Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens (PILGRIM)



Vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), and Clostridium difficile have become an immediate threat to hospitalized patients worldwide. Although surveillance and control programmes are in place in many countries to mitigate transmission of these drug-resistant organisms in the healthcare setting, the impact of the VRE/EPE/C. difficile epidemic on individual patients entering the healthcare system is poorly understood.

Ongoing project

There is a scarcity of trials defining the impact of the VRE/EPE/C. difficile epidemic on individual patients newly entering the healthcare-system. It is unknown to what degree infection control (IC) and antimicrobial stewardship (AMS) interventions can disrupt the presumed chain of events (acquisition, colonization, antibiotic selective pressure, and intestinal domination) leading to infections with these microorganisms. Herein, we describe a comprehensive, multinational, multi-centre clinical study programme to elucidate the impact of the VRE/EPE/C. difficile epidemic on patients at high risk of healthcare-associated infections, during which we will observe the clinical and pathophysiological events leading to infection, analyse the preventative potential of IC and AMS, establish the preventable burden of these microorganisms, and better understand when and why AMS/IC measures are not always effective.

Centrepieces of the study will be rating of adequateness of antibiotic treatments by an international AMS-board and in-depth analysis of intestinal microbiota before and after antibiotic exposure. We hypothesize that receiving inadequate treatment places patients at high risk of intestinal domination and thus infection by these microorganisms. Further analyses will address costeffectiveness of specific interventions, behavioural analyses of the decision process leading to inadequate antibiotic treatment, and the rate of undetected previous colonization by EPE/VRE/C. difficile falsely attributed as hospital-acquired when conventional screening methods are used.

Project partners

  • Jörg Janne Vehreschild, University Hospital of Cologne, Germany (Coordinator)
  • Noa Eliakim Raz, Rabin Medical Center, Israel
  • Uga Dumpis, University of Latvia, Latvia
  • Gunnar Skov Simonsen, University Hospital of North Norway , Norway
  • Christian Giske, Karolinska Institutet, Sweden
  • Makeda Semret, McGill University Health Centre (MGU), Canada

The gut flora includes millions of bacteria and other microorganisms which naturally contribute to keep the human body healthy. It is mainly located in the colon (large intestine). Alimentary habits, diseases, and the use of antibiotics or other drugs may modify the number and type of bacteria in the gut flora. Antibiotics save many lives by curing patients with bacterial infections such as pneumonias or urinary infections. After oral or intravenous administration, antibiotics enter the bloodstream, are transported to the site of infection (for example, in the lungs or in urine) and kill the bacteria causing the infection. Small amounts of antibiotics also reach the colon and the bacteria of the gut flora. There, some bacterial species may be killed; other species may abnormally overgrow, resulting in domination of the flora, or become resistant to antibiotics.

The number of antimicrobial resistant bacteria has increased dramatically among patients worldwide. So-called vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE) are a large threat for hospitalised patients worldwide. Similarly, the burden of “healthcare associated” infectious diarrhoea caused by a Clostridium difficile infection (CDI) has increased as well, resulting in longer treatments and higher risks for re-hospitalisation. For these reasons, it is important to use antibiotics only when they are really needed. If an antibiotic is required, it should be carefully selected to be effective against the bacteria causing the infection while preserving the healthy gut flora as much as possible.

There are initiatives that support doctors in choosing the best antibiotic by training, educational materials and prescription regulations, called Antimicrobial Stewardship. Another approach to reduce the spread of multi-resistant bacteria are hygiene and infection control measures. However, these measures come with considerable cost and effort during a time of limited healthcare resources. It remains unknown which measures are the most effective to prevent spread of resistance bacteria and ensure optimal antibiotic treatment. We also need more information on how much antibiotics contribute to spread of EPE, VRE and C. difficile and whether appropriate, rational antibiotic use could help improving the current situation.

The objective of the present PILGRIM study is to – determine the impact of antimicrobial prescription on the gut flora by EPE or VRE or infection with C. difficile – determine how often and when gut colonization by EPE or VRE and/or C. difficile occurs in-hospital or before admission – determine what measures (e.g. Infection Control or Antimicrobial Stewardship) are the most effective strategies to prevent healthcare-acquired colonization and infection by VRE, EPE, and C. difficile.