in patients undergoing allogeneic stem cell transplantation: epidemiology and risk factor analysis. Biol Blood Marrow Transplant. 2014 Jun;20(6):823-8. doi: 10.1016/j.bbmt.2014.02.022. Epub 2014 Mar 6.</citation>
    <PMID>24607558</PMID>
  </reference>
  <reference>
    <citation>Borde JP, Litterst S, Ruhnke M, Feik R, Hubner J, deWith K, Kaier K, Kern WV. Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany. Infection. 2015 Feb;43(1):45-50. doi: 10.1007/s15010-014-0693-2. Epub 2014 Oct 25.</citation>
    <PMID>25344419</PMID>
  </reference>
  <reference>
    <citation>Borde JP, Kaier K, Steib-Bauert M, Vach W, Geibel-Zehender A, Busch H, Bertz H, Hug M, de With K, Kern WV. Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center. BMC Infect Dis. 2014 Apr 15;14:201. doi: 10.1186/1471-2334-14-201.</citation>
    <PMID>24731220</PMID>
  </reference>
  <reference>
    <citation>Vehreschild JJ, Bohme A, Cornely OA, Kahl C, Karthaus M, Kreuzer KA, Maschmeyer G, Mousset S, Ossendorf V, Penack O, Vehreschild MJGT, Bohlius J. Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO). Ann Oncol. 2014 Sep;25(9):1709-1718. doi: 10.1093/annonc/mdu035. Epub 2014 Mar 14.</citation>
    <PMID>24631945</PMID>
  </reference>
  <reference>
    <citation>Vehreschild JJ, Morgen G, Cornely OA, Hartmann P, Koch S, Kalka-Moll W, Wyen C, Vehreschild MJ, Lehmann C, Gillor D, Seifert H, Kremer G, Fatkenheuer G, Jung N. Evaluation of an infectious disease consultation programme in a German tertiary care hospital. Infection. 2013 Dec;41(6):1121-8. doi: 10.1007/s15010-013-0512-1. Epub 2013 Aug 8.</citation>
    <PMID>23925637</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital of Cologne</investigator_affiliation>
    <investigator_full_name>Dr. med. Jörg Janne Vehreschild</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>antimicrobial stewardship</keyword>
  <keyword>infection control</keyword>
  <keyword>nosocomial infection</keyword>
  <keyword>clostridium difficile</keyword>
  <keyword>MRGN bacteria</keyword>
  <keyword>health-care associated pathogens</keyword>
  <keyword>VRE</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Cross Infection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be shared after the end of the study</ipd_description>
  </patient_data>
  <!-- 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/NCT03250104
org study id: TTU HAARBI 8.810
nct id: NCT03250104
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Throughout project, the investigators design, evaluate and disseminate infection control and
      antibiotic stewardship (ABS) measures aimed at reducing the incidence of Clostridium
      difficile infection (CDI). The measures will focus on known departments with high incidence
      of CDI, i.e. a) hematology/oncology, b) other departments/wards demonstrating above-average
      infection rates, which were identified throughout previous studies. The infection control
      package will include staff training, hand hygiene programs and disinfection measures.
      Throughout the ABS package, investigators will develop and implement ABS measures
      specifically designed for patients at the highest risk of developing hospital-acquired
      infections, i.e. those treated on hematological/oncological wards. Potentially useful ABS
      actions even in critically ill patients are early reduction of exposure based on
      microbiological results, timely cessation of anti-infective treatment, thoughtful
      implementation of screening measures and biomarkers, defined approaches to patients known to
      be allergic to penicillins, and vigorous enforcement of clinical and microbiological
      diagnosis of infection focus.

      The IC and ABS measures aim at educating and assisting clinical personnel in realizing
      treatments according to official guidelines. There will not be a direct contact between study
      personnel and patient. There will be no direct recruitment of patients.
In recent years, a distinct group of healthcare-associated pathogens (HPs) has become highly
      prevalent among hospital inpatients worldwide. Clostridium difficile, vancomycin-resistant
      enterococci (VRE), and multi-resistant gram-negative bacteria (MRGN) today are an immediate
      threat to hospitalized patients in Western countries, given inferior outcomes and prolonged
      treatment associated with such infections.

      There are two key clinical strategies to prevent transmission and reduce the overall
      incidence of infections by Clostridium difficile and other gut-derived HPs. Infection control
      (IC) measures act by avoiding in-hospital transmissions using various interventions,
      including hand hygiene, contact isolation and environmental cleaning/disinfection. Antibiotic
      stewardship (ABS) on the other hand aims at reducing selective pressure by ascertaining
      adequacy of treatment duration, dose, and selection of antibiotics.However, there is a
      scarcity of studies showing effectiveness of these strategies in actually reducing nosocomial
      infection by HPs. Single room contact isolation has deleterious implications, i.e. increased
      cost, decreased patient contacts and quality of life, but has not been proven effective for
      most HPs. Current ABS concepts are usually not aimed at the patients with the highest
      antibiotic consumption and the highest risk of contracting nosocomial infection by HPs, e.g.
      patients with neutropenia following chemotherapy.

      ABSOLUTE is a comprehensive clinical study programme assessing IC/ABS measures to reduce
      Clostridium difficile infections (CDI) on high-incidence HP/CDI wards in a stepped-wedge
      cluster-randomized trial. The study will focus on known departments with high incidence of
      CDI, i.e. a) hematology/oncology, b) other departments/wards demonstrating above-average
      infection rates, which will be identified throughout previous study by the German Center for
      Infection Research (DZIF). This design was chosen as high-risk groups allow optimal resource
      utilization by expedited observation of target outcomes and because there is a translational
      gap towards implementing established strategies of infection control and ABS in critically
      ill patient groups.

      Each partner site will identify eight observation wards. To allow measurement of secondary
      endpoints relevant to the IC/ABS bundle, especially safety, at least three of the sites
      should include their hematology/oncology department into the analysis. The other
      wards/departments will be selected based on CDI epidemiology. Incidence of CDI on candidate
      study wards/departments should exceed the 75 percentile based on R-Net (DZIF study) data
      collected during the preparation phase. The study coordinators will make the ultimate
      decision on the participating wards based on discussion with the local team of investigators.
      Besides the above-mentioned entry criteria, knowledge of current practices and
      approachability of the ward and the related staff may be regarded during the discussion. In
      total, each site will perform the analysis on at least ten wards of at least three
      departments.

      Infection control measures for Clostridium difficile are well established and can be easily
      applied into hospital routine. This work package can therefore start ahead of the ABS bundle
      with measures aimed at reducing transmission of Clostridium difficile. The infection control
      bundle will include staff training, hand hygiene programs, disinfection measures, and contact
      isolation. Physicians will be discouraged to prescribe proton pump inhibitors (PPIs) where
      not explicitly needed. The bundle will be defined based on current literature. During the
      preparation phase of the study, investigators and other personnel from each site will receive
      central training courses in infection control measures targeted at reduction of effective
      Clostridium difficile transmission. It will be their task to train local staff (ward
      physicians, nurses) for compliance with the infection control bundle. For implementation, the
      investigator will adapt the bundle to specific local needs, discuss with the responsible
      department heads and ward staff, perform training and disseminate standards of care. The
      following indicators of process quality will be measured be the investigator in collaboration
      with the local hygiene staff: compliance observations (contact isolation, hand hygiene),
      education assessment (surveys), and PPI consumption.

      Throughout the ABS work package, the investigators will develop and implement an ABS bundle
      specifically designed for patients at the highest risk of developing hospital-acquired
      infections, i.e. those treated on hematological/oncological wards. Potentially useful ABS
      measures even in critically ill patients are early reduction of exposure based on
      microbiological results, timely cessation of anti-infective treatment, thoughtful
      implementation of screening measures and biomarkers, defined approaches to patients known to
      be allergic to penicillins, and vigorous enforcement of clinical and microbiological
      diagnosis of infection focus. The study hypothesis is, that the consumption of glycopeptides,
      carbapenems, daptomycin, tigecycline, and linezolid can be significantly reduced without
      jeopardizing patient outcomes. Reduction of these antibiotics will save last resort
      antimicrobials for documented breakthrough infections, reduce colonization and blood stream
      infections (BSI) with VRE and extended-spectrum beta-lactamase-producing gram-negatives
      (ESBL), and reduce the incidence of CDI.

      As a first step, the investigators will guide a consensus process to develop specific ABS
      guidelines for hematology/oncology wards. They will develop this guideline primarily as
      German S2k (consensus) guideline, but will also seek publication in an international
      peer-reviewed journal. For the consensus process, relevant German medical societies and
      groups will be invited to send delegates. External experts will be invited to participate in
      the process and comment on the guideline as needed. The consensus process will consist of a
      kick-off face-to-face meeting with discussion and distribution of work packages, monthly
      telephone conferences and finally, a consensus meeting. The guidelines will contain advice on
      specific strategies to avoid excessive or wrong usage of anti-infectives and also on quality
      indicators of appropriate antibiotic use.

      All study sites will receive comprehensive training in the defined ABS criteria as part of a
      3-day course program. In addition, sites without established ABS groups or trained ABS
      experts will receive standard three-week training by the ABS Initiative
      (www.antibiotic-stewardship.de). Afterwards, implementation of the ABS measures will start.
      Antibiotic stewards will develop local standards of procedure based on the provided training
      and guidelines. They will then train the responsible staff and disseminate guidelines as best
      suited for the local work environment, e.g. as pocket cards, posters, or electronically.
      Point-prevalence investigations will assure adherence to guidelines.
observational model: Cohort
time perspective: Prospective
measure: CDI incidence
time frame: Baseline and every 3 months up to 144 weeks
description: Significant reduction of the overall CDI incidence on intervention wards following implementation of the combined IC and ABS bundles in pre-post analysis stratified by center.
measure: Effectiveness of IC bundle through incidence of CDI or BSI by VRE and MRGN
time frame: Baseline and every 3 months up to 144 weeks
description: Effectiveness of the infection control bundle for preventing nosocomial infection by incidence of a) CDI, or BSI by b) VRE, and c) MRGN by pre-post analysis before implementation of the ABS bundle.
measure: PPI usage
time frame: Baseline and every 3 months up to 144 weeks
description: Reduction in the consumption of PPIs, measured by Defined Daily Dose (DDD) before and after IC bundle implementation
measure: Improvement of process indicators by calculating disinfectant consumption and antibiotic consumption
time frame: Baseline and every 3 months up to 144 weeks
description: Improvement of process indicators for the IC (disinfectant consumption) and ABS (antibiotic consumption) bundles by pre-post analysis before implementation of the measures
measure: Effectiveness of ABS interventions by continuously measuring RDDs
time frame: Baseline and every 3 months up to 144 weeks
description: Effectiveness of ABS interventions in reducing consumption of antibiotics discouraged for empirical treatment (3rd generation cephalosporins, glycopeptides, carbapenems, daptomycin, tigecycline, and linezolid), measured by Recommended Daily Dose (RDDs) before and after ABS bundle implementation
measure: Antibiotic consumption
time frame: Baseline and every 3 months up to 144 weeks
description: Time series analysis using monthly aggregations of antibiotic consumption (RDDs) and incidence of a) CDI, b) VRE, and c) MRGN on participating wards and correlation with IC and ABS intervention activities
measure: Cost-effectiveness by comparing expenditures of implementing IC/ABS measures with reduction in antibiotic consumption
time frame: Baseline and after 144 weeks (end of the study)
description: Cost-effectiveness of the different bundles by reducing antibiotic consumption, abbreviating average inpatient stays, and reducing the need for intensive care treatment compared to expenditure for IC and ABS bundle implementation
intervention type: Other
intervention name: Infection Control
description: The infection control bundle will include staff training, hand hygiene programs, disinfection measures, and contact isolation. Physicians will be discouraged to prescribe proton pump inhibitors (PPIs) where not explicitly needed. The intervention bundle will be defined based on current literature. For implementation, the investigator will adapt the bundle to specific local needs, discuss with the responsible department heads and ward staff, perform training and disseminate standards of care.
intervention type: Other
intervention name: Antibiotic Stewardship
description: Antibiotic stewards will develop local standards of procedure based on the provided training and guidelines. They will then train the responsible staff and disseminate guidelines as best suited for the local work environment, e.g. as pocket cards, posters, or electronically. Point-prevalence investigations and "antibiotic visits" will assure adherence to guidelines.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jörg Janne Vehreschild, MD
role: Principal Investigator
affiliation: University Hospital Cologne
facility: 
country: Germany
citation: Gastmeier P, Weitzel-Kage D, Behnke M, Eckmanns T. Surveillance of Clostridium difficile-associated diarrhoea with the German nosocomial infection surveillance system KISS (CDAD-KISS). Int J Antimicrob Agents. 2009 Mar;33 Suppl 1:S19-23. doi: 10.1016/S0924-8579(09)70011-1.
PMID: 19303563
citation: Meyer E, Gastmeier P, Weizel-Kage D, Schwab F. Associations between nosocomial meticillin-resistant Staphylococcus aureus and nosocomial Clostridium difficile-associated diarrhoea in 89 German hospitals. J Hosp Infect. 2012 Nov;82(3):181-6. doi: 10.1016/j.jhin.2012.07.022. Epub 2012 Sep 27.
PMID: 23021304
citation: Vonberg RP, Kuijper EJ, Wilcox MH, Barbut F, Tull P, Gastmeier P; European C difficile-Infection Control Group; European Centre for Disease Prevention and Control (ECDC); van den Broek PJ, Colville A, Coignard B, Daha T, Debast S, Duerden BI, van den Hof S, van der Kooi T, Maarleveld HJ, Nagy E, Notermans DW, O'Driscoll J, Patel B, Stone S, Wiuff C. Infection control measures to limit the spread of Clostridium difficile. Clin Microbiol Infect. 2008 May;14 Suppl 5:2-20. doi: 10.1111/j.1469-0691.2008.01992.x.
PMID: 18412710
citation: Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Hantschel M, Peter S, Schafhausen P, Rohde H, Lilienfeld-Toal MV, Bekeredjian-Ding I, Libam J, Hellmich M, Vehreschild JJ, Cornely OA, Seifert H. A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother. 2014 Dec;69(12):3387-92. doi: 10.1093/jac/dku305. Epub 2014 Aug 6.
PMID: 25103492
citation: Vehreschild MJ, Weitershagen D, Biehl LM, Tacke D, Waldschmidt D, Tox U, Wisplinghoff H, Von Bergwelt-Baildon M, Cornely OA, Vehreschild JJ. Clostridium difficile infection in patients with acute myelogenous leukemia and in patients undergoing allogeneic stem cell transplantation: epidemiology and risk factor analysis. Biol Blood Marrow Transplant. 2014 Jun;20(6):823-8. doi: 10.1016/j.bbmt.2014.02.022. Epub 2014 Mar 6.
PMID: 24607558
citation: Borde JP, Litterst S, Ruhnke M, Feik R, Hubner J, deWith K, Kaier K, Kern WV. Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany. Infection. 2015 Feb;43(1):45-50. doi: 10.1007/s15010-014-0693-2. Epub 2014 Oct 25.
PMID: 25344419
citation: Borde JP, Kaier K, Steib-Bauert M, Vach W, Geibel-Zehender A, Busch H, Bertz H, Hug M, de With K, Kern WV. Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center. BMC Infect Dis. 2014 Apr 15;14:201. doi: 10.1186/1471-2334-14-201.
PMID: 24731220
citation: Vehreschild JJ, Bohme A, Cornely OA, Kahl C, Karthaus M, Kreuzer KA, Maschmeyer G, Mousset S, Ossendorf V, Penack O, Vehreschild MJGT, Bohlius J. Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO). Ann Oncol. 2014 Sep;25(9):1709-1718. doi: 10.1093/annonc/mdu035. Epub 2014 Mar 14.
PMID: 24631945
citation: Vehreschild JJ, Morgen G, Cornely OA, Hartmann P, Koch S, Kalka-Moll W, Wyen C, Vehreschild MJ, Lehmann C, Gillor D, Seifert H, Kremer G, Fatkenheuer G, Jung N. Evaluation of an infectious disease consultation programme in a German tertiary care hospital. Infection. 2013 Dec;41(6):1121-8. doi: 10.1007/s15010-013-0512-1. Epub 2013 Aug 8.
PMID: 23925637
responsible party type: Principal Investigator
investigator affiliation: University Hospital of Cologne
investigator full name: Dr. med. Jörg Janne Vehreschild
investigator title: Professor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Clostridium Infections
mesh term: Cross Infection
mesh term: Anti-Bacterial Agents
sharing ipd: No
ipd description: Individual participant data will not be shared after the end of the study