Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova: A Randomized, Double-blinded, Placebo-controlled Clinical Trial (the PROCTO Trial).

BACKGROUND AND AIMS: To demonstrate that administration of 7500 Trichuris suis ova every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis. METHODS: A single-centre, randomized, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every two weeks for 24 weeks compared to placebo in moderate activity of ulcerative colitis (Mayo score 6-10) were performed. Primary outcome: Clinical remission. Secondary outcomes: Clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks and partial Mayo score over time. RESULTS: 119 patients were randomized to Trichuris suis ova (n=60) and placebo (n=59). At week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs. 34% of placebo-treated (RR=0.89; CI:0.52-1.50; p=0.80, ITT). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission of week 12 (p=0.01), and the partial Mayo score at week 14 and week 18 (p<0.05 and p=0.02). CONCLUSIONS: Compared to placebo, Trichuris suis ova was not superior in achieving clinical remission at week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at week 12.

The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).

BACKGROUND AND AIMS: To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. METHODS: The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. RESULTS: Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo. CONCLUSIONS: Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.

Multi-strain probiotics during pregnancy in women with obesity influence infant gut microbiome development: results from a randomized, double-blind placebo-controlled study.

Probiotics have been described to influence host health and prevent the risk of obesity by gut microbiome (GM) modulation. In a randomized double-blinded placebo-controlled feasibility study, we investigated whether Vivomixx® multi-strain probiotics administered to 50 women with obesity during pregnancy altered the GM composition and perinatal health outcomes of their infants up to 9 months after birth. The mothers and infants were followed up with four visits after birth: at 3 d, and at 3, 6, and 9 months after delivery. The infants were monitored by anthropometric measurements, fecal sample analysis, and questionnaires regarding health and diet.The study setup after birth was feasible, and the women and infants were willing to participate in additional study visits and collection of fecal samples during the 9-month follow-up. In total, 47 newborns were included for microbiome analysis.Maternal prenatal Vivomixx® administration did not alter infant GM diversity nor differential abundance, and the probiotic strains were not vertically transferred. However, the infant GM exhibited a decreased prevalence of the obesity-associated genera, Collinsella, in the probiotic group and of the metabolic health-associated Akkermansia in the placebo group, indicating that indirect community-scale effects of Vivomixx® on the GM of the mothers could be transferred to the infant.Moreover, 3 d after birth, the GM of the infant was influenced by mode of delivery and antibiotics administered during birth. Vaginally delivered infants had increased diversity and relative abundance of the metabolic health-associated Bifidobacterium and Bacteroides while having a decreased relative abundance of Enterococcus compared with infants delivered by cesarean section. Maternal antibiotic administration during birth resulted in a decreased relative abundance of Bifidobacteriumin the GM of the infants. In conclusion, this study observed potential effects on obesity-associated infant GM after maternal probiotic supplementation.

Older and younger adults differ in time course of skill acquisition but not in overall improvement in a bimanual visuomotor tracking task.

Manual motor performance declines with age, but the extent to which age influences the acquisition of new skills remains a topic of debate. Here, we examined whether older healthy adults show less training-dependent performance improvements during a single session of a bimanual pinch task than younger adults. We also explored whether physical and cognitive factors, such as grip strength or motor-cognitive ability, are associated with performance improvements. Healthy younger (n = 16) and older (n = 20) adults performed three training blocks separated by short breaks. Participants were tasked with producing visually instructed changes in pinch force using their right and left thumb and index fingers. Task complexity was varied by shifting between bimanual mirror-symmetric and inverse-asymmetric changes in pinch force. Older adults generally displayed higher visuomotor force tracking errors during the more complex inverse-asymmetric task compared to younger adults. Both groups showed a comparable net decrease in visuomotor force tracking error over the entire session, but their improvement trajectories differed. Young adults showed enhanced visuomotor tracking error only in the first block, while older adults exhibited a more gradual improvement over the three training blocks. Furthermore, grip strength and performance on a motor-cognitive test battery scaled positively with individual performance improvements during the first block in both age groups. Together, the results show subtle age-dependent differences in the rate of bimanual visuomotor skill acquisition, while overall short-term learning ability is maintained.

Rheumatoid arthritis and risk of osteoarticular infection and death following Staphylococcus aureus bacteraemia: A nationwide cohort study.

OBJECTIVES: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA. METHODS: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-2018. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants, antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression). RESULTS: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1%(95%CI 18.8; 27.6) for patients with RA and 12.5%(12.1; 13.0) for patients without RA (non-RA) (HR 1.93(1.54; 2.41)). For RA patients with orthopaedic implants cumulative incidence was 29.4%(22.9; 36.2) (HR 1.75(1.08; 2.85), and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9%(27.0; 56.1) (HR 2.27(1.29; 3.98) compared with non-users). All-cause 90-day mortality following SAB was similar in RA (35.4%(30.6; 40.3)) and non-RA (33.9%(33.2; 34.5), HR 1.04(0.87; 1.24)). CONCLUSION: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI.

The association between bacteriuria and adverse pregnancy outcomes: a systematic review and meta-analysis of observational studies.

BACKGROUND: Antibiotics for bacteriuria and urinary tract infection are commonly prescribed during pregnancy to avoid adverse pregnancy outcomes. The aim of this study was to evaluate the association between significant bacteriuria in pregnancy and any of the four pregnancy outcomes: preterm delivery; low birth weight; small for gestational age; and preterm labour. METHODS: Systematic review with meta-analysis of observational studies. We searched PubMed, EMBASE, the Cochrane CENTRAL library, and Web of Science for observational studies published before 1 March 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. Study identification, data extraction and risk-of-bias assessment was performed by two independent authors. We combined the included studies in meta-analyses and expressed results as ORs with 95% CIs (Prospero CRD42016053485). RESULTS: We identified 58 studies involving 421 657 women. The quality of the studies was mainly poor or fair. The pooled, unadjusted OR for the association between any significant bacteriuria and: (i) preterm delivery was 1.62 (95% CI: 1.30-2.01; 27 studies; I2 = 61%); (ii) low birth weight was 1.50 (95% CI: 1.30-1.72; 47 studies; I2 = 74%); (iii) preterm labour was 2.29 (95% CI: 1.53-3.43; 3 studies; I2 = 0%); and (iv) small for gestational age was 1.33 (95% CI: 0.88-2.02; 7 studies; I2 = 54%). Four studies provided an adjusted OR, but were too diverse to combine in meta-analysis. CONCLUSIONS: This systematic review identified an association between significant bacteriuria in pregnancy and the three complications: preterm delivery; low birth weight; and preterm labour. However, the quality of the available evidence is insufficient to conclude whether this association is merely due to confounding factors. There is a lack of high-quality evidence to support active identification and treatment of bacteriuria in pregnancy.

Metal-Organic Framework Glass as a Functional Filler Enables Enhanced Performance of Solid-State Polymer Electrolytes for Lithium Metal Batteries.

Polymers are promising candidates as solid-state electrolytes due to their performance and processability, but fillers play a critical role in adjusting the polymer network structure and electrochemical, thermal, and mechanical properties. Most fillers studied so far are anisotropic, limiting the possibility of homogeneous ion transport. Here, applying metal-organic framework (MOF) glass as an isotropic functional filler, solid-state polyethylene oxide (PEO) electrolytes are prepared. Calorimetric and diffusion kinetics tests show that the MOF glass addition reduces the glass transition temperature of the polymer phase, improving the mobility of the polymer chains, and thereby facilitating lithium (Li) ion transport. By also incorporating the lithium salt and ionic liquid (IL), Li-Li symmetric cell tests of the PEO-lithium salt-MOF glass-IL electrolyte reveal low overpotential, indicating low interfacial impedance. Simulations show that the isotropic structure of the MOF glass facilitates the wettability of the IL by enhancing interfacial interactions, leading to a less confined IL structure that promotes Li-ion mobility. Finally, the obtained electrolyte is used to construct Li-lithium iron phosphate full batteries that feature high cycle stability and rate capability. This work therefore demonstrates how an isotropic functional filler can be used to enhance the electrochemical performance of solid-state polymer electrolytes.

Video aided extinction measurement: A competitive method for dust density diagnostics.

Among the most popular methods to measure dust density in a laboratory setup are 1D extinction, Abel inversion for circularly symmetric geometries, and computer tomography (CT) for arbitrary geometries. We present a new method based on a 1D extinction measurement in correlation with a video taken at an acute angle. It works well with limited optical access and has a good time resolution (at least several hertz). It measures the dust density within a slice of a nanodust cloud with precision comparable to other methods. Depending on the setup, this video aided extinction measurement can replace CT.

Remote Estimation of Peripheral Oxygen Saturation and Pulse Rate From Facial Analysis Using a Smartphone Camera.

Vital sign monitoring is an invaluable tool for healthcare professionals, both in the hospital and at home. Traditional measurement devices provide accurate readings but require physical contact with the patient which often is unsuitable, furthermore contact-based devices have been reported to fail by loosing contact due to movement as severe events occur, therefore, a contactless method is necessary.We hypothesize that, in ideal scenarios, it is possible to estimate both SpO2 and pulse rate using only facial video recorded with a smartphone's front-facing camera. To test this hypothesis, a dataset of 10 healthy subjects performing various breathing patterns while being recorded with a smartphone camera was collected during ideal lighting conditions.Using advanced image and signal processing methods to acquire remote photoplethysmography (rPPG) estimates from a patient's forehead, our proposed method can achieve SpO2 estimation results with Arms = 1.34% (accuracy RMS) and MAE ± STD = 1.26 ± 0.68% (mean average error) across a SpO2 range of 92% to 99% (percentage point SpO2) and pulse rate estimation results with Arms = 3.91 bpm (beats per minute) and MAE ± STD = 3.24±2.11 bpm across a pulse rate range of 60 bpm to 90 bpm. We conclude from these results, that remote vital sign estimation using facial videos recorded entirely with a smartphone camera is possible.

Lacticaseibacillus rhamnosus GG Versus Placebo for Eradication of Vancomycin-Resistant Enterococcus faecium in Intestinal Carriers: A Systematic Review and Meta-Analysis.

The aim of this review was to assess the efficacy and safety of Lacticaseibacillus rhamnosus GG (LGG) (previously known as Lactobacillus rhamnosus GG) for the eradication of vancomycin-resistant Enterococcus faecium (VREfm) in colonized carriers. We searched Cochrane Central, EMBASE, and the PubMed Library from inception to 21 August 2023, for randomized controlled trials (RCTs) investigating the effectiveness of LGG for the eradication of gastrointestinal carriage of VREfm. An initial screening was performed followed by a full-text evaluation of the papers. Out of 4076 articles in the original screening, six RCTs (167 participants) were included in the review. All were placebo-controlled RCTs. The meta-analysis was inconclusive with regard to the effect of LGG for clearing VREfm colonization. The overall quality of the evidence was low due to inconsistency and the small number of patients in the trials. We found insufficient evidence to support the use of LGG for the eradication of VREfm in colonized carriers. There is a need for larger RCTs with a standardized formulation and dosage of LGG in future trials.

Risk factors for methicillin-resistant Staphylococcus aureus colonization in a level-IV neonatal intensive care unit: a retrospective study.

Objective: To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization in neonatal patients during an MRSA outbreak to minimize future outbreaks. Design: Retrospective case-control study. Setting: Level-IV neonatal intensive care unit (NICU) at Copenhagen University Hospital, Rigshospitalet, Denmark. Patients: Neonates with either MRSA or methicillin-susceptible Staphylococcus aureus (MSSA). Methods: Methicillin-resistant Staphylococcus aureus-positive neonates were matched with those colonized or infected with MSSA in a 1:1 ratio. The control group was selected from clinical samples, whereas MRSA-positive neonates were identified from clinical samples or from screening. A total of 140 characteristics were investigated to identify risk factors associated with MRSA acquisition. The characteristics were categorized into three categories: patient, unit, and microbiological characteristics. Results: Out of 1,102 neonates screened for MRSA, between December 2019 and January 2022, 33 were MRSA positive. They were all colonized with an MRSA outbreak clone (spa type t127) and were included in this study. Four patients (12%) had severe infection. Admission due to respiratory diseases, need for intubation, need for peripheral venous catheters, admission to shared rooms with shared toilets and bath facilities in the aisles, and need for readmission were all correlated with later MRSA colonization (P < 0.05). Conclusion: We identified clinically relevant diseases, procedures, and facilities that predispose patients to potentially life-threatening MRSA infections. A specific MRSA reservoir remains unidentified; however, these findings have contributed to crucial changes in our NICU to reduce the number of MRSA infections and future outbreaks.

No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study.

BACKGROUND AND AIMS: Modulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring. METHODS AND RESULTS: A randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27-30 and 36-37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed. Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group. CONCLUSION: In this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring. This study was registered at clinicaltrials.gov as NCT02508844.

Antibiotic-free vaginal microbiota transplant with donor engraftment, dysbiosis resolution and live birth after recurrent pregnancy loss: a proof of concept case study.

Background: Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics. Methods: This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a Lactobacillus-dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an in vitro microbiome competition assay. Findings: A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1 s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of Gardnerella spp. After one VMT there was a complete shift in microbiome composition to 81.2% L. crispatus and 9% L. jensenii with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term. Interpretation: Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required. Funding: The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark.

The association between Staphylococcus aureus colonization on cheek skin at 2†months and subsequent atopic dermatitis in a prospective birth cohort.

BACKGROUND: Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. OBJECTIVES: To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. METHODS: In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. RESULTS: At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. CONCLUSIONS: It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

An Endogenous Staphylococcus aureus CRISPR-Cas System Limits Phage Proliferation and Is Efficiently Excised from the Genome as Part of the SCCmec Cassette.

CRISPR-Cas is an adaptive immune system that allows bacteria to inactivate mobile genetic elements. Approximately 50% of bacteria harbor CRISPR-Cas; however, in the human pathogen Staphylococcus aureus, CRISPR-Cas loci are less common and often studied in heterologous systems. We analyzed the prevalence of CRISPR-Cas in genomes of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in Denmark. Only 2.9% of the strains carried CRISPR-Cas systems, but for strains of sequence type ST630, over half were positive. All CRISPR-Cas loci were type III-A and located within the staphylococcal cassette chromosome mec (SCCmec) type V(5C2&5), conferring ß-lactam resistance. Curiously, only 23 different CRISPR spacers were identified in 69 CRISPR-Cas positive strains, and almost identical SCCmec cassettes, CRISPR arrays, and cas genes are present in staphylococcal species other than S. aureus, suggesting that these were transferred horizontally. For the ST630 strain 110900, we demonstrate that the SCCmec cassette containing CRISPR-Cas is excised from the chromosome at high frequency. However, the cassette was not transferable under the conditions investigated. One of the CRISPR spacers targets a late gene in the lytic bacteriophage phiIPLA-RODI, and we show that the system protects against phage infection by reducing phage burst size. However, CRISPR-Cas can be overloaded or circumvented by CRISPR escape mutants. Our results imply that the endogenous type III-A CRISPR-Cas system in S. aureus is active against targeted phages, albeit with low efficacy. This suggests that native S. aureus CRISPR-Cas offers only partial immunity and in nature may work in tandem with other defense systems. IMPORTANCE CRISPR-Cas is an adaptive immune system protecting bacteria and archaea against mobile genetic elements such as phages. In strains of Staphylococcus aureus, CRISPR-Cas is rare, but when present, it is located within the SCCmec element, which encodes resistance to methicillin and other ß-lactam antibiotics. We show that the element is excisable, suggesting that the CRISPR-Cas locus is transferable. In support of this, we found almost identical CRISPR-Cas-carrying SCCmec elements in different species of non-S. aureus staphylococci, indicating that the system is mobile but only rarely acquires new spacers in S. aureus. Additionally, we show that in its endogenous form, the S. aureus CRISPR-Cas is active but inefficient against lytic phages that can overload the system or form escape mutants. Thus, we propose that CRISPR-Cas in S. aureus offers only partial immunity in native systems and so may work with other defense systems to prevent phage-mediated killing.

Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS. AIM: To assess the efficacy and safety of FMT for the treatment of IBS. METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence. RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision. CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.

A Clinically Selected Staphylococcus aureus clpP Mutant Survives Daptomycin Treatment by Reducing Binding of the Antibiotic and Adapting a Rod-Shaped Morphology.

Daptomycin is a last-resort antibiotic used for the treatment of infections caused by Gram-positive antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Treatment failure is commonly linked to accumulation of point mutations; however, the contribution of single mutations to resistance and the mechanisms underlying resistance remain incompletely understood. Here, we show that a single nucleotide polymorphism (SNP) selected during daptomycin therapy inactivates the highly conserved ClpP protease and is causing reduced susceptibility of MRSA to daptomycin, vancomycin, and ß-lactam antibiotics as well as decreased expression of virulence factors. Super-resolution microscopy demonstrated that inactivation of ClpP reduced binding of daptomycin to the septal site and diminished membrane damage. In both the parental strain and the clpP strain, daptomycin inhibited the inward progression of septum synthesis, eventually leading to lysis and death of the parental strain while surviving clpP cells were able to continue synthesis of the peripheral cell wall in the presence of 10× MIC daptomycin, resulting in a rod-shaped morphology. To our knowledge, this is the first demonstration that synthesis of the outer cell wall continues in the presence of daptomycin. Collectively, our data provide novel insight into the mechanisms behind bacterial killing and resistance to this important antibiotic. Also, the study emphasizes that treatment with last-line antibiotics is selective for mutations that, like the SNP in clpP, favor antibiotic resistance over virulence gene expression.

The Clinical Efficacy, Safety, and Tolerability of Vancomycin for the Treatment of Recurrent Clostridioides difficile Infection - A Systematic Review.

Introduction: The aim of this systematic review of randomized clinical trials (RCTs) was to examine the efficacy, safety, and tolerability of vancomycin for treatment of recurrent Clostridioides difficile infection (rCDI). Methods: The PubMed database was searched from inception to August 23, 2022. An initial screening was performed followed by a full-text evaluation of the papers. Inclusion criteria were RCTs investigating vancomycin for treatment of rCDI. Results: A total of six studies and 269 patients were included in the review. Three studies used a fixed dose regimen of vancomycin, one study used pulse regimen, one study used a taper-and-pulse regimen, and one study used a taper-and-pulse regimen for the participants with two or more recurrences. The resolution of infection varied from 19% to 58.3% in five of six studies reporting this as an outcome. Four out of six studies reported new episodes of rCDI as an intervention outcome, in those studies 50-63% of participants experienced rCDI. Regarding the safety and tolerability of vancomycin treatment for rCDI, one study described several adverse events regarding gastrointestinal discomfort along with fatigue and skin rash. There were no records of serious adverse events in the included studies. Conclusion: While oral vancomycin is mostly safe and well tolerated in the RCTs reviewed here, the efficacy for treating rCDI varies greatly from 19-58.3%, and 50-63% of participants experienced new episodes of rCDI.

Community-acquired Staphylococcus aureus meningitis in adults.

BACKGROUND: Staphylococcus aureus is an uncommon cause of community-acquired bacterial meningitis. We aimed to describe patients with this disease. METHODS: We evaluated clinical characteristics and outcome of adults with community-acquired S. aureus meningitis from prospective nationwide cohort studies from Denmark (2015-2020) and the Netherlands (2006-2021). Whole genome sequencing of S. aureus isolates was performed to evaluate the potential association between clonal complex and clinical characteristics. RESULTS: We evaluated 111 episodes of community-acquired S. aureus meningitis: 65 from Denmark and 46 from the Netherlands. The median age was 66 years (interquartile range [IQR] 50-74) and 43 of 111 patients were female (39%). Concomitant infectious foci were found in 95 of 107 patients (89%), most commonly endocarditis (53 of 109 [49%]) and spondylodiscitis (43 of 109 [39%]). The triad of neck stiffness, altered mental status (Glasgow Coma Scale score <14), and fever was present in only 18 of 108 patients (17%). Surgery was performed in 14 of 33 patients (42%) with spondylodiscitis and 26 of 52 (50%) with endocarditis. A favorable outcome (Glasgow Outcome Scale score 5) occurred in 26 of 111 patients (23%), while 39 (35%) died. The most common bacterial clonal complexes (CC) were CC30 (16 [17%]), CC45 (16 [17%]), CC5 (12 [13%], and CC15 (10 [11%]); no associations between CCs and concomitant foci or outcome were found. CONCLUSIONS: Community-acquired S. aureus meningitis is a severe disease with a high case fatality rate, occurring mainly in patients with concomitant endocarditis or spondylodiscitis.

Complete Genome Sequences of Extraintestinal Pathogenic Escherichia coli Clinical Isolates from Danish Ulcerative Colitis Patients.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a potential factor in ulcerative colitis etiology. We report here the complete genome and plasmid sequences of three Escherichia coli isolates, C 237-04 (p7), C 236-04A (p10A), and C 691-04A (p19A), obtained from fecal samples from ulcerative colitis patients in Copenhagen, Denmark.