scholarly journals Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Danielle Barrios Steed ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex D. Waldman ◽  
Ahmed Babiker ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Fecal Microbiota Transplantation ◽  
Antibiotic Prescription ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Gram Negative ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Susceptibility Profiles

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.

scholarly journals 109. Differences in Gram-Negative Antibiotic Susceptibility Among Patients Receiving Fecal Microbiota Transplant for Clostridioides difficile

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S1-S1
Author(s):  
Michael Woodworth ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex Waldman ◽  
Rachel Friedman-Moraco ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Statistical Tests ◽  
Antibiotic Resistance Gene ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Resistant Organism ◽  
Fecal Microbiota Transplant ◽  
Gram Negative ◽  
Clostridioides Difficile ◽  
Signed Rank

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.

scholarly journals Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 714
Author(s):  
Supapit Wongkuna ◽  
Tavan Janvilisri ◽  
Matthew Phanchana ◽  
Phurt Harnvoravongchai ◽  
Amornrat Aroonnual ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Reference Strain ◽  
Toxin Production ◽  
Temporal Variations ◽  
Toxin Gene ◽  
Data Sets ◽  
Clostridioides Difficile ◽  
Life Threatening ◽  
Susceptibility Profiles

Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A−B+CDT− (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT− (8%), five A−B+CDT+ (19%), seven A−B+CDT− (27%), and six A−B−CDT− (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand.

scholarly journals Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-Negative Bacilli: a Comparison of Disk Diffusion to Broth Microdilution

2020 ◽  
Vol 59 (1) ◽  
pp. e01649-20 ◽  
Author(s):  
C. Paul Morris ◽  
Yehudit Bergman ◽  
Tsigedera Tekle ◽  
John A. Fissel ◽  
Pranita D. Tamma ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Antimicrobial Susceptibility Testing ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Alternative Approach

ABSTRACTAntimicrobial susceptibility testing (AST) of cefiderocol poses challenges because of its unique mechanism of action (i.e., requiring an iron-depleted state) and due to differences in interpretative criteria established by the Clinical and Laboratory Standards Institute (CLSI), U.S. Food and Drug Administration (FDA), and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Our objective was to compare cefiderocol disk diffusion methods (DD) to broth microdilution (BMD) for AST of Gram-negative bacilli (GNB). Cefiderocol AST was performed on consecutive carbapenem-resistant Enterobacterales (CRE; 58 isolates) and non-glucose-fermenting GNB (50 isolates) by BMD (lyophilized panels; Sensititre; Thermo Fisher) and DD (30 μg; research-use-only [RUO] MASTDISCS and FDA-cleared HardyDisks). Results were interpreted using FDA (prior to 28 September 2020 update), EUCAST, and investigational CLSI breakpoints (BPs). Categorical agreement (CA), minor errors (mE), major errors (ME), and very major errors (VME) were calculated for DD methods. The susceptibilities of all isolates by BMD were 72% (FDA), 75% (EUCAST) and 90% (CLSI). For DD methods, EUCAST BPs demonstrated lower susceptibility at 65% and 66%, compared to 74% and 72% (FDA) and 87% and 89% (CLSI) by HardyDisks and MASTDISCS, respectively. CA ranged from 75% to 90%, with 8 to 25% mE, 0 to 19% ME, and 0 to 20% VME and varied based on disk, GNB, and BPs evaluated. Both DD methods performed poorly for Acinetobacter baumannii complex. There is considerable variability when cefiderocol ASTs are interpreted using CLSI, FDA, and EUCAST breakpoints. DD offers a convenient alternative approach to BMD methods for cefiderocol AST, with the exception of A. baumannii complex isolates.

scholarly journals Clinical Application and Potential of Fecal Microbiota Transplantation

2019 ◽  
Vol 70 (1) ◽  
pp. 335-351 ◽  
Author(s):  
R.E. Ooijevaar ◽  
E.M. Terveer ◽  
H.W. Verspaget ◽  
E.J. Kuijper ◽  
J.J. Keller
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Graft Versus Host ◽  
Clostridioides Difficile ◽  
Current State ◽  
Randomized Controlled Studies ◽  
Clostridioides Difficile Infection ◽  
New Treatment ◽  
Irritable Bowel

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.

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders

2020 ◽  
Vol 15 (12) ◽  
pp. 1173-1183
Author(s):  
Gianluca Ianiro ◽  
Jonathan P Segal ◽  
Benjamin H Mullish ◽  
Mohammed N Quraishi ◽  
Serena Porcari ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Current Evidence ◽  
Resistant Bacteria ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Inflammatory Bowel ◽  
Irritable Bowel

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.

scholarly journals Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig Haifer ◽  
Sudarshan Paramsothy ◽  
Thomas J. Borody ◽  
Annabel Clancy ◽  
Rupert W. Leong ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Fungal Species ◽  
Health Concern ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Gut Colonization ◽  
The Impact

ABSTRACT Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics. IMPORTANCE Clostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.

scholarly journals Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Jennifer M. Auchtung ◽  
Eva C. Preisner ◽  
James Collins ◽  
Armando I. Lerma ◽  
Robert A. Britton
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Content Type ◽  
Susceptibility To Infection ◽  
Clostridioides Difficile ◽  
Fold Reduction ◽  
Clostridioides Difficile Infection ◽  
Community Types

ABSTRACT The gastrointestinal microbiome plays an important role in limiting susceptibility to infection with Clostridioides difficile. To better understand the ecology of bacteria important for C. difficile colonization resistance, we developed an experimental platform to simplify complex communities of fecal bacteria through dilution and rapidly screen for their ability to resist C. difficile colonization after challenge, as measured by >100-fold reduction in levels of C. difficile in challenged communities. We screened 76 simplified communities diluted from cultures of six fecal donors and identified 24 simplified communities that inhibited C. difficile colonization in vitro. Sequencing revealed that simplified communities were composed of 19 to 67 operational taxonomic units (OTUs) and could be partitioned into four distinct community types. One simplified community could be further simplified from 56 to 28 OTUs through dilution and retain the ability to inhibit C. difficile. We tested the efficacy of seven simplified communities in a humanized microbiota mouse model. We found that four communities were able to significantly reduce the severity of the initial C. difficile infection and limit susceptibility to disease relapse. Analysis of fecal microbiomes from treated mice demonstrated that simplified communities accelerated recovery of indigenous bacteria and led to stable engraftment of 19 to 22 OTUs from simplified communities. Overall, the insights gained through the identification and characterization of these simplified communities increase our understanding of the microbial dynamics of C. difficile infection and recovery. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.

scholarly journals Complete Genome Sequence of Multidrug-ResistantPlesiomonas shigelloidesStrain MS-17-188

2018 ◽  
Vol 6 (18) ◽  
Author(s):  
Hossam Abdelhamed ◽  
Ozan Ozdemir ◽  
Hasan C. Tekedar ◽  
Mark A. Arick ◽  
Chuan-Yu Hsu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Plesiomonas Shigelloides ◽  
Content Type

ABSTRACTPlesiomonas shigelloidesis a Gram-negative bacterium isolated from diverse environments. Here, we describe the complete genome sequence of the multidrug-resistantP. shigelloidesstrain MS-17-188, isolated from a diseased catfish. Availability of this genome will be beneficial for characterizing the molecular mechanisms of antibiotic resistance in this strain.

scholarly journals Fecal Microbiota Transplantation and Successful Resolution of Multidrug-Resistant-Organism Colonization

2015 ◽  
Vol 53 (6) ◽  
pp. 1986-1989 ◽  
Author(s):  
Nancy F. Crum-Cianflone ◽  
Eva Sullivan ◽  
Gonzalo Ballon-Landa
Keyword(s):  
Clostridium Difficile ◽  
Fecal Microbiota Transplantation ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Resistant Organism ◽  
Content Type ◽  
Multidrug Resistant Organisms ◽  
Successful Resolution ◽  
Potential Measure

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.

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