Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile - a German multicentre cohort study (IBIS).

OBJECTIVES: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) following initial infection in patients with Clostridioides difficile (C. difficile) from a German multicentre cohort study. METHODS: The IBIS multicentre cohort enrolled patients with an index episode of CDI between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within ten days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. RESULTS: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within ten days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event-free. The Cox proportional hazards model revealed differences in EFS for the overall population and both sub-groups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% Cl 0.33-0.65]; non-severe: HR 0.39; [95% Cl 0.24-0.60]; severe: HR 0.52; [95% Cl 0.28-0.95]). CONCLUSIONS: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared to metronidazole across all severity levels.

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

T Cell Response After SARS-CoV-2 Vaccination in Immunocompromised Patients with Inflammatory Bowel Disease.

BACKGROUND: Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease [IBD] patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD patients. METHODS: Totals of 28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first, and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response, including IFN-γ and TNF-α response and antibody titres, were analysed. RESULTS: Overall, 71.4% of the IBD patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml [p = 0.329] after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared with healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in healthy donorsn [HD] and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed. CONCLUSIONS: Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

Inflammatory Bowel Disease in the COVID-19 Pandemic: the Patients' Perspective.

BACKGROUND: The coronavirus disease 2019 [COVID-19] pandemic is affecting lives worldwide. The influence of inflammatory bowel disease [IBD] medication and IBD itself on COVID-19 is controversial. Additionally, IBD-focused guidance is scarce. OBJECTIVE: Our aims were to determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD [N = 415] at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants [N = 116], was performed. RESULTS: Patients with IBD had a high fear of infection. This was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD-focused COVID-19 information should be actively conveyed.

Microbial Spectrum of Intra-Abdominal Abscesses in Perforating Crohn's Disease: Results from a Prospective German Registry.

BACKGROUND: Intra-abdominal abscesses [IAAs] are common life-threatening complications in patients with Crohn's disease [CD]. In addition to interventional drainage and surgical therapy, empirical antibiotic therapy represents a cornerstone of treatment, but contemporary data on microbial spectra and antimicrobial resistance are scarce. METHODS: We recruited 105 patients with CD and IAAs from nine German centres for a prospective registry in order to characterize the microbiological spectrum, resistance profiles, antibiotic therapy and outcome. RESULTS: In 92 of 105 patients, microbial investigations of abscess material revealed pathogenic microorganisms. A total of 174 pathogens were isolated, with a median of 2 pathogens per culture [range: 1-6]. Most frequently isolated pathogens were E. coli [45 patients], Streptococcus spp. [28 patients], Enterococci [27 patients], Candida [13 patients] and anaerobes [12 patients]. Resistance to third-generation cephalosporins, penicillins with beta-lactamase inhibitors and quinolones were observed in 51, 36 and 35 patients, respectively. Seven patients had multiple-drug-resistant bacteria. Thirty patients received inadequate empirical treatment, and this was more frequent in patients receiving steroids or immunosuppression [37%] than in patients without immunosuppression [10%: p = 0.001] and was associated with a longer hospital stay [21 days vs 13 days, p = 0.003]. CONCLUSION: Based on antimicrobial resistance profiles, we herein report a high rate of inadequate empirical first-line therapy for IAAs in CD, especially in patients receiving immunosuppression, and this is associated with prolonged hospitalization.

Soluble urokinase plasminogen activator receptor is compartmentally regulated in decompensated cirrhosis and indicates immune activation and short-term mortality.

OBJECTIVE: Patients with decompensated cirrhosis are susceptible to bacterial infections, which are associated with organ failure and a high mortality rate. Reliable biomarkers are needed to identify patients who require intensified treatment. Our objective was to study the regulation and prognostic relevance of elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) in patients with advanced cirrhosis. DESIGN, SETTING AND PARTICIPANTS: We examined the associations between serum and ascitic fluid (AF) suPAR and liver function, bacterial infection, and short-term mortality in 162 consecutive patients with decompensated cirrhosis undergoing diagnostic paracentesis in a tertiary health care centre in Germany. MAIN OUTCOME MEASURE: Twenty-eight-day mortality. RESULTS: Circulating suPAR levels were increased in patients with decompensated cirrhosis and correlated with the severity of liver dysfunction and systemic inflammation but were not indicative of bacterial infection. Circulating suPAR levels >14.4 ng mL(-1) predicted 28-day mortality, even after adjustment for liver function and confounders [HR = 3.05 (1.35-6.90); P = 0.0076] equal to the MELD score (AUC = 0.71; 95% CI = 0.61-0.81; P < 0.001). Cut-off levels derived from cohorts without liver disease were not applicable due to the low specificity. AF suPAR levels were elevated during spontaneous bacterial peritonitis (SBP), but not during episodes in which bacteria or bacterial DNA was translocated into the ascites. AF suPAR levels correlated poorly with systemic suPAR but were associated with a more severe course of SBP and a worse outcome. In vitro experiments revealed that monocytes, and to a lesser extent neutrophils, secrete suPAR after Toll-like-receptor ligation, which led to rapid urokinase plasminogen activator receptor cleavage followed by increased synthesis. CONCLUSION: Blood and ascitic suPAR levels provide distinct, but relevant prognostic information on the severity of complications in patients with end-stage liver disease.

Emergence of spontaneous bacterial peritonitis due to enterococci - risk factors and outcome in a 12-year retrospective study.

BACKGROUND: Third-generation cephalosporins (TGC) constitute the empirical first-line therapy for spontaneous bacterial peritonitis (SBP). Hospitalisation, invasive procedures and use of antibiotics may challenge this concept due to an increase in enterococci and other TGC-resistant microorganisms. AIM: To determine prevalence, risk factors and outcome of ascitic fluid infections caused by enterococci. METHODS: All independent episodes of culture-positive ascitic fluid between 2000 and 2011 in a German tertiary centre were analysed retrospectively. RESULTS: Out of 244 positive ascitic fluid cultures, 90 episodes of monomicrobial SBP and 25 episodes of monomicrobial bacterascites (BA) in patients with decompensated cirrhosis were identified. Enterococcus spp. were isolated in 32 (28%) episodes. We noticed a profound increase in the frequency of enterococcal infection over the study period from 11% to 35% (P = 0.007). Univariate risk factors for enterococcal SBP/BA included nosocomial infection (OR = 4.56; 95% CI 1.90-10.97), previous use of antibiotics (OR = 5.63; 95% CI 1.81-17.49) and recent gastrointestinal endoscopy (OR = 3.17; 95% CI 1.33-7.54). Nosocomial infection (OR = 3.29; P = 0.011) and recent antibiotic therapy (OR = 3.88; P = 0.025) remained independent risk factors for enterococcal infection in multivariate logistic regression and these factors contributed also to the model when only SBP cases were considered. In subjects with monomicrobial SBP who were treated with TGC or ciprofloxacin, the probability of 90-day survival was 12% in enterococcal infection compared to 50% in non-enterococcal SBP (P = 0.022 in log-rank test). CONCLUSION: Because of the increasing prevalence of enterococcal spontaneous bacterial peritonitis and its poor prognosis when treated inappropriately, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with risk factors.