Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.

Background: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality. Methods: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt. Results: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI. Conclusions: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.

Comparison of the Risk of Recurrent Clostridioides Difficile Infections Among Patients in 2018 Versus 2013.

Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had ≥1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P < .0001).

Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients.

In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.

The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.

Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.

Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy. We therefore assessed a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality. METHODS: We did a pragmatic, randomised, parallel-group, multicentre trial in ten hospitals in Africa--four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe. Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis (fever, cough, night sweats, or self-reported weightloss) and illness severity necessitating admission to hospital. Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment. We randomly assigned patients (1:1) to either LAM plus routine diagnostic tests for tuberculosis (smear microscopy, Xpert-MTB/RIF, and culture; LAM group) or routine diagnostic tests alone (no LAM group) using computer-generated allocation lists in blocks of ten. All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere, USA) at the bedside on enrolment. On the basis of a positive test result, the nurses made a recommendation for initiating anti-tuberculosis treatment. The attending physician made an independent decision about whether to start treatment or not. Neither patients nor health-care workers were masked to group allocation and test results. The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population (those who received their allocated intervention). This trial is registered with ClinicalTrials.gov, number NCT01770730. FINDINGS: Between Jan 1, 2013, and Oct 2, 2014, we screened 8728 patients and randomly assigned 2659 to treatment (1336 to LAM, 1323 to no LAM). 108 patients did not receive their allocated treatment, mainly because they did not meet the inclusion criteria, and 23 were excluded from analysis, leaving 2528 in the final modified intention-to-treat analysis (1257 in the LAM group, 1271 in the no LAM group). Overall all-cause 8-week mortality occurred in 578 (23%) patients, 261 (21%) in LAM and 317 (25%) in no LAM, an absolute reduction of 4% (95% CI 1-7). The risk ratio adjusted for country was 0·83 (95% CI 0·73-0·96), p=0·012, with a relative risk reduction of 17% (95% CI 4-28). With the time-to-event analysis, there were 159 deaths per 100 person-years in LAM and 196 per 100 person-years in no LAM (hazard ratio adjusted for country 0·82 [95% CI 0·70-0·96], p=0·015). No adverse events were associated with LAM testing. INTERPRETATION: Bedside LAM-guided initiation of anti-tuberculosis treatment in HIV-positive hospital inpatients with suspected tuberculosis was associated with reduced 8-week mortality. The implementation of LAM testing is likely to offer the greatest benefit in hospitals where diagnostic resources are most scarce and where patients present with severe illness, advanced immunosuppression, and an inability to self-expectorate sputum. FUNDING: European Developing Clinical Trials Partnership, the South African Medical Research Council, and the South African National Research Foundation.

A Ru(II) bis-terpyridine-like complex that catalyzes water oxidation: the influence of steric strain.

The complexation of 2,9-dicarboxy-1,10-phenanthroline (DPA) with [Ru(tpy)Cl3] (tpy = 2,2';6,2″-terpyridine) provides a six-coordinate species in which one carboxyl group of DPA is not bound to the Ru(II) center. A more soluble tri-t-butyl tpy analogue is also prepared. Upon oxidation, neither species shows evidence for intramolecular trapping of a seven-coordinate intermediate. The role of the tpy ligand is revealed by the preparation of [Ru(tpy)(phenq)](2+) (phenq = 2-(quinol-8'-yl)-1,10-phenanthroline) that behaves as an active water oxidation catalyst (TON = 334). This activity is explained by the expanded coordination geometry of the phenq ligand that can form a six-membered chelate ring that better accommodates the linear arrangement of axial ligands required for optimal pentagonal bipyramid geometry. When a 1,8-naphthyidine ring is substituted for each of the two peripheral pyridine rings on tpy, increased crowding in the vicinity of the metal center impedes acquisition of the prerequisite reaction geometry.