Patients at High Risk of Antibacterial Treatment Upon Admission Clinical Trial
Official title:
Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens
Extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), vancomycin-resistant enterococci (VRE) and Clostridium difficile have become a major threat to hospitalised patients worldwide. We hypothesize that receiving inappropriate antibacterial treatment places patients at high risk of intestinal domination and subsequent infection by these bacteria. Further analyses will address cost-effectiveness of specific interventions, behavioural analyses of the decision process leading to inappropriate antibacterial treatment, and the rate of undetected colonization with EPE/VRE/C. difficile on admission.
The prevalence of antimicrobial resistant pathogens has dramatically increased among
hospitalised patients worldwide. While various management strategies have effectively reduced
the burden caused by methicillin-resistant Staphylococcus aureus, resistant pathogens with a
preference towards intestinal colonization are currently on the rise. E.g.,
vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase producing
Enterobacteriaceae (EPE) now constitute a significant threat to hospitalised patients
worldwide, as infections due to these organisms require prolonged treatments and result in
inferior outcomes. Similarly, the burden of disease caused by Clostridium difficile infection
(CDI), the main cause of healthcare-associated infectious diarrhoea, has increased driven by
the emergence of hypervirulent strains such as ribotypes 027 and 078. Molecular studies have
demonstrated that increased population-wide exposure to broad-spectrum antibacterials is a
crucial step in the initiation of outbreaks by selection and expansion of resistant C.
difficile.
This is a comprehensive, multinational, multi-centre clinical study aiming to assess the
impact of inappropriate antibacterial prescription on intestinal domination by EPE or VRE or
infection with C. difficile. To achieve this goal, the study will closely follow the
progression from first acquisition of drug-resistant organisms to infection with these
bacteria at an individual patient level.
In this study, we will establish the sequence and factors involved in acquisition,
colonization, selective pressure, bacterial overgrowth/domination/ and infection for EPE, VRE
and C. difficile. We hypothesize that IC (Infection Control; prevention of pathogen
acquisition) and AMS (Antimicrobial Stewardship; prevention of clonal expansion) measures
leading to a higher share of appropriate anti-infective use are effective strategies to
prevent this development. The study programme will allow an accurate estimation of the
preventable share of healthcare-acquired colonization and infection by VRE, EPE, and C.
difficile.
No direct interventions will be performed with study patients. Instead, study centres will
assess quality indicators for implementation of IC and AMS measures by active observation and
aggregation of data. Patients fulfilling all inclusion- and no exclusion criteria will be
asked for their consent to be recruited prospectively into a cohort study. During the
observational phase, participants will be monitored for receipt of antibacterial treatment
and regular stool samples will be obtained and stored. An interdisciplinary, international
AMS Board will comprehensively assess antibiotic treatment via review by a panel of experts.
After the observation is completed, stool samples will be batch-tested for intestinal
domination by the target pathogens of this study. Statistical analyses will be performed to
investigate an association between inappropriate antibiotic use as opposed to appropriate or
no antibiotic use and intestinal domination. If domination is detected, further analyses for
phenotype, quantity, resistance, and molecular biology will be performed. Finally, the
baseline sample will be tested for presence of the dominant species to understand the source
of the pathogen, i.e. nosocomial versus outpatient acquisition.
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