scholarly journals Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms

Author(s):  
Rohma Ghani ◽  
Benjamin H Mullish ◽  
Julie A K McDonald ◽  
Anan Ghazy ◽  
Horace R T Williams ◽  
...  

Abstract Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia, and length of stay in 20 patients colonized/infected with MDRO receiving FMT (compared with pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.

2020 ◽  
Vol 8 (2) ◽  
pp. 166 ◽  
Author(s):  
Amy Feehan ◽  
Julia Garcia-Diaz

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.


2015 ◽  
Vol 53 (6) ◽  
pp. 1986-1989 ◽  
Author(s):  
Nancy F. Crum-Cianflone ◽  
Eva Sullivan ◽  
Gonzalo Ballon-Landa

We report a case in which fecal microbiota transplantation (FMT) utilized for relapsingClostridium difficilecolitis successfully eradicated colonization with several multidrug-resistant organisms (MDROs). FMT may have an additive benefit of reducing MDRO carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyondC. difficile.


mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Danielle Barrios Steed ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex D. Waldman ◽  
Ahmed Babiker ◽  
...  

ABSTRACT Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility. IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.


2019 ◽  
Vol 70 (1) ◽  
pp. 335-351 ◽  
Author(s):  
R.E. Ooijevaar ◽  
E.M. Terveer ◽  
H.W. Verspaget ◽  
E.J. Kuijper ◽  
J.J. Keller

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile infection. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed.


2020 ◽  
Vol 15 (12) ◽  
pp. 1173-1183
Author(s):  
Gianluca Ianiro ◽  
Jonathan P Segal ◽  
Benjamin H Mullish ◽  
Mohammed N Quraishi ◽  
Serena Porcari ◽  
...  

Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S1-S1
Author(s):  
Michael Woodworth ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex Waldman ◽  
Rachel Friedman-Moraco ◽  
...  

Abstract Background Decreases in multidrug-resistant organism (MDRO) colonization and antibiotic resistance gene abundance have been reported after fecal microbiota transplantation (FMT), but data on clinical microbiology culture and susceptibility results after FMT are limited. Methods We retrospectively reviewed the available microbiology results for patients who underwent FMT for recurrent Clostridioides difficile infection (RCDI) at Emory University from July 7, 2012 until December 2017 and had microbiology results within 1 year pre- and post-FMT. Demographic and clinical characteristics were abstracted by trained reviewers, and statistical tests of differences in central tendency were tested with Wilcoxon signed-rank tests. Results Of 236 unique patients undergoing FMT during the study period, 18 had growth of Gram-negative bacteria on culture pre- and post-FMT. Of these, 8 had Gram-negative growth in urine culture (the most common site) pre- and post-FMT. Fourteen (14/18, 78%) patients were female, 4/18 (22%) were black, 14/22 (78%) were white, and 18/18 (100%) were non-Hispanic. The mean number of CDI episodes prior to first FMT was 4 (range 3–7 episodes). Differences in counts of susceptible, intermediate, and resistant susceptibility test results before and after FMT are shown in Figures 1 and 2. Although a trend in reduction of resistant reports is visually suggested, this was not statistically significant by Wilcoxon signed-rank testing (P = 0.10 for all cultures, P = 0.21 for urine). Ten patients had pre-FMT micro results and no micro results after FMT, but reduction of count of infectious syndromes in FMT could not be tested with this study design. Abstraction of viral quantitative PCR results did not suggest clinical recognition of new infection or reactivation of viruses after FMT. Conclusion FMT may reduce clinical burden of antimicrobial resistance, but statistically significant differences in resistance were not detected in this study. Further study with RCTs is needed. Disclosures All authors: No reported disclosures.


Author(s):  
Andrew J. Innes ◽  
Benjamin H. Mullish ◽  
Rohma Ghani ◽  
Richard M. Szydlo ◽  
Jane F. Apperley ◽  
...  

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.


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