In this issue, CMI features the first randomized controlled trial assessing a decolonization regimen of oral antibiotics followed by a faecal microbiota transfer (FMT) for the eradication of multidrugresistant Enterobacteriaceae from the human intestinal tract [1]. The authors are to be congratulated for taking up the challenge of conducting this trial in a highly complex and rapidly changing regulatory environment. There was no statistically significant advantage for the intervention group, but the study of Huttner et al. should be placed in a historical context, as the study was well designed and only suffered from inclusion of insufficient patients.Based on the results of this published study, one might wonder whether there truly is potential for the eradication of Gram-negative multidrug-resistant organisms (MDRO), including extended-spectrum b-lactamase, carbapenemase-producing Enterobacteriaceae, and non-fermenters (Pseudomonas and Acinetobacter spp.), as well as associated antibiotic-resistance genes (ARG) through the manipulation of the gut microbiota. It remains largely unknown which conditions predispose to their acquisition and specifically how the microbiota may facilitate or prevent this event. Transition from colonization to infection with MDRO may be of clinical relevance for non-immunocompromised patients, such as individuals who are at risk for development of ventilator-associated pneumonia, cathether-associated urinary tract infections or bloodstream infections. However, it is of more importance in significantly immunocompromised patients, such as solid organ transplant and stem cell recipients, as well as patients receiving intensive chemotherapy. These individuals are considered an important target population for eradication strategies. Unfortunately, severely immunocompromised patients and solid organ transplant patients were excluded in the study of Huttner et al. [1].There are many uncertainties on the efficacy of eradication therapies for Gram-negative MDRO. So far, all eradication strategies based on the use of orally non-absorbable antibiotics have failed, and a recently completed ESCMID guideline does not recommend this approach [2]. Nevertheless, we believe that manipulation of the gut microbiota could rely on a broad range of other interventions. The administration of prebiotics or probiotics, FMTs, synthetic microbial communities or bacteriolytic phages has not been sufficiently assessed for its potential efficacy.The presence of MDRO in the intestinal tract of patients with recurrent Clostridium difficile infections (CDI) and the success of FMT, prompted observations on the application of FMT to eradicate MDRO in individuals with CDI. On average, people with CDI harbour greater numbers and a more diverse set of ARG than healthy controls. ARG sub-studies of individuals receiving FMT for the treatment of recurrent CDI have shown significant reductions in the quantity of ARG after FMT [3e5]. However, none of these studies included control groups, and the patients with recurrent CDI hav...