Increased incidence of Clostridioides difficile infections were documented in Bulgarian hospitals during COVID-19. WGS was performed on 39 isolates from seven hospitals during 2015-2022. Antimicrobial resistance and toxin genes were inferred from genomes. MLST profiles, cgMLST, and wgMLST phylogeny …

Clostridioides difficile infection (CDI), characterized by colitis and diarrhea, afflicts approximately half a million people in the USA every year, burdening both individuals and the healthcare system. C. difficile 630Δerm is an erythromycin-sensitive variant of the clinical is …

Background Postoperative delirium is considered a serious complication in elderly patients. Elderly patients often suffer from several concomitant diseases. The reduced physical condition can increase the risk of cardiac, pulmonary and neurocognitive complications during and after surgery. SARS-CoV-2 infection primarily affects the respiratory tract but can also damage other organ systems such as the heart and brain. Given the wide range of pulmonary, cardiac and neurocognitive complications caused by SARS-CoV-2, these risks must be given special consideration during planned surgical procedures. Both surgical procedures and anesthesia are risk factors for postoperative complications in themselves. The specific impact of prior SARS-CoV-2 infection on perioperative complications in elderly patients has not been sufficiently researched. The aim of this study is to understand how a previous SARS-CoV-2 infection influences the occurrence of perioperative complications. Methods In this case-control study, the data of patients over 60 years of age undergoing elective surgery are analyzed. Subjects are divided into two groups based on their SARS-CoV-2 infection status: those with a documented previous infection and those without. Confirmation of infection will be based on written evidence and anamnestic information. The primary endpoint of the examination is the occurrence of delirium within the first five postoperative days. In addition, further cardiac, pulmonary and neurocognitive complications are recorded in the perioperative period. The occurrence of postoperative delirium is recorded during the daily ward round in the first five days after the operation. The 3DCAM test and the 4AT are used for this purpose. In addition, the CAM-ICU will be used in the intensive care unit. The recruitment will include 266 patients. Statistical analyses will be performed to determine the correlation between a previous SARS-CoV-2 infection and the observed clinical outcomes. Discussion The results of this study will provide new insights into the impact of prior SARS-CoV-2 infection on perioperative complications in elderly patients undergoing elective surgery. Trial registration: Deutsches Register Klinischer Studien DRKS00034861 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study is financed from own funds. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has been approved by the Ethics Committee of the Ludwig-Maximilians- Universität München (LMU Munich). The ethics committee reviewed and approved the study protocol under the reference number 23-0552. Informed written consent was obtained from all participants involved in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes * 3DCAM : 3-dimensional confusion assessment method 4AT : alertness, attention, acute change and abbreviated mental test-4 ACE2 : angiotensin-converting-enzyme-2-receptors ALI : acute lung injury ARDS : acute respiratory distress syndrome ASA : American Society of Anesthesiologists’ Physical Status BDSG : Bundesdatenschutzgesetz (Federal Data Protection Act) BMI : body-mass index CARDS : COVID-19-associated Acute Respiratory Distress Syndrome COVID-19 : coronavirus disease 2019 CRP : C-reactive protein eCRF : electronic Case Report Form FiO2 : fraction of inspired oxygen GCP : good clinical practice GI : gastrointestinal ICU : intensive care unit KAS : Krankenhaus-Informations-und Verwaltungssystem (hospital information and administration system) LMU : Ludwig-Maximilians-Universität MAP : mean Arterial Pressure MOCA : Montreal Cognitive Assessment NarkoPrämed : Narkose Prämedikation (anesthesia premedication) NRS : numerical Rating Scale PaO2 : partial pressure of arterial oxygen PaCO2 : partial pressure of arterial carbon dioxide PCPF : Post-COVID pulmonary fibrosis PCR : polymerase chain reaction test PEEP : positive end-expiratory pressure Pmean : mean pressure PONV : postoperative nausea and vomiting Ppeak : peak pressure REDCap : research electronic data capture RKI : Robert Koch Institut SARS-CoV-2 : severe acute respiratory syndrome coronavirus 2 SpO2 : oxygen saturatios SSRI : selective serotonin reuptake inhibitor TIVA : total intravenous anesthesia VT : tidal volume

Importance Cardiovascular and renal consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been studied intensively in high-risk groups, but the consequences of mild infection for the general population, particularly beyond the acute phase of infection, remain unclear. Objective To examine long-term associations between SARS-CoV-2 infection and cardiovascular and kidney disease (CVD, KD) in the general population, with emphasis on age and vaccination status at the time of infection, mild infection, and SARS-CoV-2 variant. Design Register-based cohort study. Setting Denmark Participants All Danish residents with ≥1 PCR test for SARS-CoV-2 infection, March 2020-December 2022. Exposure Positive PCR test for SARS-CoV-2 infection. Main Outcomes Hazard ratios for 15 CVD outcomes and six KD outcomes, comparing persons testing positive for SARS-CoV-2 infection and persons who only ever tested negative for infection. Results The cohort for CVD analyses included 4,508,489 persons without pre-existing CVD (median follow-up 25.2 months/person, interquartile range [IQR] 21.7-27.5 months); 2,698,261 persons (59.8%) tested positive for SARS-CoV-2 infection during the study period. The cohort for the KD analyses included 5,150,480 persons without pre-existing KD (median follow-up 25.1 months, IQR 21.7-27.4 months), 2,983,233 (57.9%) of whom tested positive for infection. SARS-CoV-2 infection was associated with slight increases in the risks of pulmonary embolism, venous embolism/thrombosis, arrhythmias, chronic renal failure, unspecified renal failure, and other/unspecified KD up to a year after infection; infection was not associated with the other disease groups tested. The strongest associations between SARS-CoV-2 infection and CVD and KD were observed among unvaccinated persons and persons infected with earlier (pre-omicron) variants. Conclusions and Relevance We found little evidence that infection with SARS-CoV-2 was associated with increased long-term risks of CVD or KD in the general population. Increased CVD risks associated with SARS-CoV-2 infection appeared limited to three outcomes (pulmonary embolism, venous embolism/thrombosis, arrhythmias) and the potential increases in risk were small. Our KD results also suggested that any persistent risks associated with SARS-CoV-2 infection were minimal; however, these findings need to be confirmed in other populations. Most importantly, in a largely vaccinated population, long-term CVD and KD risks differed little for omicron-infected and uninfected persons. Question Does SARS-CoV-2 infection increase the long-term risks of cardiovascular disease (CVD) or kidney disease (KD) in a general population cohort with predominantly mild infection? Findings In a cohort study of 4.5 million persons that compared SARS-CoV-2 test-positive and test-negative persons, relative risks were slightly increased for 6 of 21 CVD and KD outcomes up to 1 year after infection. Among vaccinated individuals and omicron-infected persons, existing associations diminished dramatically. Meaning In the general population, long-term increases in CKD and KD risks associated with infection were small, limited to a few outcomes, and attenuated with vaccination and the omicron variant. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Lundbeck Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: By Danish law, studies based solely on data from the Danish national registers require neither informed consent nor approval from the Danish research bioethics committees. This study was authorized by the Department of Data Protection and Information Security at Statens Serum Institut under the terms of an agreement between Statens Serum Institut and the Danish Data Protection Agency governing the use of personal data in research. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data used in this study were retrieved from Danish national registers and do not belong to the authors but to the Danish Health Data Authority. The authors are therefore not permitted to make the data publicly available. However, upon receipt of approval from the Danish Data Protection Agency, data from the registers are available by applying to the Danish Health Data Authority via their online request system.

spaniClostridioides difficile/i is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin/span …

Treatment with antibiotics is a major risk factor for iClostridioides difficile/i infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit iC. difficile/i colonization include the conversion of conjugated primary bile salts in …

Many bacterial toxins exert their cytotoxic effects by enzymatically inactivating one or more cytosolic targets in host cells. To reach their intracellular targets, these toxins possess functional domains or subdomains that interact with and exploit various host factors and biological processes. Des …

Clostridioides difficile, a spore-forming anaerobic bacterium, is the primary cause of hospital antibiotic-associated diarrhea. Key virulence factors, toxins A (TcdA) and B (TcdB), significantly contribute to C. difficile infection (CDI). Yet, the specific impact of these toxins, particularly on ent …

Clostridioides difficile has rapidly become a major cause of nosocomial infectious diarrhea worldwide due to the misuse of antibiotics. Our previous study confirmed that RT046/ST35 strain is associated with more severe clinical symptoms compared to RT012/ST54 strain. We conducted genome comparison o …

C. difficile NAAT+/toxin- status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.

C. difficile infections impact thousands of individuals every year many of whom experience recurring infections. Clinical studies have reported an unexplained correlation between some clades / ribotypes of C. difficile and disease severity / recurrence. Here, we demonstrate that C. …

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The ...

Many patients with COVID-19 develop brain fog and other cognitive symptoms months later. Their cerebrospinal fluid may hold clues to why this is happening.

Many bacterial toxins exert their cytotoxic effects by enzymatically inactivating one or more cytosolic targets in host cells. To reach their intracellular targets, these toxins possess functional domains or subdomains that interact with and exploit various host factors and biological processes. Des …

Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune…

The panelist discusses how recurrent Clostridioides difficile infections involve complex differential diagnosis, including persistent infection, reinfection, and other gastrointestinal conditions. Definitive diagnosis requires molecular and immunological testing of stool samples to detect toxin genes and active toxin production.

Treatment with antibiotics is a major risk factor for Clostridioides difficile infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit C. difficile colonization include the conversion of conjugated primary bile salts in …

Among 547 episodes of C difficile infection documented in cancer patients in Australia and Spain, 50% were severe, and the 90-day recurrence rate was 16%

Corrigendum to "Clostridioides difficile infections were predominantly driven by fluoroquinolone-resistant Clostridioides difficile ribotypes 176 and 001 in Slovakia in 2018-2019" [International Journal of Antimicrobial Agents, 62 (2023) 1-9/106824]

Clostridioides difficile can transiently or persistently colonize the human gut, posing a risk for infections. This colonization is influenced by complex molecular and ecological interactions with the human gut microbiota. By investigating C. difficile dynamics in human gut communities over hundreds …

Clostridioides difficile, a spore-forming anaerobic bacterium, is the primary cause of hospital antibiotic-associated diarrhea. Key virulence factors, toxins A (TcdA) and B (TcdB), significantly contribute to C. difficile infection (CDI). Yet, the specific impact of these toxins, particularly on ent …

Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C. difficile have a range of clinical …

Clinical symptoms of Clostridioides difficile infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of C. difficile with higher rel …

We investigated the intra-hospital distribution of C. difficile strains by whole-genome sequencing (WGS) of isolates collected in 2022 at the University Hospital Centre (UHC) Zagreb. In total, 103 patients with first-episode CDI in 2022 at UHC Zagreb were included, based on the screening stoo …

Clostridioides difficile is an obligate anaerobic, Gram-positive bacterium that produces toxins. Despite technological progress, conducting gene expression analysis of C. difficile under different conditions continues to be labor-intensive. Therefore, there is a demand for simplified t …

PMC was characterized by a combination of diarrhea, intoxication and abdominal pain. The formation of PMC was preceded by courses of antibacterial drugs of the fluoroquinolone and cephalosporin groups, eradication therapy for iHelicobacter/i infection, the use of high doses of glucocorticosteroi …

Fetal growth restriction (FGR) is a common complication of pregnancy, which seriously endangers fetal health and still lacks effective therapeutic targets. Clostridium difficile (C. difficile) is associated with fetal birth weight, and its membrane vesicles (MVs) are pathogenic vectors. However, the …

CDI is important because of its frequent occurrence and potential for fatal outcomes. It is crucial to identify patients at risk for recurrence. In our study, the development of CDI attacks in the intensive care unit, malignancy, and continuation of antibiotic treatment for non-CDI infection after C …

We investigated the intra-hospital distribution of C. difficile strains by whole-genome sequencing (WGS) of isolates collected in 2022 at the University Hospital Centre (UHC) Zagreb. In total, 103 patients with first-episode CDI in 2022 at UHC Zagreb were included, based on the screening stoo …