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Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study.

ABSTRACT: Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient's response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts.

SUBMITTER: Filippidis P

PROVIDER: S-EPMC9267637 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundClostridioides difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. There is little available data regarding risk factors of CDI for patients who undergo cardiac surgery. The study evaluated the course of CDI in patients after cardiac surgery.MethodsOf 6,198 patients studied, 70 (1.1%) developed CDI. The control group consisted of 73 patients in whom CDI was excluded. Perioperative data and clinical outcomes were analyzed.ResultsPatients with CDI were significantly older in comparison to the control group (median age 73.0 vs 67.0, P = 0.005) and more frequently received proton pump inhibitors, statins, β-blockers and acetylsalicylic acid before surgery (P = 0.008, P = 0.012, P = 0.004, and P = 0.001, respectively). In addition, the presence of atherosclerosis, coronary disease and history of malignant neoplasms correlated positively with the development of CDI (P = 0.012, P = 0.036 and P = 0.05, respectively). There were no differences in the type or timing of surgery, aortic cross-clamp and cardiopulmonary bypass time, volume of postoperative drainage and administration of blood products between the studied groups. Relapse was more common among overweight patients with high postoperative plasma glucose or patients with higher C-reactive protein during the first episode of CDI, as well as those with a history of coronary disease or diabetes mellitus (P = 0.005, P = 0.030, P = 0.009, P = 0.049, and P = 0.025, respectively). Fifteen patients died (21.4%) from the CDI group and 7 (9.6%) from the control group (P = 0.050). Emergent procedures, prolonged stay in the intensive care unit, longer mechanical ventilation and high white blood cell count during the diarrhea were associated with higher mortality among patients with CDI (P = 0.05, P = 0.041, P = 0.004 and P = 0.007, respectively).ConclusionsThe study did not reveal any specific cardiac surgery-related risk factors for development of CDI.

Project description:Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils.IMPORTANCEClostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.

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Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study.

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