Clostridium Difficile Infection Clinical Trial
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
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.
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