Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria

Abstract

Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in ten adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). Median age at fecal microbiota transplantation was 48 (range, 16-64) years. Three patients needed a second transplant from the same donor due to initial failure of the procedure. With a median follow up of 13 (range, 4-40) months, decolonization was achieved in seven of ten patients. In all patients, fecal micro-biota transplantation was safe: one patient presented with constipation during the first five days after FMT and two patients had grade I diarrhea. One case of gut grade III acute graft- versus -host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

“…Another small retrospective case-matched study of 20 patients in France showed 80% (8/10) of patients cleared CRE or CRE/Acinetobacter colonization 14 days after FMT versus 20% (2/10) in the control group [24]. In other small studies (n = 8 to 20) with various endpoints, the effectiveness of decolonization ranged from 20% to 93% [1,[25][26][27][28][29]. One study by Davido et al suggests that based on an 87% decolonization rate of VRE at three months, FMT should be further explored to combat outbreaks within hospitals [30].…”

“…Furthermore, if any microbiome therapy is going to be used for MDRO treatment or prevention, clear guidelines for use in gram-positive versus gram-negative infections and various mechanisms of resistance are necessary, as FMT has not been particularly efficacious with MDR gram-negative bacteria so far [44,45]. Some have speculated that FMT could be less effective for ESBL decolonization, although the mechanism by which this is possible has yet to be defined [25,58]. Finally, research needs to show more than a lack of inferiority; rather, studies should be designed to measure outcomes where FMT or probiotic therapies could show an advantage beyond acute treatment (e.g., reduced readmission, fewer subsequent infections, and fewer long-term complications).…”

The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

“…One possible reason why patients with C. difficile and co-colonized with Candida species may not respond to FMT is that C. albicans has also been shown to affect gut bacterial reconstitution or recolonization after antibiotic administration [19]. Given that FMT has become an attractive treatment strategy, not only for C. difficile infection or GI disorders but also to mitigate other treatmentrelated toxicities such as GvHD, immune checkpoint inhibitor-associated colitis, and antibiotic resistant infection, one must consider the fungal contribution to the effectiveness of this strategy [41][42][43][44].…”

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease

“…Similar findings were reported by Battipaglia et al, who performed FMT by enema or Table 1 FMT studies in HSCT recipients for the treatment of CDI. nasogastric tube in 10 patients before (n = 4) or after (n = 6) allogeneic HSCT [75]. Overall, the bulk of data indicate that FMT is safe in HSCT recipients and its use may extend beyond the treatment of recurrent CDI.…”