Correlation of High Seawater Temperature with Vibrio and Shewanella Infections, Denmark, 2010-2018.

During 2010-2018 in Denmark, 638 patients had Vibrio infections diagnosed and 521 patients had Shewanella infections diagnosed. Most cases occurred in years with high seawater temperatures. The substantial increase in those infections, with some causing septicemia, calls for clinical awareness and mandatory notification policies.

Epidemiology of gastrointestinal infections: lessons learned from syndromic testing, Region Zealand, Denmark.

The aim of this study was to investigate the value of syndromic diagnostic testing for a better understanding of the epidemiology of gastrointestinal infections in Denmark. Here we evaluated the QIAstat-Dx® Gastrointestinal (GI) Panel 1 assay on 18,610 fecal samples requested for analysis for enteric pathogens in Region Zealand, Denmark, in 1 year (October 1, 2021, to September 30, 2022). In total, 6905 (37%) samples were detected positive for one or more diarrhoeal bacteria, viruses, and protozoa. The most common bacterial, viral, and parasitic pathogens detected with the QIAstat-Dx® Gastrointestinal Panel 1 were EPEC (in patients ≥ 2 years of age) (n = 1420 (20.6%)), rotavirus (n = 948 (13.7%)), and Cryptosporidium spp. (n = 196 (2.84%)). We identified a large diversity in infections likely reflecting substantial differences in the epidemiology including origin of infections, mode of transmission, seasonality, age-dependent susceptibility to disease, severity, and travel history. All pathogens were detected as both single and coinfections. Viral infections peaked in March with a positive rate of 31.6%, and bacterial infections peaked in August with a positive rate of 35.3%. ETEC, Shigella/EIEC, EAEC, and P. shigelloides were most related to travel activity, and coinfections were frequent. The distribution of Ct values varied significantly between the pathogens, with the lowest Ct values (median 17-18) observed in astrovirus, adenovirus, and rotavirus. Our results highlight the value of providing extensive diagnostic testing on fecal samples for sufficient detection of relevant diarrhoeal pathogens for optimal clinical care.

Imported spring onions related to the first recorded outbreak of enteroinvasive Escherichia coli in Denmark, November to December 2021.

Between November and December 2021, the first ever recorded outbreak of enteroinvasive Escherichia coli in Denmark occurred at national scale. We describe the investigation of this outbreak, which was initially recognised in early December 2021. A total of 88 cases (58 female; 30 male) with a median age of 52 years (range: 0-91) were detected by PCR-based diagnostic methods. Case ascertainment was complicated by current culture-free diagnostic procedures, with only 34 cases confirmed by culture, serotyping and whole genome sequencing. Isolates from cases grouped into two serotypes (O136:H7 and O96:H19), which was supported by whole-genome-sequence-phylogeny, also yielding two clusters. Interviews of 42 cases and traceback investigation pointed towards consumption of ready-to-eat salads as the outbreak cause. While the ready-to-eat salads comprised different vegetables, imported spring onions were the only common ingredient and thus the likely source. Environmental investigations failed to recover outbreak strains. This report highlights the value of fast typing (here O-typing) to confirm cases in an outbreak situation. Timely communication and data sharing are also important, and were facilitated by the national collaboration between relevant laboratories, the public health institute and the veterinary and food administration. High hygiene standards for imported fresh vegetables intended for ready-to-eat products are essential.

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.

Verification of analytical bacterial spectrum of QIAstat-Dx® GI V2 and Novodiag® Bacterial GE+ V2-0 diagnostic panels.

BACKGROUND: Implementing multiplex PCR or syndromic panel-based testing platforms to detect microbial species that cause acute diarrhoea may guide patient management more effectively and efficiently. OBJECTIVES: To assess and compare the performance of two syndromic panel-based testing systems, QIAstat-Dx® Gastrointestinal Panel V2 (QGI) and the Novodiag® Bacterial GE+ V2-0 (NGE). METHODS: The QGI and NGE panels include 16 and 14 bacterial gastrointestinal pathogens, respectively. The performance of the panels was tested retrospectively using 141 positive clinical stool specimens, External Quality Assessment (EQA) panels and spiked faecal specimens. RESULTS: For Campylobacter jejuni and coli (n = 20), Salmonella (n = 24), Shigella (n = 13), Yersinia enterocolitica (non-1A biotypes) (n = 8), Clostridioides difficile (n = 24) and Vibrio parahaemolyticus (n = 2), QGI correctly verified 19/20, 20/24, 13/13, 8/8, 23/24 and 2/2, whereas NGE correctly verified 20/20, 17/24, 13/13, 8/8, 14/24 and 1/2. Among diarrhoeagenic Escherichia coli (n = 29), QGI reported one Shiga toxin-producing E. coli (STEC) stx1a O26:H11 as STEC serotype O157:H7 and NGE failed on one enteropathogenic E. coli, one enteroaggregative E. coli and one STEC (stx2e). Y. enterocolitica biotype 1A (non-pathogenic) (n = 6) were all positive in QGI, but negative in NGE. CONCLUSIONS: Both QGI and NGE testing panels can improve laboratory workflow and patient management by providing user-friendly platforms that can rapidly detect a number of targets with one specimen. QGI was significantly more sensitive in identifying C. difficile. Both methods had suboptimal detection of Salmonella and this needs to be examined further. The short hands-on time and turnaround time are of value for on-demand testing and use in a high-throughput setting.

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.

Whole genome sequencing data used for surveillance of Campylobacter infections: detection of a large continuous outbreak, Denmark, 2019.

BackgroundCampylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied.AimTyping-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks.MethodsWe performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat.ResultsSeventy-two clusters were detected, 58 small clusters (2-4 cases) and 14 large clusters (5-91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak.ConclusionOur WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases.

Whole-Genome Sequencing to Detect Numerous Campylobacter jejuni Outbreaks and Match Patient Isolates to Sources, Denmark, 2015-2017.

In industrialized countries, the leading cause of bacterial gastroenteritis is Campylobacter jejuni. However, outbreaks are rarely reported, which may reflect limitations of surveillance, for which molecular typing is not routinely performed. To determine the frequency of genetic clusters among patients and to find links to concurrent isolates from poultry meat, broiler chickens, cattle, pigs, and dogs, we performed whole-genome sequencing on 1,509 C. jejuni isolates from 774 patients and 735 food or animal sources in Denmark during 2015-2017. We found numerous clusters; 366/774 (47.3%) clinical isolates formed 104 clusters of >2 isolates. A total of 41 patient clusters representing 199/366 (54%) patients matched a potential source, primarily domestic chickens/broilers. This study revealed serial outbreaks and numerous matches to concurrent food and animal isolates and highlighted the potential of whole-genome sequencing for improving routine surveillance of C. jejuni by enhancing outbreak detection, source tracing, and potentially prevention of human infections.

Establishing a donor stool bank for faecal microbiota transplantation: methods and feasibility.

Faecal microbiota transplantation (FMT) is a promising treatment, but donor selection and implementation in clinical practice are difficult. Here, we describe the establishment of a donor stool bank based on the Tissue Act. Stool donors were recruited among blood donors and asked to donate five times in a month. A screening questionnaire, a medical interview and testing of blood and stool were conducted before and after donations. Donations were made at home and transported to the lab, where 50 g of stool was suspended and filtered in saline and 20-mL glycerol (final concentration of 10%) to a volume of 170 mL. The processed stool was assigned a batch number, frozen within 2 h after defecation and stored at - 80 °C for up to 1 year. All steps were documented and cross-checked before donor stool were released for clinical use. Thirteen donors were eligible at the first interview and started donations. Two donors were excluded due to a positive Helicobacter pylori test, two withdrew consent and one was lost to follow-up. One donor took a single dose of NSAIDs 2 days prior to a donation, which was discarded. There were no other excluding findings at the second interview or testing. Eight of the 13 donors were approved as stool donors. All donated five times with each donation yielding 1-6 portions. Eighty-four portions were released for clinical use. Recruiting stool donors among blood donors is safe and effective. The Tissue Act yields an appropriate regulative framework for FMT.

Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection.

OBJECTIVE: Gastroenteritis with Campylobacter concisus is an emerging infection, but the risk of irritable bowel syndrome (IBS) following it is unknown. MATERIAL AND METHODS: In a prospective, community-based study of gastroenteritis with C. concisus and C. jejuni/coli, we invited adult patients to participate in a questionnaire study, including IBS symptoms and psychometric scores, at baseline and at 6 months. We estimated adjusted RR (RRadj) (for age, sex and comorbidity) for IBS as the primary outcome. RESULTS: The development of IBS symptoms at 6 months was reported in 26/106 (25%) patients with C. concisus infection, and in 30/162 (19%) of C. jejuni/coli patients. The baseline predictors for IBS in C. concisus infection were high anxiety scores (RRadj 2.0; 95% CI 1.1-3.6, p<0.05), chills (RRadj 1.9; 95% CI 1.0-3.6, p<0.05), headache (RRadj 2.5; 95% CI 1.1-6.0, p<0.05), dizziness (RRadj 2.6; 95% CI 1.2-5.8, p<0.05) and muscle ache (RRadj 3.6; 95% CI 1.4-8.9, p<0.01). For all Campylobacter patients (n=268), we confirmed previous reports of anxiety (RRadj 2.0; 95% CI 1.3-3.1), depression (RRadj 2.3; 95% CI 1.3-4.0) and high somatization scores (RRadj 3.0; 95% CI 1.5-6.0) as predictors for post-infectious IBS (PI-IBS). CONCLUSIONS: Gastroenteritis with C. concisus carries a 25% risk of IBS at 6-month follow-up. The risk factors for IBS are chills, headache, dizziness and muscle ache in the acute stage, as well as preexisting high psychometric scores for anxiety. Our findings suggest that psychological factors play a role in the development of PI-IBS.

Rodent-adapted Cryptosporidium infection in humans: Seven new cases and review of the literature.

Cases of cryptosporidiosis in humans have been reported with strong indication of transmission from rodents. Here, we report seven new human cases of cryptosporidiosis involving rodent-adapted species (Cryptosporidium ditrichi [n = 1], Cryptosporidium mortiferum [n = 4; previously known as Cryptosporidium chipmunk genotype I], Cryptosporidium tyzzeri [n = 1], and Cryptosporidium viatorum [n = 1]) and review cases of human infection caused by these four species published to date. The seven new cases were detected in Denmark within a period of twelve months from 2022 to 2023. Only the C. tyzzeri and C. viatorum cases were associated with travel outside Denmark. The total number of human cases of cryptosporidiosis due to C. ditrichi and C. tyzzeri documented to date globally are still limited (4 and 7, respectively), whereas cases involving C. viatorum and C. mortiferum have been detected to a larger extent (43 and 63 cases, respectively). The four new cases of C. mortiferum were all of the XIVaA20G2T1 subtype, which is the only subtype identified so far in Scandinavia, and which is a subtype not yet found outside of Scandinavia. The new C. viatorum case was identified as the XVaA3g subtype. The C. tyzzeri case was subtyped as IXbA6. No subtype data were produced for C. ditrichi due to lack of a subtype assay. Review of existing data suggests the presence of C. ditrichi and C. mortiferum primarily in northern countries and C. tyzzeri and C. viatorum primarily in warmer climates. While our data may further support the role of Cryptosporidium as a cause of zoonotic disease, case descriptions should be obtained where possible to determine if Cryptosporidium species primarily adapted to rodents are the likely cause of symptoms or just an incidental finding.

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.

Evaluation of fecal calprotectin in Campylobacter concisus and Campylobacter jejuni/coli gastroenteritis.

Calprotectin (CP) is a calcium-binding cytosolic neutrophil protein and the concentration in feces reflects the migration of neutrophils into the gut lumen. Testing for fecal CP (f-CP) in patients with negative cultures for enteric pathogens is widely accepted as a useful screening tool for identifying patients who are most likely to benefit from endoscopy for suspected inflammatory bowel disease (IBD) with the assumption that a negative f-CP is compatible with a functional disorder. Campylobacter concisus has recently been reported to have a high incidence in the Danish population almost equal to Campylobacter jejuni and Campylobacter coli and has been reported to cause prolonged watery diarrhea. However, isolation of C. concisus from feces requires the filter method in a hydrogen-enriched microaerobic atmosphere, which is not commonly used in the laboratory, and the diagnosis may consequently be missed. The aim of this study was to evaluate the f-CP levels, as a marker for the intestinal inflammation in C. jejuni/coli- and C. concisus-infected patients. The authors found a high concentration of f-CP (median 631: IQR 221-1274) among 140 patients with C. jejuni/coli infection, whereas the f-CP level among 99 C. concisus-infected patients was significantly lower (median 53: IQR 20-169). The data correlate to the severe inflammatory gastroenteritis seen in patients infected with C. jejuni/coli, whereas C. concisus-infected patients have a much lower intestinal inflammation which could be compared with viral gastroenteritis. Nevertheless, clinicians should be aware of C. concisus infection, especially in patients with prolonged mild diarrhea, in the differential diagnosis to IBD.

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.

Seroreactivity to E. coli outer membrane protein C antibodies in active inflammatory bowel disease; diagnostic value and correlation with phylogroup B2 E. coli infection.

BACKGROUND: Several serologic tests, including anti-outer membrane porin C antibody (Omp C), are used for screening and as marker of disease course in inflammatory bowel diseases (IBD). Our aim was to investigate possible differences in Omp C level in patients with active and inactive IBD compared to controls. METHODS: All blood samples were tested for Omp C. Disease activity was evaluated by Harvey Bradshaw Index, Simple Clinical Activity Index and Modified Pouchitis Disease Activity Index. RESULTS: Blood samples were collected from 113 patients and 60 controls. Patients with active IBD did not have a higher level of Omp C than patients in remission. Surprisingly, in patients with active Crohn's disease a significantly lower level of Omp C was found compared with patients with inactive Crohn's disease (p < 0.05). All other groups among patients with IBD did have a significantly higher level of Omp C, compared with controls, including patients with acute gastroenteritis (p < 0.05). Although IBD patients with phylogroup B2 E. coli cultured from their fecal samples, were more likely to have a positive Omp C test (p < 0.05), this could not explain the low Omp C level in the subgroup of patients with active Crohn's disease. CONCLUSIONS: Omp C titer was not raised in patients with active IBD compared with patients in remission. In addition, there was no difference in Omp C level in patients with active Crohn's disease compared with controls. These observations do not support the use of Omp C serology testing, either in disease activity assessment, or in screening for active Crohn's disease.

A waterborne outbreak with a single clone of Campylobacter jejuni in the Danish town of Køge in May 2010.

BACKGROUND: In Denmark, large-scale waterborne outbreaks are rare. This report describes the investigation of an outbreak that occurred in the town of Køge in May 2010. METHODS: The epidemiological investigation consisted of hypothesis generating telephone interviews, followed by a cohort study among approximately 20,000 residents using an online questionnaire. Odds ratios were calculated for exposures including the number of glasses of tap water consumed. Geographical spreading was assessed using a geographical information system. The microbiological investigation included cultures of stool samples and flagellin-typing. In the environmental investigation, water samples were tested for Escherichia coli and coliform counts and for DNA of Campylobacter, Enterococcus, and Bacteroides. During the outbreak investigation a water boiling order was enforced, as tap water was considered a potential source. RESULTS: Of 45 patients with laboratory confirmed Campylobacter infection in the municipality of Køge in May, 43 lived in the area covered by the central water supply. Of 61 patients with laboratory confirmed Campylobacter jejuni by 8 June, 50 shared a common flagellin gene type--flaA type 36 (82%). The epidemic curve from the cohort study showed a wave of diarrhoea onset from 14 to 20 May (n = 176). Among these patients, the development of diarrhoea was associated with drinking tap water with a dose-response pattern (linear increase by 2 glasses: odds ratio 1.40, 95% confidence interval 1.16-1.70). No bacterial DNA was found in water samples. CONCLUSIONS: These findings indicated a point source contamination of tap water with a single clone of C. jejuni which likely occurred on 12-13 May. The water boiling order was lifted on 18 June.

The prevalence and clinical significance of intestinal parasites in HIV-infected patients in Denmark.

To investigate the prevalence and clinical significance of intestinal parasites in human immunodeficiency virus (HIV)-infected patients, faecal specimens from 96 HIV-infected patients were submitted to microbiological analyses, including microscopy and polymerase chain reaction for protozoa and enteropathogenic bacteria. Results of microbiological analyses were compared with self-reported gastrointestinal complaints collected using a validated questionnaire. Thirty-two (33%) patients were positive for parasites. However, opportunistic parasites (Isospora and Cryptosporidium) were detected in only 2 instances. Entamoeba dispar was detected in 10 cases, 9 of which represented men who have sex with men (MSM). Despite generally low HIV RNA loads and high CD4+ T-cell counts, 42% of the 76 patients reporting symptoms complained of diarrhoea, 31% of whom were parasite-positive. The presence of diarrhoea was not associated with the presence or absence of parasites; neither was it associated with receiving highly active anti-retroviral therapy (HAART) in general, or protease inhibitors (PI) in particular. A CD4+ T-cell count <200 cells/mm³ was not associated with parasitic infection or with diarrhoea. The data show that diarrhoea is a common symptom among HIV-infected patients in Denmark, but do not indicate that the diarrhoea is due to intestinal parasites.

Randomised clinical trial: a 12-strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections.

BACKGROUND: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT). AIMS: To compare the efficacy of a 12-strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open-label 3-arm randomised controlled trial. METHODS: We screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory-confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre-treated with vancomycin for 7-14 days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14 days. The vancomycin group was treated for 14 days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90 days. A secondary outcome was 180-day all-cause mortality. RESULTS: Participants in the FMT group (n = 34) were cured more often than participants receiving vancomycin (n = 31), 76% vs 45% (OR 3.9 (1.4-11.4), P < 0.01) or rectal bacteriotherapy (n = 31), 76% vs 52% (OR 3.0 (1.1-8.8), P = 0.04). Rectal bacteriotherapy and vancomycin performed similarly (P = 0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04-1.12), P = 0.07. CONCLUSIONS: Rectal bacteriotherapy appears as effective as vancomycin but less effective than 1-3 FMTs. FMT by enema with 1-3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality.

Disease-Specific Enteric Microbiome Dysbiosis in Inflammatory Bowel Disease.

Inflammatory Bowel disease (IBD) is traditionally divided into Crohn's disease (CD) and ulcerative colitis (UC). UC is a relapsing non-transmural inflammatory disease that is restricted to the colon and is characterized by flare-ups of bloody diarrhea. CD is a chronic, segmental localized granulomatous disease that can affect any part of the entire gastrointestinal tract. Ileo-anal pouch is a procedure restoring functionality of the rectum after a colectomy. IBD is a multifactorial disease and flares of IBD are probably triggered by changes in the intestinal microbiota followed by an abnormal immune response. In this study, we aim to analyze the intestinal bacterial diversity in IBD patients during various stages of disease compared with healthy controls. Permission for human experiments and recruitment of participants was obtained from the Ethic Committee for Copenhagen County hospitals (Permission no. KA-03019, Permission no. KA-20060159). Stools from 26 healthy controls, 42 CD, 38 UC and 18 pouch patients were collected. Stool DNA extraction was performed using Qiagen, DNA mini stool kit Denmark. DGGE-PCR amplifying the V2-V3 region of 16S-rDNA gene of the bacteria was amplified by universal primers HDA1 and HDA2. Analysis of DGGE was performed blinded using BioNumerics version 7.5. After normalization, a DGGE gel band matching was performed. The similarities between profiles were calculated with a ranked Pearson correlation coefficient based on the band matching results using band intensities. Simpson's index of diversity and Pielou's species evenness were calculated. Based on the Shannon Diversity Index, UC patients had lower species diversity and bacterial evenness in comparison to healthy persons, p < 0.05. However, only CD and disease pouch patients had lower species diversity compared to those with inactive disease and healthy controls. Well-functioning pouch patients had decreased species evenness in comparison to diseased pouch patients and control group. During the active disease stage in CD and pouch, the patients have a low bacterial diversity in their gut when compared to the inactive stage. In UC patients, a generally low diversity was observed at all stages of the disease compared to healthy controls.