Clinical and microbiological characteristics of anaerobic bacteremia during 1994-2019: A Danish population-based cohort study.

OBJECTIVES: Bacteremia with anaerobic bacteria is generally a marker of severe prognosis. However, population-based data is lacking. Our aim was to describe the epidemiology and the 30-day mortality rate of anaerobic bacteremia in a Danish population-based setting. METHODS: In this population-based cohort study, all first-time episodes of anaerobic bacteremia from the North Denmark Bacteremia Research Database during 1994-2019 were identified. Information on comorbidities, discharge diagnoses, and mortality was retrieved. 30-day mortality rates were calculated and a multivariate logistic regression analysis to identify risk factors for death was performed. RESULTS: 1750 episodes with anaerobic bacteremia were identified, corresponding to an incidence rate of 12.5 per 100,000 inhabitants (increasing from 11.2 in 1994-2014 to 17.7 in 2015-2019). Of these episodes, a third were polymicrobial, and the majority (70 %) of patients had one or more comorbid conditions. Abdominal infection was the source of bacteremia in 61 % of patients, while it was unknown for 15 %. The most frequently isolated genera were Bacteroides (45 %), Clostridium (20 %) and Fusobacterium (6 %). The overall crude 30-day mortality rate was 27 %, but rates were even higher for patients of high age, with liver disease, and solid tumors. The odds ratio (OR) for 30-day mortality was 1.32 for Clostridium species, and 1.27 for polymicrobial bacteremia with aerobic bacteria. CONCLUSIONS: The incidence rate of anaerobic bacteremia increased, and the 30-day mortality rate remained high during the study period. Multiple factors influence 30-day mortality rates, including high age, liver disease, solid tumor, polymicrobial bacteremia, and bacteremia with Clostridium species.

Impact of COVID-19 Restrictions on Incidence of Enteropathogenic Bacteria, Virus, and Parasites in Denmark: A National, Register-Based Study.

Diarrheal diseases caused by enteric pathogens are a significant public health concern. It is widely considered that close contact between persons, poor hygiene, and consumption of contaminated food are the primary causes of gastroenteritis. Clinical microbiology laboratory observations indicate that the incidence of enteropathogenic microorganisms may have been reduced in Denmark during the COVID-19 pandemic. All Departments of Clinical Microbiology in Denmark provided data on the monthly incidence of Salmonella spp., Escherichia coli, Campylobacter spp., Clostridioides difficile, Norovirus GI+GII, Giardia duodenalis, and Cryptosporidium from March 2018 to February 2021. The data were divided into three periods as follows: Control Period 1 (March 2018 to February 2019); Control Period 2 (March 2019 to February 2020); and the Restriction (pandemic) Period (March 2020 to February 2021). The incidences of pathogenic Salmonella spp.-, Escherichia coli-, and Campylobacter spp.-positive samples decreased by 57.3%, 48.1%, and 32.9%, respectively, during the restriction period. No decrease in C. difficile was observed. Norovirus GI+GII-positive samples decreased by 85.6%. Giardia duodenalis-positive samples decreased by 66.2%. Cryptosporidium species decreased by 59.6%. This study demonstrates a clear decrease in the incidence of enteropathogenic bacteria (except for C. difficile), viruses, and parasites during the SARS-CoV-2 restriction period in Denmark.

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.

Fecal microbiota is associated with extraintestinal manifestations in inflammatory bowel disease.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitney's test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p < .05) and included important health-associated bacteria, such as Agathobacter and Faecalibacterium. CONCLUSIONS: The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.

Salmonella infections in Denmark from 2013-2022 with focus on serotype distribution, invasiveness, age, sex, and travel exposition.

PURPOSE: To analyze the nationwide incidence of Salmonella infections in Denmark from 2013 to 2022. METHODS: Confirmed cases of Salmonella enterica subsp. enterica were examined using the National Register of Enteric Pathogens during 2013-2022. Proportions, incidence rates (IR), relative risk (RR), and 95% confidence intervals (CI) were calculated to assess differences in serotypes, invasiveness, age, sex, and travel exposure. RESULTS: We identified 9,944 Danish Salmonella enterica subsp. enterica cases, with an average annual incidence rate of 16.9 per 100,000 inhabitants, declining during the COVID-19 pandemic. Typhoidal cases totaled 206, with an average annual IR of 0.35 per 100,000 inhabitants. Enteric fever patients had a median age of 24 years (IQR:17-36). Leading non-typhoid Salmonella (NTS) serotypes were S. Enteritidis (26.4%), monophasic S. Typhimurium (16.5%), and S. Typhimurium (13.5%). Median age for NTS cases was 42 (IQR: 18-62), with even sex distribution, and a third reported travel prior to onset of disease. The overall percentage of invasive NTS (iNTS) infection was 8.1% (CI: 7.6-8.7). Eleven serotypes were associated with higher invasiveness, with S. Dublin and S. Panama having the highest invasiveness with age and sex-adjusted RR of 7.31 (CI: 6.35-8.43) and 5.42 (CI: 3.42-8.60), respectively, compared to all other NTS serotypes. Increased age was associated with higher RR for iNTS infection. CONCLUSION: During the decade, there was a limited number of typhoidal cases. The dominant NTS serotypes were S. Enteritidis and monophasic S. Typhimurium, whereas S. Dublin and S. Panama exhibited the highest invasive potential.

Vertebral osteomyelitis caused by Campylobacter jejuni in an immunocompetent patient.

BACKGROUND: Campylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide. However, systemic infection with C. jejuni is uncommon, and osteomyelitis caused by C. jejuni is extremely rare. Cultivation from spinal bone biopsies has not previously been reported in the literature. CASE PRESENTATION: A 79-year-old immunocompetent male was admitted to the emergency department at Aalborg University Hospital in Denmark with lower back pain, fever and diarrhoea. A FecalSwab obtained upon admission was PCR-positive for Campylobacter spp, while an aerobic blood culture bottle was positive for C. jejuni (Time to detection: 70.4 h). A MRI of columna totalis showed osteomyelitis at L1/L2 with an epidural abscess from L1 to L2 with compression of the dura sack. The patient underwent spinal surgery with spondylodesis and decompression of L1/L2. The surgery was uncomplicated and the discus material was also culture positive for C. jejuni. The patient was treated with meropenem for a total duration of four weeks, followed by four weeks of oral treatment with clindamycin in tapered dosage. The patient recovered quickly following surgery and targeted antibiotic treatment with decreasing lumbar pain and biochemical response and was fully recovered at follow-up three months after end of treatment. CONCLUSIONS: While C. jejuni osteomyelitis is rare, it should still be suspected as a possible causative bacterial aetiology in patients with vertebral osteomyelitis, in particular when symptoms of diarrhoea is involved in the clinical presentation. Susceptibility testing is crucial due to emerging resistance, and targeted treatment strategies should rely upon such tests.

Evaluating the diagnostic accuracy and clinical utility of 16S and 18S rRNA gene targeted next-generation sequencing based on five years of clinical experience.

BACKGROUND: The use of 16S/18S rRNA targeted next-generation sequencing (tNGS) has improved microbial diagnostics, however, the use of tNGS in a routine clinical setting requires further elucidation. We retrospectively evaluated the diagnostic accuracy and clinical utility of 16S/18S tNGS, routinely used in the North Denmark Region between 2017 and 2021. METHODS: We retrieved 544 tNGS results from 491 patients hospitalised with suspected infection (e.g. meningitis, pneumonia, intraabdominal abscess, osteomyelitis and joint infection). The tNGS assays was performed using the Illumina MiSeq desktop sequencer, and BION software for annotation. The patients' diagnosis and clinical management was evaluated by medical chart review. We calculated sensitivity and specificity, and determined the diagnostic accuracy of tNGS by defining results as true positive, true negative, false positive, and false negative. RESULTS: Overall, tNGS had a sensitivity of 56% and a specificity of 97%. tNGS was more frequently true positive compared to culture (32% vs 18%), and tNGS detected a greater variety of bacteria and fungi, and was more frequently polymicrobial. However, the total diagnostic turnaround time was 16 days, and although 73% of tNGS results were true positive or true negative, only 4.4% of results led to changes in clinical management. CONCLUSIONS: As a supplement to culture, tNGS improves identification of pathogenic microorganisms in a broad range of clinical specimens. However, the long turnaround time of tNGS in our setting may have contributed to a limited clinical utility. An improved turnaround time can be the key to improved clinical utility in a future setting.

Herpes simplex virus infection among neonates suspected of invasive bacterial infection: a population-based cohort study.

OBJECTIVE: To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections. DESIGN: A nationwide population-based cohort study. SETTING: All neonatal and paediatric emergency departments in Denmark from 1 January 2010 to 31 December 2019. PATIENTS: Neonates aged 0-28 days with HSV infection. MAIN OUTCOME MEASURES: The main outcome measures were incidence and NNT. The NNT was calculated based on neonates with invasive HSV infection whose onset symptoms resembled IBI and the estimated number of Danish neonates who received antibiotics for suspected IBI. RESULTS: Fifty-four neonates with HSV infection were identified, that is, an incidence of 9 per 100 000 live births. Twenty presented with symptoms resembling IBI, all within the first 14 days of life. Of 18 (78%) neonates, 14 had elevated C reactive protein, 14 of 19 (74%) had elevated alanine aminotransferase and 11 of 17 (65%) had thrombocytopaenia. The estimated NNTs with empiric acyclovir at postnatal ages 0-3, 4-7 and 8-14 days were 1139 (95% CI 523 to 3103), 168 (95% CI 101 to 726) and 117 (95% CI 48 to 198), respectively. CONCLUSIONS: The incidence of neonatal HSV infection was higher than in previous decades; however, the estimated NNT with empiric acyclovir was high. Therefore, we propose not to treat all neonates suspected of IBI with empiric acyclovir, as current European guidelines suggest. However, HSV should be considered in neonates with signs of infection, especially after the third postnatal day and in neonates with high alanine aminotransferases and thrombocytopaenia.

The incidence of laboratory-confirmed cases of enteric pathogens in Denmark 2018: a national observational study.

BACKGROUND: Only a subset of enteric pathogens is under surveillance in Denmark, and knowledge on the remaining pathogens detected in acute gastroenteritis is limited. Here, we present the one-year incidence of all enteric pathogens diagnosed in Denmark, a high-income country, in 2018 and an overview of diagnostic methods used for detection. METHODS: All 10 departments of clinical microbiology completed a questionnaire on test methods and provided 2018-data of persons with positive stool samples with Salmonella species, Campylobacter jejuni/coli, Yersinia enterocolitica, Aeromonas species, diarrheagenic Escherichia coli (Enteroinvasive (EIEC), Shiga toxin-producing (STEC), Enterotoxigenic (ETEC), Enteropathogenic (EPEC), and intimin-producing/attaching and effacing (AEEC)), Shigella species., Vibrio cholerae, norovirus, rotavirus, sapovirus, adenovirus, Giardia intestinalis, Cryptosporidium species, and Entamoeba histolytica. RESULTS: Enteric bacterial infections were diagnosed with an incidence of 229.9 cases/100,000 inhabitants, virus had an incidence of 86/100,000 and enteropathogenic parasites of 12.5/100,000. Viruses constituted more than half of diagnosed enteropathogens for children below 2 years and elderly above 80 years. Diagnostic methods and algorithms differed across the country and in general PCR testing resulted in higher incidences compared to culture (bacteria), antigen-test (viruses), or microscopy (parasites) for most pathogens. CONCLUSIONS: In Denmark, the majority of detected infections are bacterial with viral agents primarily detected in the extremes of ages and with few intestinal protozoal infections. Incidence rates were affected by age, clinical setting and local test methods with PCR leading to increased detection rates. The latter needs to be taken into account when interpreting epidemiological data across the country.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

A rare Danish case of Yersinia pseudotuberculosis pyogenic liver abscess.

Yersinia pseudotuberculosis is a rare Gram-negative bacillus that cause enterocolitis and terminal ileitis. We report the first Danish case with Y. pseudotuberculosis multiple pyogenic liver abscess presenting with 6 weeks intermittently fever, fatigue, and weight loss. The patient was successfully treated with percutaneous drainage and intravenous piperacillin/tazobactam and oral ciprofloxacin.

[Ureaplasma parvum arthritis affecting knee, hip, and sacroiliac joint].

In this case report a rare case of Ureaplasma parvum arthritis affecting the left knee, hip, and the sacroiliac joint in a 57-year-old woman is investigated. The patient was initially treated with intravenous piperacillin/tazobactam and later on meropenem with no clinical effect. After surgery of the hip and knee, tissue biopsies and synovial fluids were all culture negative. Eventually, Ureaplasma parvum was detected by 16S analysis, and the antibiotic regimen was changed to intravenous moxifloxacin. The patient improved and after four weeks the therapy was changed to lifelong oral therapy with moxifloxacin.

One Day in Denmark: Comparison of Phenotypic and Genotypic Antimicrobial Susceptibility Testing in Bacterial Isolates From Clinical Settings.

Antimicrobial susceptibility testing (AST) should be fast and accurate, leading to proper interventions and therapeutic success. Clinical microbiology laboratories rely on phenotypic methods, but the continuous improvement and decrease in the cost of whole-genome sequencing (WGS) technologies make them an attractive alternative. Studies evaluating the performance of WGS-based prediction of antimicrobial resistance (AMR) for selected bacterial species have shown promising results. There are, however, significant gaps in the literature evaluating the applicability of WGS as a diagnostics method in real-life clinical settings against the range of bacterial pathogens experienced there. Thus, we compared standard phenotypic AST results with WGS-based predictions of AMR profiles in bacterial isolates without preselection of defined species, to evaluate the applicability of WGS as a diagnostics method in clinical settings. We collected all bacterial isolates processed by all Danish Clinical Microbiology Laboratories in 1 day. We randomly selected 500 isolates without any preselection of species. We performed AST through standard broth microdilution (BMD) for 488 isolates (n = 6,487 phenotypic AST results) and compared results with in silico antibiograms obtained through WGS (Illumina NextSeq) followed by bioinformatics analyses using ResFinder 4.0 (n = 5,229 comparisons). A higher proportion of AMR was observed for Gram-negative bacteria (10.9%) than for Gram-positive bacteria (6.1%). Comparison of BMD with WGS data yielded a concordance of 91.7%, with discordant results mainly due to phenotypically susceptible isolates harboring genetic AMR determinants. These cases correspond to 6.2% of all isolate-antimicrobial combinations analyzed and to 6.8% of all phenotypically susceptible combinations. We detected fewer cases of phenotypically resistant isolates without any known genetic resistance mechanism, particularly 2.1% of all combinations analyzed, which corresponded to 26.4% of all detected phenotypic resistances. Most discordances were observed for specific combinations of species-antimicrobial: macrolides and tetracycline in streptococci, ciprofloxacin and ß-lactams in combination with ß-lactamase inhibitors in Enterobacterales, and most antimicrobials in Pseudomonas aeruginosa. WGS has the potential to be used for surveillance and routine clinical microbiology. However, in clinical microbiology settings and especially for certain species and antimicrobial agent combinations, further developments in AMR gene databases are needed to ensure higher concordance between in silico predictions and expected phenotypic AMR profiles.

One Day in Denmark: Nationwide point-prevalence survey of human bacterial isolates and comparison of classical and whole-genome sequence-based species identification methods.

OBJECTIVES: Implementing whole-genome sequencing (WGS) technologies in clinical microbiology laboratories can increase the amount and quality of information available for healthcare practitioners. In this study, we analysed the applicability of this method and determined the distribution of bacterial species processed in clinical settings in Denmark. METHODS: We performed a point-prevalence study of all bacterial isolates (n = 2,009) processed and reported in the Clinical Microbiology Laboratories in Denmark in one day in January 2018. We compared species identification as performed by classical methods (MALDI-TOF) and by bioinformatics analysis (KmerFinder and rMLST) of WGS (Illumina NextSeq) data. We compared the national point-prevalence of bacterial isolates observed in clinical settings with the research attention given to those same genera in scientific literature. RESULTS: The most prevalent bacterium was Escherichia coli isolated from urine (n = 646), followed by Staphylococcus spp. from skin or soft tissues (n = 197). The distribution of bacterial species throughout the country was not homogeneous. We observed concordance of species identification for all methods in 95.7% (n = 1,919) of isolates, furthermore obtaining concordance for 99.7% (n = 1,999) at genus level. The number of scientific publications in the country did not correlate with the number of bacterial isolates of each genera analysed in this study. CONCLUSIONS: WGS technologies have the potential to be applied in clinical settings for routine diagnostics purposes. This study also showed that bioinformatics databases should be continuously improved and results from local point-prevalence surveys should not be applied at national levels without previously determining possible regional variations.

Sentinel surveillance and epidemiology of Clostridioides difficile in Denmark, 2016 to 2019.

BackgroundSince 2008, Danish national surveillance of Clostridioides difficile has focused on binary toxin-positive strains in order to monitor epidemic types such as PCR ribotype (RT) 027 and 078. Additional surveillance is needed to provide a more unbiased representation of all strains from the clinical reservoir.AimSetting up a new sentinel surveillance scheme for an improved understanding of type distribution relative to time, geography and epidemiology, here presenting data from 2016 to 2019.MethodsFor 2─4 weeks in spring and autumn each year between 2016 and 2019, all 10 Danish Departments of Clinical Microbiology collected faecal samples containing toxigenic C. difficile. Isolates were typed at the national reference laboratory at Statens Serum Institut. The typing method in 2016-17 used tandem-repeat-sequence typing, while the typing method in 2018-19 was whole genome sequencing.ResultsDuring the study period, the sentinel surveillance scheme included ca 14-15% of all Danish cases of C. difficile infections. Binary toxin-negative strains accounted for 75% and 16 of the 20 most prevalent types. The most common sequence types (ST) were ST2/13 (RT014/020) (19.5%), ST1 (RT027) (10.8%), ST11 (RT078) (6.7%), ST8 (RT002) (6.6%) and ST6 (RT005/117) (5.1%). The data also highlighted geographical differences, mostly related to ST1 and temporal decline of ST1 (p = 0.0008) and the increase of ST103 (p = 0.002), ST17 (p = 0.004) and ST37 (p = 0.003), the latter three binary toxin-negative.ConclusionSentinel surveillance allowed nationwide monitoring of geographical differences and temporal changes in C. difficile infections in Denmark, including emerging types, regardless of binary toxin status.

Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota.

BACKGROUND: Microscopic colitis (MC), an inflammatory disease of the colon, is characterized by chronic non-bloody diarrhea with characteristic inflammation and for some, collagen deposits in mucosal biopsies. The etiology of MC is unclear, although previous findings implicate luminal factors and thus the gut microbiome. However, the relationships between fecal microbiota and MC are relatively unexplored. METHODS: Stool microbiota of MC (n = 15) and healthy controls (HC; n = 21) were assessed by 16S rRNA V4 amplicon sequencing and analysis performed in QIIME. Gut microbiota functions were predicted using Piphillin and inflammatory potential assessed using an in vitro HT29 colonocyte cell assay. RESULTS: MC patient fecal microbiota were less diverse (Faiths index; p < 0.01) and compositionally distinct (PERMANOVA, weighted UniFrac, R2 = 0.08, p = 0.02) compared with HC subjects. MC microbiota were significantly depleted of members of the Clostridiales, enriched for Prevotella and more likely to be dominated by this genus (Chi2 = 0.03). Predicted pathways enriched in MC microbiota included those related to biosynthesis of antimicrobials, and sphingolipids, to glycan degradation, host defense evasion, and Th17 cell differentiation and activation. In vitro, exposure of cultured colonocytes to cell-free products of MC patient feces indicates reduced gene expression of IL-1B and occludin and increased GPR119 and the lymphocyte chemoattractant CCL20. CONCLUSION: MC gut microbiota are distinct from HC and characterized by lower bacterial diversity and Prevotella enrichment and distinct predicted functional pathways. Limited in vitro experiments indicate that compared with cell-free products from healthy fecal microbiota, MC microbiota induce distinct responses when co-cultured with epithelial cells, implicating microbiota perturbation in MC-associated mucosal dysfunction.

Danish Whole-Genome-Sequenced Candida albicans and Candida glabrata Samples Fit into Globally Prevalent Clades.

Candida albicans and Candida glabrata are opportunistic fungal pathogens with increasing incidence worldwide and higher-than-expected prevalence in Denmark. We whole-genome sequenced yeast isolates collected from Danish Clinical Microbiology Laboratories to obtain an overview of the Candida population in the country. The majority of the 30 C. albicans isolates were found to belong to three globally prevalent clades, and, with one exception, the remaining isolates were also predicted to cluster with samples from other geographical locations. Similarly, most of the eight C. glabrata isolates were predicted to be prevalent subtypes. Antifungal susceptibility testing proved all C. albicans isolates to be susceptible to both azoles and echinocandins. Two C. glabrata isolates presented azole-resistant phenotypes, yet all were susceptible to echinocandins. There is no indication of causality between population structure and resistance phenotypes for either species.

Three cases of Sutterella wadsworthensis bacteremia secondary to abdominal infections.

The anaerobic bacterium Sutterella wadsworthensis has previously been isolated from the human intestine, both in healthy individuals and patients with gastrointestinal disorders, and the clinical significance of this bacterium is unknown. In this case report, we describe three cases of bacteremia with Sutterella wadsworthensis, from patients with recent intraabdominal surgery.

A case of blaNDM-1-positive Salmonella Kottbus, Denmark, November 2020.

We present a case of carbapenemase-producing blaNDM-1-positive Salmonella Kottbus in an 82-year-old Danish man. The blaNDM-1 was also identified in Escherichia coli and Citrobacter freundii in the same patient on the same 43 kb IncN2 plasmid, suggesting in vivo inter-species plasmid transfer. A NCBI BLAST analysis of the plasmid (pAMA003584_NDM-1) identified 12 highly similar plasmids, all originating from east and south-east Asia. This case could be the first confirmed case of blaNDM-1-positive Salmonella not related to travel outside Europe.

Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT).

Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.